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Endometrial cancer in Asian migrants to the United States and their descendants

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Endometrial cancer in Asian migrants to the United States and their descendants

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Content ENDOMETRIAL CANCER IN ASIAN MIGRANTS
TO THE UNITED STATES AND THEIR DESCENDANTS
by
C. Katherine Liao
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(APPLIED BIOMETRY AND EPIDEMIOLOGY)
December 2000
Copyright 2000 C. Katherine Liao
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UMI Number: 1407918
___ ®
UMI
UMI Microform 1407918
Copyright 2002 by ProQuest Information and Learning Company.
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UNIVERSITY O F SO U T H E R N CALIFORNIA
TH E GRADUATE SC H O O L
UNIV ERSITY PARK
LOS A N G ELES. C A LIFO R N IA 8 0 0 0 7
This thesis, written by
C. K a th e r in e L ia o
under the direction of Thesis Committee,
and approved by all its members, has been pre
sented to and accepted by the Dean of The
Graduate School, in partial fulfillm ent of the
requirements fo r the degree of
Master of Science: Applied Biometry & Epidemiology
Dton
D ate Decem ber 1 8 , 2000
THESIS COMMITTEE
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TABLE OF CONTENTS
LIST OF TABLES................................................................................................................. iii
CHAPTER 1............................................................................................................................. 1
I n t r o d u c t io n t o E n d o m e t r ia l C a n c e r .......................................................................... 1
M ig r a n t S t u d ie s ............................................................................................................................. 2
SEER P r o g r a m .................................................................................................................................4
L it e r a t u r e R e v ie w o f R is k F a c t o r s.................................................................................5
CHAPTER 2........................................................................................................................... 11
M a t e r ia l s a n d M e t h o d s ......................................................................................................... 11
M is s in g D a t a ...................................................................................................................................12
E x c l u s io n a n d In c l u sio n C r it e r i a .................................................................................. 13
S t a t is t ic a l M e t h o d s...................................... 15
CHAPTER 3............................................................................................................................19
R e s u l t s ................................................................................................................................................19
CHAPTER 4........................................................................................................................... 22
D i s c u s s io n .........................................................................................................................................22
BIBLIOGRAPHY..................................................................................................................37
ii
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LIST OF TABLES
Table Page
1 Endometrial cancer cases in residents of Hawaii, San
Francisco/Oakland, and western Washington, aged 35-74 years, from
1973 to 1986.............................................................................................................. 11
2 Incidence of endometrial cancer in Asian Americans by race and
birthplace from 1973 to 1986 .................................................................................. 12
3 Epithelial Tumor cell-types eligible and included in US Analysis.......................... 14
4 Incidence of endometrial cancer among Asians, by race and country of
residence......................................................................................................................18
5 Summary of mean BMI in kg/m2, standard deviation in US Whites and
Asians born in US and Asia and residing either in US or native
homeland.................................................................................................................... 23
6 Summary of prevalence of postmenopausal estrogen use in the US and
A sia .............................................................................................................................30
7 Most common cancers in US women (Rates are “average annual” per
100,000 population, age-adjusted to 1970 U.S. standard)....................................... 35
8 SEER Incidence and Mortality Rates, 1988-1992 (Rates are “average
annual” per 100,000 population, age-adjusted to 1970 U.S. standard)....................36
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CHAPTER 1
In t r o d u c t io n t o E n d o m e t r ia l C a n c e r
Endometrial cancer is defined as having malignant cells in the lining of the uterus.
The uterus is the hollow, pear-shaped, female reproductive organ where a fetus grows.
Cancer of the endometrial lining is different from cancer of the muscle of the uterus,
sarcoma, and from cancer of the cervix, which is portion of the uterus which protrudes
into the vaginal canal.
Research efforts in endometrial cancer could focus on several aspects: early
detection, etiology/causative factors, or treatment. Unfortunately, good screening/early
detection programs for endometrial carcinoma are lacking. Past attempts include a
comprehensive New York study to determine whether precursor stages of endometrial
cancer could be identified. This study concluded that the process of endometrial cancer
detection is a complex and costly process that could be the greatest benefit to women
“particularly prone to develop endometrial carcinoma based on epidemiologic
characteristics” rather than asymptomatic women (Koss et ah, 1981).
Researching epidemiologic characteristics or risk factors for endometrial cancer
has become promising due to the varying incidence of endometrial cancer in different
parts of the world. High endometrial cancer rates occur in North America and Northern
Europe; intermediate in Latin America, Southern Europe and Israel; and low in Asia and
Africa (Lumbiganon, 1994). Different incidence rates lead to an assessment of differing
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population characteristics, thereby providing etiologic clues to this particular female
reproductive cancer.
M ig r a n t S t u d ie s
Malignancies occur at various incidence levels in different regions of the world.
Within an individual country, there are even varying cancer rates among subpopulations.
Interestingly, individuals who move from one region of the world to another provide an
excellent means to investigate the etiology of cancer. These individuals are migrants who
came from their homeland/country of origin/ birthplace and established residence in their
new country of adoption. Migrants is the term referring to first-generation nationals, and
descendants o f migrants refers collectively to their offspring and subsequent generations.
The migration of human populations is an excellent means of studying the
respective roles of genetic versus environmental factors in cancer epidemiology. The
fundamental question, of whether differing incidence of specific diseases in separate
populations is due to the genetic composition of one population, or is due to living in
different environments involving different food habits, customs and working conditions,
can be addressed. Migration of populations is an excellent opportunity to observe an
unplanned, large-scale experiment on the etiology of cancer, thus providing vital clues to
the causation of disease. The genetic characteristics remain unchanged for migrants, but
their new environment may differ greatly from their homeland. Comparison of migrant
disease incidence, with that of their homeland kin is a means of studying genetically
similar groups under different environmental conditions. Climate, altitude, air quality,
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humidity, temperature, amount of solar and other types of irradiation are environmental
factors that may differ immediately from their homeland. These factors, in turn, affect
food and water supply resulting in variation in food choices. Cultural change in choice of
food and culinary practice can effect the migrant, as well as the subsequent generation.
Having left their native homeland, migrants conceivably become exposed to different
occupational exposures, sanitary habits, and economic levels.
Also, comparison of migrants with native residents of their newly adopted country
provides insight into two genetically different groups living in the same environment.
Information about lifestyle and exposure changes of migrants may help to develop and
confirm hypotheses about etiology. Rates of disease occurrence in migrants can be
uniquely compared with both rates occurring in their homeland and with rates of the new
country of adoption. These comparisons often yield migrant rates that either depart from
those of their homeland (thereby approximating those of the new country of residence) or
continue to correspond with rates of their homeland. Understandably, when migrant rates
of disease advance towards the incidence rate of the natives of their newly adopted
country, strong considerations are given to environmental factors, especially those related
to adaptations and changes in habits/lifestyles. In contrast, if disease rates of migrants
remain the same as their homeland residents, then elements of their genetic makeup or
cultural habits can be a possible causal or protective factor in the occurrence of the
particular disease.
Our study will include only three ethnic Asian groups: Chinese, Japanese, and
Filipinos. These three groups have historically emigrated to the United States (US)
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beginning in the mid-1800s and have a large population of US-bom descendants (Thomas
& Karagas, 1996). The Chinese emigrated to the US in large numbers as laborers from the
1850s until 1882. Until 1943 only a limited number of Chinese were permitted to enter the
US, but since 1968 large number of Chinese have been allowed to immigrate. The Japanese
also migrated to the US as laborers from the 1880s to 1924. Between 1924 and 1943
immigration of the Japanese was prohibited due to the US’ exclusionary legislation.
Similarly, Filipinos migrated to the US in large numbers as laborers from 1910 to 1934.
The next influx from the Philippines occurred after World War II, and this immigration
mainly involved Filipino men who served in the US Armed Forces. Large numbers of
Filipinos immigrated to the US after 1968 (Thomas & Karagas, 1996).
SEER P r o g r a m
Our migrant study will be based on newly diagnosed endometrial cancer cases
from the 1973-1986 portion of the Surveillance, Epidemiology, and End Result (SEER)
Program. The SEER Program is a population-based cancer registry started by National
Cancer Institute (NCI) in 1973, as a fulfillment to the National Cancer Act of 1971. The
Act mandated the collection, analysis, and dissemination of all data useful in the
prevention, diagnosis, and treatment of cancer.
In 1973-1986 the SEER Program collected data from thirteen areas in the United
States and its territories. Initiating on January 1, 1973, the original eight reporting areas
included Connecticut, Detroit, Hawaii, Iowa, New Mexico, Utah, San Francisco/Oakland,
Commonwealth of Puerto Rico. The following year, New Orleans, Seattle/Puget Sound,
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Atlanta were added. Both Arizona and New Jersey were added in 1980 and 1983,
respectively. The population and ethnic composition differ from one SEER geographic
area to another. With this in mind, our study is centered around three of the thirteen
reporting SEER areas from 1973-1976. The Hawaii, San Francisco/Oakland, and
Seattle/Puget Sound SEER registries were chosen because of their high Asian residency.
Collectively, these three SEER registries were used to calculate reliable cancer rates to
determine whether the incidence of endometrial cancer varies between US whites, Asians
bom in the US, and Asians residing in the US but bom outside of the US (migrants).
L it e r a t u r e R e v ie w o f R is k F a c t o r s
Menstrual Factors
The age at menarche in relation to endometrial cancer has been investigated and
has resulted in no consistent associations. Although earlier age at menarche has been
associated with increased risk for endometrial cancer in several studies (Brinton et al.,
1992; Kelsey et al., 1982; La Vecchia et al., 1984), other studies reported no differences
(Mack et al., 1976; Spengler et al., 1981; Wynder et al., 1966). With the exception of
one study (Brinton et al., 1992), the later in life a woman begins menopause the greater
the risk of endometrial cancer (Elwood et al., 1977; Kelsey et al., 1982; Spengler et al.,
1981; Stavraky et al., 1981; Wynder et al., 1966). A menstruating woman in her fifties
continues to produce estrogen in her functioning ovaries, which can be indicative of
inadequate opposing progesterone (Voigt & Weiss, 1989).
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Reproductive Factors
The uterus, a sex hormone-dependent organ, responds normally to changing levels
of estrogen and progesterone throughout a woman’s reproductive life. Fluctuation of
these two hormones occur naturally within menstrual cycles and during pregnancy.
Infertility due to progesterone deficiency or anovulation, increased a woman’s risk of
endometrial cancer by a 3.5-fold in one case-control study (Henderson et al., 1983). In
another study, nulliparous women seeking medical advice for infertility had a
significantly elevated risk compared with nulliparous women who had no difficulty
conceiving (Brinton et al., 1992). Nulliparity has consistently increased a woman’s risk
of endometrial cancer by two- to threefold (Brinton et al., 1992; Kelsey et al., 1982; La
Vecchia et a l, 1984; Parazzini et al, 1991). Additional studies have shown that a
woman’s probability of developing endometrial cancer is negatively associated with the
number of children she has borne (Elwood et a l, 1977; Kelsey et a l, 1982; Spengler et
a l, 1981; Wynder et a l, 1966). Surprisingly, early age at first birth has not been found to
reduce endometrial cancer risk, as has been found for breast cancer (Brinton et a l, 1992;
Elwood et al, 1977; Lesko et a l, 1991). However, late age of last birth may reduce risk.
The risk for women whose last delivery occurred after age 35 or 40 has been found to be
about half that of women whose last delivery occurred before age 20 or 25 (Lesko et a l,
1991; Parazzini et a l, 1991).
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Other Risk Factors
Diabetes
Most studies examining the relationship between diabetes and endometrial cancer
were conducted in the 1970s, and most of these observed a positive association (Grady &
Ernster, 1996). Interpretations of studies regarding this relationship were mixed. Non
significant findings were reported by Mack et al (1976), Elwood et al (1977), Kelsey et al
(1982) with the odds ratio of 2.3 (not significant, no specific p-value reported), 2.3 (95%
Cl 0.9-5.8), and 1.3 (95% Cl 0.7-2.3), respectively. An increased risk for diabetic women
was shown in studies conducted by Hoogerland et al (1978), La Vecchia et al (1986),
Brinton et al (1992) with odds ratio of 2.1 (p<0.001), 2.77 (95% Cl 1.61-4.75), and 1.95
(95% Cl 1.1-3.6), respectively. The increase in risk of endometrial cancer among women
with diabetes has been observed, but this increase may be in part explained by obesity
(Kelsey et al., 1982).
Hypertension
Like diabetes, hypertension has been more frequently reported among women
with endometrial cancer. However, this association has been difficult to ascertain because
of difficulties in retrospective assessment of blood pressure and because many studies had
not adjusted for confounding effects of body weight and estrogen. Kelsey et al. (1982)
and Mack et al. (1976) have shown that the increased risk for endometrial cancer among
hypertensive women may be due to obesity or to estrogen use. In a study that controlled
for the potential confounding variables of parity, estrogen use, and recent weight gain,
there was no increase in risk with hypertension (Brinton et al., 1992). It is unclear
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whether any true causal relationship exists when controlling for parity, estrogen use, and
body weight (Voigt & Weiss, 1989).
Gallbladder Disease
Two studies (Hulka et al., 1980; Spengler et al., 1981) found a greater proportion
of women with prior gallbladder disease among endometrial cancer cases than among
controls. Among the cases, 17.7 percent had gallbladder disease whereas only 12.3
percent of the community controls had gallbladder disease in the North Carolina study
(Hulka et al., 1980). In the Canadian study, Spengler (1981) found a statistically
significant difference between 29 percent of the cases having gallbladder problems
compared to 17% controls (p<.05). An earlier study conducted by Mack (1976) found a
statistically significant increase in risk of 3.7 times (95% confidence interval did exclude
1.0 according to the author) in those having gallbladder disease; but the same study found
that upon matching on estrogen use, the risk ratio for gallbladder disease was no longer
significantly associated with endometrial cancer. This association and increased risk does
not persisted in studies that controlled for estrogen use, body weight, as well as other risk
factors. The excess risk of endometrial cancer associated with gallbladder disease was
not statistically significant 1.41 (95% Cl 0.8-2.3) in Brinton’s study (1992), which
adjusted for age at interview, years of education, number of births, oral contraceptive use,
menopausal estrogen use, and weight gain.
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Smoking
An overwhelmingly large number of studies consistently observe a protective
effect of smoking (Grady & Ernster, 1996). A population- and hospital-based case-
control study of endometrial cancer and cigarette smoking behavior indicated a
significant relative risk of 0.5 and noted a lower proportion of smokers among cases than
among controls (Franks et al., 1987; Lesko et al, 1985; Stockwell & Lyman, 1987; Weiss
et al., 1980). Differential estrogen metabolism occurs among smokers, producing a
metabolite of low estrogenic activity (2-hydoxyestrone) (Michnovicz et al., 1986). Also,
smokers have been shown to have decreased levels of serum estrogen (Jensen et al.,
1985).
Genetic and Family History
Only a few studies have addressed the question of whether women with a family
history of endometrial cancer are at increased risk for the disease. Evidence supporting
an association includes a hospital-based case-control study that found an increased risk
for women whose mothers or sisters had a history of endometrial or ovarian cancer
(Kelsey et al., 1982). If an association exists, it is likely to be weak and accounts for a
small fraction of endometrial cancer cases (Voigt & Weiss, 1989).
Factors of Interest for the current study
We will attempt to explain our findings by focusing on the risk factors of obesity
and use of postmenopausal estrogens. The different dietary habits of Asians and US
whites may influence the extent of obesity in these respective populations. High body
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weight and obesity put women at greater risk for endometrial carcinoma (Elwood et al.,
1977; Henderson et al., 1983; Hoogerland et al., 1978; Hulka et al., 1980; Kelsey et al.,
1982; La Vecchia et al., 1984; Mack et al., 1976; Parazzini et al., 1991; Swanson et al.,
1993; Weiss & Sayvetz, 1980; Ziel & Finkle, 1975). Hormone replacement therapy
(HRT) is used more frequently in Europe and North America because postmenopausal
osteoporosis is a major cause of morbidity and mortality in these areas. Approximately 40
percent of postmenopausal women in the US experience osteoporotic fracture by the end
of their life, and therefore use of long-term HRT to increase bone mass is common
(Eriksen et al., 1996). Unfortunately, postmenopausal women who use estrogens are at a
greatly increased risk of developing endometrial cancer (Mack et al., 1976; Shapiro et al.,
1980; Smith et al., 1975; Weiss et al., 1979; Ziel & Finkle, 1975).
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CHAPTER 2
M a t e r ia l s a n d M e t h o d s
This study focused on three specific SEER geographic areas of Hawaii and San
Francisco/Oakland registries for 1973-1986 and western Washington State for 1974-
1986. Qualifying cases had to be invasive cancer involving the primary site of corpus
uteri, including the isthmus (ICD-0 codes 820 and 821). A total of 879 Asians and
11,642 Whites are included in our endometrial cancer analysis (Table 1).
A special tabulation from the 1980 US Bureau of Census’ population for the three
SEER areas in with regard to age, race, and birthplace provided estimates for our
TABLE 1
Endometrial cancer cases in residents of Hawaii, San
Francisco/Oakland, and western Washington, aged 35-74 years, from
1973 to 1986
CHINESE JAPANESE FILIPINO WHITE
Total 256 480 143 11,642
Exclusions
Diagnosed on death certificate 0 0 0 17
First diagnosed at autopsy 0 0 0 15
No histologic confirmation 1 0 0 18
Excluded cell-type 20 32 11 505
Subjects /available for analysis 235 448 132 11,087
Birthplace
US 97 368 32 7,434
Asian "homeland" 90 24 83 —
Other 6 1 1 1,027
Unknown 42 55 16 2,626
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population at risk. The age and race distributions were based on the census of the
population. Place-of-birth estimates were based on a combined random sample of: one-
half of all housing units in counties, incorporated regions, and minor civil division having
fewer than 2,500 persons, and one-sixth of housing units in all other areas. As a result,
19 percent of the households in the three SEER areas were used to determine birthplace.
M is s in g D a t a
The analysis of endometrial cancer incidence in Asian Americans (Table 2)
involved calculating rates categorized by race and place o f birth. There was a substantial
number of cases in our study that were missing information on place o f birth (Table 1).
Unlike other epidemiologic studies of incidence of disease where subjects with missing
data are excluded from a study, our analysis included these subjects, because discarding
TABLE 2
Incidence of endometrial cancer in Asian Americans by race and
birthplace from 1973 to 1986
RACE BIRTHPLACE No. RATE3 RATE RATIO” 95% Cl
Chinese US 97 57.2 0.74 0.60-0.91
China 90 42.6 0.55 0.39-0.78
Japanese US 368 51.2 0.67 0.57-0.78
Japan 24 25.3 0.33 0.20-0.54
Filipino US 32 24.5 0.32 0.21-0.48
Philippines 83 27.4 0.36 0.28-0.45
3 Annual rate per 100,000 among persons aged 35-74 years, adjusted to the
distribution of age (five-year groups) and area of residence for the combined
Asian population of the three SEER areas.
b Relative to that of US-born whites aged 35-74 years.
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the subjects with unknown birthplace would have had a noticeable effect on the
magnitude of rate estimates. The method used to handle missing place o f birth data was
to assume that participants without a recorded birthplace, have the same birthplace
distribution, as those participants with complete information on birthplace and who were
of the same ethnicity, sex, and SEER area. Directly standardized incidence rates were
calculated and did account for those patients with unknown birth origin.
E x c l u s io n a n d I n c l u sio n C r it e r ia
Comparison among US residents
The 1973-1986 SEER data on endometrial cancer provided the following case
total: 11,642 US Whites and 815 Asians who were migrants to the US or US-born (256
Chinese, 480 Japanese, and Filipino 143) (Table 1). This analysis will be referred to as
the “US Analysis” and was restricted to cancer cases from the three SEER regions of San
Francisco-Oakland, western Washington, and Hawaii with the following criteria:
• of adults aged 35 to 74 years,
• not diagnosed on the death certificate,
• diagnosed with endometrial cancer prior to autopsy,
• histologic-confirmed carcinoma, and
• endometrial cancer of the epithelial cell-type (Table 3).
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TABLE 3
Epithelial Tumor cell-types eligible and included in US Analysis
Epithelial Tumors ICD-Oa
Adenocarcinoma
Papillary carcinoma, NOS 8050
Adenocarcinoma 8140
Scirrhous adenocarcinoma 8141
Superficial spreading adenocarcinoma 8143
Adenocarcinoma in adenomatous polyp 8210
Papillary adenocarcinoma, NOS 8260
Villous adenocarcinoma 8262
Mixed cell adenocarcinoma 8323
Endometriod carcinoma 8380
Cystadenocarcinoma 8440
Papillary serous Cystadenocarcinoma 8460
Papillary serous Cystadenocarcinoma 8461
Mucinous adenocarcinoma 8480
Mucin-producing adenocarcinoma 8481
Adenocarcinoma with squamous metaplasia 8570
Adenocarcinoma with apocrine metaplasia 8573
Clear cell
Clear cell adenocarcinoma 8310
Mesonephroma, malignant 9110
Squamous cell
Papillary squamous cell carcinoma
Q A C T
O V Jii
Squamous cell carcinoma, NOS 8070
Squamous cell carcinoma, keratinizing type, NOS 8071
Squamous cell carcinoma, large cell, non-keratinizing type 8072
Adenosquamous
Adenoid squamous cell carcinoma 8075
Adenosquamous carcinoma 8560
Undifferentiated
Carcinoma, undifferentiated type, NOS 8020
Carcinoma, anaplastic type, NOS 8021
Giant cell and spindle cell carcinoma 8230
Medullary Carcinoma 8510
Unclassified and Other
Malignant tumor, small cell type 8002
Malignant tumor, giant cell type 8003
Carcinoma, NOS 8010
Large cell carcinoma
8012
Pleomorphic carcinoma 8022
Giant cell and spindle cell carcinoma
8030
Spindle cell carcinoma
8032
Small cell carcinoma
8041
Carcinoma, diffuse type 8145
international Classification of Disease codes of neoplasm morphology
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After including only the subjects that fit the above criteria, the number of subjects
incorporated in our analysis included 11,087 US Whites, 235 Chinese, 448 Japanese, and
143 Filipino. Of the Chinese women in our study, approximately half were in the US and
the other half born in Asian “homeland.” The majority of the Japanese were US-born
(n=368, 82 percent), whereas most of the Filipinos had a birthplace of their homeland
(n=83, 63 percent).
Comparisons between US residents and Asians residing outside of US
The second analysis, “World Analysis,” compared incident endometrial cancer
rates of Asians residing in the US with Asians residing in China, Hong Kong, Singapore,
Japan, and the Philippines. The World Analysis had very few restrictions and included
all ages, all cell-types, and did not exclude on the basis histologic-confirmation or type of
diagnosis. A less stringent and broad inclusion criteria for the World analysis was
necessary in order to compare the SEER data with world incidence rates provided by
Cancer Incidence in Five Continents (Muir et al., 1987; Parkin et al., 1992).
S t a t is t ic a l M e t h o d s
An initial raw data file contained all diagnoses of cancer of the uterine corpus
from all nine SEER registries (1973 -1986) with 44,182 cases. Initially the SEER data set
was in ASCII file format. The analytical and spreadsheet package-SPSS was used to split
files, create new variables, sort, and produce subsets of the data. After manipulations with
SPSS, the Migrant Cancer Incidence Analysis (MCIA) Program was used.
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Migrant Cancer Incidence Analysis is a PC-DOS/MS-DOS compatible software
designed to calculate adjusted incidence rates and associated statistics for populations of
different race-place of birth combinations, using data from the National Cancer Institute’s
SEER Registry and the US Census Bureau. This program is capable of calculating
birthplace and race-specific incidence rates and rate ratios.
Summary Incidence Rate Calculations
Direct adjustment for both age and SEER site was used to calculate summary
incidence rates for homeland-born and US-bom Chinese, Japanese, and Filipinos.
Adjusted rate ratios along with their 95% Confidence Intervals (95% Cl) were calculated
by comparing the adjusted incidence rate for each ethnicity of migrants and their
descendants with the adjusted incidence rate for US-born Whites (Table 2). Specifically,
the numerators of the rates were the number of patients of each ethnicity who were either
born in the homeland or US, while the denominators were the number of persons of the
same ethnic group who were bom in the corresponding homeland or US and resided in
the three SEER areas multiplied by the number of years the registry had been in
existence. The ‘Homeland’ areas for the Asian descendants in this study were China,
Hong Kong, or Singapore for the Chinese; Japan for the Japanese, and Philippine Islands
for the Filipinos. The rates for US-born Whites residing in the three SEER areas were
also calculated and utilized for the rate ratios (Table 2). The three combined Asian
populations of the three SEER areas were used as the standard populations.
Similarly, during comparison with rates in Asia, a direct method with adjustment
for age was used to calculate summary incidence rates for 1973-1986 US-bom and
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Homeland born Chinese, Japanese, and Filipinos (Table 4). All corpus uteri cases were
included as incident cases. The age distribution of the world was used as a standard in
this analysis.
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TABLE 4
Incidence3 of endometrial cancer among Asians, by race and country of
residence.
INCIDENCE
CHINESE
US 1973-1986
US-born 9.2
Foreign-born 8.7
Quidong City 1983-1987 0.4
Shanghai 1978-1982 4.0
1983-1987 2.9
Tianjin 1981-1982 3.5
1983-1987 2.8
Hong Kong 1978-1982 6.3
1983-1987 6.9
Singapore (Chinese) 1978-1982 4.2
1983-1987 6.4
JAPANESE
US 1973-1986
US-born 12.8
Foreign Bom 5.3
Hiroshima 1978-1980 4.1
1981-1985 4.9
Miyagi Prefecture 1978-1981 3.6
1983-1987 3.2
Nagasaki 1978-1982 3.6
1983-1987 2.9
Osaka Prefecture 1979-1982 2.6
1983-1987 2.7
Saga Prefecture 1984-1986 2.4
FILIPINO
US 1973-1986
US-born 3.5
Foreign Born 6.4
Manila 1983-1987 6.3
Rizal Province 1978-1982 1.8
1983-1987 5.5
3 Annual rate per 100,000 adjusted to the distribution of age (five-year groups) to the
world standard population. Persons of all ages included.
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CHAPTER 3
R e s u l t s
Comparisons among US residents
US-born Chinese have the highest rate of endometrial cancer (57.2/100,000)
among all Asians in the study (Table 2). Those Chinese residing in the US but were bom
outside of the US had a lower incidence (42.6/100,000) than their US-born counterparts.
The incidence (51.2/100,000) in Japanese-Americans is considerably higher than Japan-
born Japanese (25.3/100,000). US-born Filipinos had a slightly lower incidence rate
(24.5/100,000) than Philippine-born Filipinos residing in the US (27.4/100,000). The
US-born Chinese and Japanese had higher rates of endometrial cancer than native-born
Asian, and this approaches the high incidence rates of US White females (77.0/100,000).
The rate ratios of both Chinese and Japanese who were bom in their native
homeland but residing in the US, were 0.55 and 0.33 compared with US Whites,
respectively. Their descendants, US-born Chinese and Japanese, had an increasing
incidence of endometrial cancer from two-thirds to three-quarters of the rates of US
whites. The rate ratios of 0.74 for US-born Chinese and 0.67 for US-born Japanese,
indicate a rise in risk which is closer to the high rates of endometrial cancer in US
Whites. On the other hand, Filipino women had about one-third the endometrial cancer
incidence rates of US Whites, irrespective of place of birth. The rate ratios for Filipino
19
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women born in the Philippines and residing in US was 0.36 and for US-born Filipino
women was 0.32, compared to US Whites.
Comparisons among residents of Asia and the US
Asian-Americans of Chinese descent, whether born in the US or homeland, had
similar or higher rates of endometrial cancer than Chinese in Asia (Table 4). The 1973-
1986 incidence rates for the Chinese residing in the US had an age-adjusted annual rate of
9.2/100,000 if they were bom in the US and 8.7/100,000 if they were born in China,
Hong Kong, or Singapore. Chinese-Americans, irregardless of birthplace, have a far
higher incidence of endometrial cancer than Chinese residing in the cities of China, Hong
Kong, or Singapore. The Chinese remaining in their homeland or in the Eastern
hemisphere had relatively low incidences of 0.4 to 6.9/100,000 (Muir et a l, 1987; Parkin
e ta l, 1992).
Japanese descendants born in the US had substantially higher rates (12.8/100,000)
of endometrial cancer than both foreign-bom Japanese residing in the US (5.3/100,000)
and Japanese residing in Japan. Japanese residing on their native island have low rates
ranging from 2.4 to 4.9/100,000, which is less than half the rate of those Japanese who
chose to migrate to the US.
Both Japanese and Chinese born in the US have higher rates of endometrial cancer
(12.8 and 9.2/100,000) which are similar to US Whites rates of 15.6/100,000. However,
Filipinos born in the US had lower incidence (3.5/100,000) than Filipinos living in
Manila (6.3/100,000) and Rizal Province during the years 1983-87 (5.5/100,000).
20
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Filipino women who were foreign born but resided in the US, had an incidence rate
which was similar to incidence of Filipinos in the Philippines (6.4/100,000).
21
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CHAPTER 4
D is c u s s io n
Obesity
A likely explanation for the variation in endometrial cancer risk is a different body
mass index for US Whites, US-born Asians, and Asians born in their homeland. Obesity
and excess body weight are associated with an increase in the risk of endometrial cancer
(Grady & Ernster, 1996). An increasing level of BMI was associated with an increased
risk of endometrial cancer in Levi’s (1992) study on body mass index (BMI measured in
kg/m2). The multivariate relative risk was 1.4 (95% Cl 1.0 to 2.1) for moderately
overweight women, BMI = 25-29, and 2.5 (95% Cl 1.3-5,1) for severely obese women,
BMI >=30 (Levi et al., 1992). Consistent, positive, and independent associations exist
between body weight or body mass index, weight gain, and various measures of central
adiposity and the risk of endometrial cancer. Increases in relative risks of 2-3.5 are
reported for women with BMI >= 28-30 (Ballard-Barbash & Swanson, 1996).
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The body mass indices for female populations in our study, which includes US
Whites; US-born Asians; Asians residing in the US but born in their native homeland;
and Asians living in Asia, are presented in Table 5. Overall, US whites have the greatest
BMI, and approximately one-third of all United States adults are overweight (Kuczmarski
et al., 1994). Between NHANES II (1976-1980) and NHANES III phase 1 (1988-1990),
the greatest increase (8 percent to 9 percent) in prevalence of overweight was observed in
TABLE 5
Summary of mean BMI in kg/m2, standard deviation in US Whites and
Asians born in US and Asia and residing either in US or native
homeland
Study Whites US-born
Asians
Asians residing in
the US but born in
native homeland
Asians
residing in
Asia
Akan (1995) 21.57,2.38 21.03, 1.91
Fujimoto
(1991)
23.1,0.5
(Japanese)
Huang (1996) 23.38,3.55
(Japanese)
23.05,3.51
(Japanese)
Kuczarski
(1994)
Kin (1993)
26.2, 0.15
age-adjusted
26.0
23.5,3.5
(Japanese)
22.0, 2.5
(Japanese)
21.8,2.7
(Japanese)
L ee(1994) 22.2, 0.2
(Chinese)
20.9, 0.1
(Chinese)
Popkin (1995) 21.9,2.8
(Chinese)
Wang (1994) 23.9,3.4 22.5,3.3
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Whites compared to other ethnicity living in the US. Futhermore, the age-adjusted
prevalence of overweight was higher in the NHANES 1988 to 1991 survey than in the
previous three surveys, with statistically significant differences (p < .01) (Kuczmarski et
al., 1994).
On the basis of 1990 population estimates, women comprise 32 million of the 58
million overweight US adults. The mean BMI by the NHANES I (1971-1974), NHANES
II (1976-1980), and NHANES III phase 1 studies (1988-1991) for women 20-74 has been
increasing from 24.9 to 25.1 to 26.3, respectively (Kuczmarski et al., 1994). The
Morbidity, Mortality Weekly Report (1997) documents 36 percent of US women as
having been overweight in the NHANES III survey (1988-94).
Whites were significantly taller, heavier, and had higher BMIs than Asians in a
New York City area study of 687 healthy volunteers aged 18-94. The study included 445
whites of European origin and 242 Asians (225 Chinese, 9 Japanese, 6 Koreans, and 2
Filipinos) (Wang et al., 1996). Ethnicity was defined by background of both parents and
all grandparents. Of the Asians, 97 percent were born in Asia. Among the female
participants, the 258 whites had a mean BMI of 23.9 and the 132 Asians had a mean BMI
of 22.5, which was significantly different from white females (p=0.002) (Wang et al.,
1996). In another study comparing four ethnic groups living in the New York City area,
the trend in BMI for the females in this study was Puerto Rican>black>white>Asian
(p<.01) (Wang et al., 1996). White females (n=309) had a mean BMI of 23.3 kg/m2. All
enrolled Asians were bom in Asia and had lived in the US from 6 months to 50 years
(n=144) and had a mean BMI of 22.0 kg/m2 (Wang et al., 1996).
24
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It would be useful to determine whether movement to the United States results in
a higher body mass index for Asian immigrants and their descendents. While 840
Japanese-Americans (aged 52-99) living in Hawaii had a mean BMI of 23.38 kg/m , 802
Japanese women enrolled in the same study (aged 50-88) but living in Hiroshima had a
mean BMI of 23.05 kg/m2 (Huang et al., 1996). Another study investigating the
prevalence of central adiposity among different populations compared physical
characteristics of Japanese women in the US and in Japan. The comparison showed that
US-bom Japanese-American women were heavier and taller then native Japanese women.
The US-bom Japanese Americans (JA) had a mean BMI of 23.5 kg/m2, which was greater
than the mean BMI of 22.0 kg/m2 found in Japan-born immigrant to the US (JB), which is
further greater than Native Japanese women (NJ) 21.8 kg/m2. This study found that the
BMI of JA was significantly different from both JB and NJ group (p<.05) (Kin et a l,
1993). Additionally, US-born Japanese-American women had a significantly higher
amount of body fat than immigrant Japanese-American women. Continuing the trend, the
immigrant women living in the US had a higher amount of body fat than their Japanese
counterparts living in their native land. In all instances, US-bom Japanese-Americans
weighed the most and had highest percentage body fat and greatest BMI among the three
Japanese study populations. The lifestyle and dietary changes related to body weight were
more apparent in US-born Japanese-Americans, while Japan-born immigrants had
remained similar to Japanese living Japan (Kin et a l, 1993). The author concluded that
U.S.-born Japanese-American women were heavier and taller than homeland-born
25
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Japanese women. Japanese and other ethnic groups are prone to gain weight with
increased urbanization and westernization (Fujimoto et al., 1995).
Lee et al (1994) found differences in body size, self-reported dietary nutrient
intakes, and physical activity patterns between 2,488 healthy Chinese men and women
residing in North America (US and Canada) and in the People’s Republic of China. The
Chinese in China weighed less (mean BMI 20.9 kg/m2 ) than North American Chinese
(22.2 kg/m2 ). North American Chinese were less physically active and had a greater body
mass index than Chinese in China, perhaps explaining why Chinese in Western countries
exhibit higher rates of many chronic diseases than do Chinese in Asia (Lee et al., 1994).
Results from China’s 1991 Health and Nutrition Surveys also reported a mean BMI of
21.9 kg/m2 for women 20-45 years old (Popkin et al., 1995). In contrast, US white
women aged 20-74 years old (1988-1991) had a mean BMI of 26.1 kg/m2 (Kuczmarski et
al., 1994). The trend toward increased BMI in US-bom Asians suggests that diet and
life-style changes may contribute to increase in body mass when compared to their Asian
counterparts living in their native Asian homeland. This increase in BMI aligns them
closer to weights of US white women. In a study of 98 female college students (36
African-Americans, 34 Asian-Americans, and 28 Caucasians), Caucasians had a mean
BMI of 21.57 kg/m2 , whereas Asian-Americans 21.03 kg/m2 (Akan & Grilo, 1995).
Among postmenopausal women, serum concentrations of progesterone and
estrogen decline dramatically, since the ovaries no longer actively produce sex hormones.
In overweight postmenopausal women, the adipose tissue’s estrogen production
predominates, resulting in prolonged exposure to more biologically active forms of
26
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estrogen (Ballard-Barbash & Swanson, 1996). Obese women have large quantities of
aromatase in their adipose tissue. The biologic mechanism by which obesity increases the
risk for endometrial cancer is probably through increased aromization of plasma
androstenedione to estrone in adipose tissue (Kelsey et al., 1982). Also, the mitotic rate
of endometrial cells increases when estrogen is unopposed by progestin, thereby
increasing the risk of endometrial cancer in obese postmenopausal women. Among
premenopausal women, obesity has been associated with an increased frequency of
anovulatory menstrual cycles and a concomitant decrease in progesterone (Swanson et al.,
1993). Without adequate levels of progesterone during the luteal phase of the menstrual
cycle, endometrial cells would be expected to proliferate and divide for a longer period,
compared with what normally occurs during an ovulatory cycle (Hill & Austin, 1996).
Excess weight throughout adult life would be expected to increase the duration of
exposure to unopposed estrogen (Swanson et al., 1993). High BMI and obesity result in
an increased risk of endometrial cancer in pre- and post-menopausal women by increasing
the levels and availability of endogenous oestrogens (Levi et al., 1992). The increased
BMI in US-bom Asians can place them at a higher risk for endometrial cancer than their
counterparts who remained in their Asian homelands (Table 5).
Postmenopausal Estrogen Use
Risk
Another major factor in the etiology of endometrial cancer is a woman’s exposure
to unopposed estrogens (Voigt & Weiss, 1989). Women take postmenopausal estrogen to
relieve hot flashes, vaginal dryness, and other symptoms of menopause (Chung et al.,
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1996). Estrogen therapy can also provide other health benefits, such as osteoporosis and
cardiovascular disease risk reduction (Beresford et al., 1997). Although the later two
conditions are prevented, a significant positive association between the use of estrogen
replacement therapy and endometrial cancer cannot be overlooked. The longer estrogen
replacement therapy was used, the higher the risk in endometrial cancer for
perimenopausal and postmenopausal women. The odds ratio for users of 1.0-2.5 years,
2.6-5.0 years, 5.1-7.5 years, and 7.6-10.0 years were 1.0, 2.9, 4.3, and 8.2 times the risk
compared to those who never used estrogen replacement therapy, respectively (Kelsey et
al., 1982).
Relative to women who had never used hormones, women who had taken
unopposed estrogen had a 4.0 fold increase (95% Cl 3.1-5.1) in risk for endometrial
cancer (Beresford et al., 1997). Another study found that the risk of endometrial cancer
among women who had used unopposed estrogen for more than three years was over 5.0
times that of women who never used hormones (RR=5.7, 95% Cl 2.5-12.8). In contrast,
women using progestagen for at least six months of their estrogen replacement regimen,
had an RR of only 1.6 (95% Cl 0.6-3.9). These results provide evidence that the use of
progestagen during hormone therapy can reduce the excess risk of endometrial cancer
associated with long-term postmenopausal estrogen use (Voigt et al., 1991). Estrogen use
was associated with a significant threefold elevation in risk for endometrial cancer
(RR=3.0, 95% Cl 1.7-5.1) in a case-control study from seven hospitals in five US cities
(Brinton & Hoover, 1993).
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Post-menopausal bleeding is a physiological response to atypical hyperplasia of the
endometrial lining. Postmenopuasal estrogen taken alone commonly causes proliferation of
the uterine lining. Progestational agents are known suppressors of endometrial cell growth,
which may offset proliferation of the lining when incorporating progesterone into hormone
therapy. The presence of a progestogen, regardless of whether it is an endogenous or an
exogenous source, is associated with a relatively low incidence of endometrial cancer
(Voigt et al., 1994). By the addition of a progestin element, post-menopausal therapy can
remain low risk. A study by Gambrell (1984) showed that estrogen-progestogen users have
both significantly lower incidence of endometrial cancer than unopposed estrogen users
(Relative risk at 0.2 with p<-.0001) and untreated women (Relative risk at 0.3 with
p<=.005). Overall, the endometrial lining is extremely sensitive to exogenous hormones.
A much greater risk in developing endometrial cancer is evident when estrogen is used
alone or when the estrogenic component is emphasized in estrogen-progesterone
combination preparations (Weiss & Sayvetz, 1980).
Post-menopausal use in the United States
Post-menopausal estrogen has been a popular and frequently prescribed therapy in
the United States during the past three decades. An exponential increase in use began in
the 1940s and 1950s, initiated by experimental studies and clinical estrogen replacement
therapy for postmenopausal women. Use of exogenous estrogen has been advocated for
preventing osteoporosis, cardiovascular disease, hot flashes, vaginal dryness, and other
symptoms of estrogen deprivation at the peri- and postmenopausal time period. In the
late 1960s and 1970s, estrogen use gained popularity because of the widely held belief by
29
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TABLE 6
Summary of prevalence of postmenopausal estrogen use in the US and
Asia
Study Overall Prevalence Prevalence
among women
with surgically
induced
menopause
Prevalence
among
women with
natural
menopause
US Cauley (1990)
Harris (1990)
13.7%
32%
Johannes(1994) 12.3% 45.0% 9.3%
W olf (1991) 21% 38.4% 15.5%
Asains
dwelling in US
Davis (1995) 15% for 1980s
25-30% for 1990s
Asia Lee (1995)
Singapore
Nagata (1996)
Japan
1.8%
2.5%
(current users in
1992)
6.3%
(previously used)
of hormone use was 12.3 percent during the study. Again, a higher prevalence of
hormone use was found in women with surgical menopause (45 percent) compared to
those who went through natural menopause (9.3 percent) (Johannes et al., 1994).
Another community survey in California, 1986-1987, found that of 32 percent of 954
postmenopausal women reported current hormone use (26 percent took estrogen alone
and 6 percent took estrogen and progestin in combination) (Harris et al., 1990). In a
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1986-1988 multicenter prospective study of osteoporotic fractures conducted by Cauley
and associates (1990), 13.7 percent of 9,704 women who were non-black and 65 years
and older reported current use of oral estrogen replacement therapy (10.9 percent taking
estrogen alone and 3.8 percent taking an estrogen-progestin combination).
Post-menopausal use in the Asia
In contrast to women from western countries, who tend to be well educated about
the implications of the menopause, a lack of awareness in Asian countries may result in
few women choosing postmenopausal hormones to protect against long-term
complications. In fact, Haines and associates (1995) found that only 8 percent of women
from Hong Kong and 4 percent from southern China knew that hormone replacement
therapy could be used to treat postmenopausal women (Haines et al., 1995). The majority
of women in the United Kingdom, 89.6 percent of 539 perimenopausal women surveyed,
had heard of treatment for menopause, including hormone replacement (Haines et al.,
1995).
This large discrepancy in knowledge translates to potentially large differences in
hormone use, when comparing Western to Asian countries. Very few women in Hong
Kong are using Hormone Replacement Therapy (HRT) (Haines et al., 1995). Unofficial
Hong Kong figures suggest that a maximum of 6 percent of the women aged 50-65 are
current users. Although no figures are available to estimate the number of
postmenopausal women using HRT in mainland China, it appears to be lower than that in
Hong Kong, and may be well below 1 percent (Haines et al., 1995). A Singapore study
of subjects with post-menopausal bleeding (a symptom of endometrial cancer) reported that
31
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less than 1.8 percent of its subjects had used estrogen replacement therapy (Lee et al.,
1995).
In yet another Asian country, Japan, it is also quite rare for women to receive long
term estrogen drugs near their climacterium (Noda et al., 1987). A community-based study
in 1992 examined the prevalence of hormone replacement therapy in the Gifu Prefecture
of Japan (Nagata et al., 1996). From a total of 8,791 females aged 45-64 years old, only
2.5 percent of the women reported current use of HRT, and 5.2 percent reported previous
use of HRT (Nagata et al., 1996). In a population-based study in Shanghai, the
investigators noted that exogenous hormones were rarely used in this population (Shu et
al., 1993). In a survey of 500 Filipino women aged 40-50 years, residing mostly in
Metropolitan Manila, only 31 percent consulted a physician for menopause-related
ailments. Of the individuals who chose consultation, 86 percent were prescribed
medication, and only 52 percent of those complied with and followed the prescription.
The most commonly prescribed medications were tranquilizers (41 percent) rather than
hormones (19 percent) (Ramoso-Jalbuena, 1994). Among those who can afford
hormonal replacement therapy (HRT), the fear of cancer was the greatest impediment to
the acceptance of HRT. The questions most frequently asked by Filipinos were: “Does
estrogen cause cancer?” and “Are hormones dangerous?” The majority of Filipino
women are still influenced by the uterine cancer scare of the mid-1970s (Ramoso-
Jalbuena, 1994).
32
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Post-menopausal use in the Asian dwelling in the US
Patterns of estrogen use among Asian-Americans are quite different from their
native counterparts. In a longitudinal study of estrogen and calcium use among a cohort
of Japanese-American women living in Hawaii, women using exogenous postmenopausal
estrogen were younger and had more often used contraceptive estrogen in the past. The
proportion of estrogen users has increased over the past decade. Fifteen percent of the
women used estrogen in the early 1980s; by the 1990s, use had increased to 25-30
percent. Women under age 65 were twice as likely to initiate estrogen use and less likely
to quit estrogen use, than older women (Davis et al., 1995).
Overall findims
The findings for our study showed that endometrial cancer rates in Asian migrants
to the US were less than those for US-born Asians, which were even less than those for
US Whites. The trend in endometrial cancer rate is consistent with the global pattern of
estrogen replacement therapy use. In fact, acute menopausal symptoms occur less
frequently in Asian than in Caucasian women (Chung et a l, 1996). A randomized,
double-blind, placebo-controlled, crossover study in Hong Kong demonstrated no
effectiveness of estrogen replacement therapy when compared with placebo group in
Chinese women (Chung et al., 1996). Hormone therapy has had greater acceptance and
use in Western countries because of its ability to benefit cardiovascular health and to
alleviate menopausal symptoms. These positive attributes maybe outweighed by the
increased risk for endometrial cancer. The endometrial cancer risks can be moderated
33
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when a progesterone agent is administered concurrently with estrogen therapy in
postmenopausal women (Creasy et al, 1992). Addition of progesterone reduces the
incidence of endometrial hyperplasia through suppression of endometrial cells
proliferation. Combined progesterone and estrogen therapy is associated with a relatively
low risk of endometrial cancer (Brinton & Hoover, 1993; Voigt et a l, 1991).
Endometrial cancer is a more prominent health problem in Western and developed
countries. The United States and Canada are areas of highest risk. The rates among US
Whites are greater than rates among European women (Muir et a l, 1987). Interestingly,
the incidence among Asian women living in the United States is considerably higher than
their counterparts in living in Asia. Our study further supports the role of environmental
or modifiable exposures in endometrial cancer etiology. The Chinese, Japanese, and
Filipino women who migrate to the US have an increased endometrial cancer risk and,
after several generations in the US, their descendents have rates that approach US white
women. Dietary change, obesity, and postmenopausal estrogen usage are plausible
reasons for this increasing risk of endometrial cancer in Asian migrants and their
descendants.
Our study shows an increasing incidence of endometrial cancer in US-born and
migrant Asians, which moves towards the higher rate found in US whites. We believe
this trend can be attributed to increasing BMI and the use of estrogen replacement therapy
in US Asians when compared to Asians living in their homeland. The strength of our
findings arises from the use of incidence data. Previous migrant studies using mortality
rates would not accurately measure the occurrence of endometrial cancer because this
34
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disease is not extremely fatal. Endometrial cancer was among the five most frequently
diagnosed cancers in these three ethnic groups but was not among the five most common
cancer deaths for these women (Table 7). In the US SEER data for 1988-1992, incidence
and mortality rates for endometrial cancer are summarized in Table 8.
TABLE 7
Most common cancers in US women (Rates are “average annual” per
100,000 population, age-adjusted to 1970 U.S. standard)
Race Five Most Frequently Five Most Common Types of
_____________Diagnosed Cancers__________ Cancer Deaths_____________
Chinese Breast 55.0 Lung and Bronchus 18.5
Colon and Rectum 33.6 Breast 11.2
Lung and Bronchus 25.3 Colon and Rectum 10.5
Corpus Uteri 11.6 Pancreas 5.1
Ovary 9.3 Stomach 4.8
Japanese Breast 82.3 Lung and Bronchus 12.9
Colon and Rectum 39.5 Breast 12.5
Stomach 15.3 Colon and Rectum 12.3
Lung and Bronchus 15.2 Stomach 9.3
Corpus Uteri 14.5 Pancreas 7.0
Filipino Breast 73.1 Breast 11.9
Colon and Rectum 20.9 Lung and Bronchus 10.0
Lung and Bronchus 17.5 Colon and Rectum 5.8
Thyroid 14.6 Pancreas 3.5
Corpus Uteri 12.1 Ovary 3.4
35
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TABLE 8
SEER Incidence and Mortality Rates, 1988-1992 (Rates are “average
annual” per 100,000 population, age-adjusted to 1970 U.S. standard)
Race SEER Incidence Mortality Rates
Whites 22.3 3.2
Chinese 11.6 2.2
Japanese 14.5 1.9
Filipino 12.1 1.3
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
BIBLIOGRAPHY
(1997). Update: prevalence of overweight among children, adolescents, and adults—
United States, 1988-1994. MMWR Morb Mortal Wkly Rep, 46(9), 198-202.
Akan, G.E., & Grilo, C.M. (1995). Sociocultural Influences on Eating Attitudes and
Behaviors, Body Image, and Psychological Functioning: A Comparison of
African-American, Asian-American, and Caucasian College Women.
International Journal o f Eating Disorders, 18(2), 181 -187.
Ballard-Barbash, R., & Swanson, C.A. (1996). Body weight: estimation of risk for breast
and endometrial cancers. Am JClin Nutr, 63(3 Suppl), 437s-41s.
Beresford, S.A., Weiss, N.S., Voigt, L.F., & McKnight, B. (1997). Risk of endometrial
cancer in relation to use of oestrogen combined with cyclic progestagen therapy in
postmenopausal women. Lancet, 349(9050), 458-61.
Brinton, L.A., Berman, M.L., Mortel, R., Twiggs, L.B., Barrett, R.J., Wilbanks, G.D.,
Lannom, L., & Hoover, R.N. (1992). Reproductive, menstrual, and medical risk
factors for endometrial cancer: results from a case-control study. American
Journal o f Obstetrics & Gynecology, 167(5), 1317-25.
Brinton, L.A., & Hoover, R.N. (1993). Estrogen replacement therapy and endometrial
cancer risk: unresolved issues. The Endometrial Cancer Collaborative Group.
Obstet Gynecol, 81(2), 265-71.
Carr, B.R. (1996). HRT management: the American experience. Eur J Obstet Gynecol
ReprodBiol, 64 Suppl, S17-20.
Cauley, J.A., Cummings, S.R., Black, D.M., Mascioli, S.R., & Seeley, D.G. (1990).
Prevalence and determinants of estrogen replacement therapy in elderly women.
American Journal o f Obstetrics and Gynecology, 163(5), 1438-1444.
Chung, T.K., Yip, S.K., Lam, P., Chang, A.M., & Haines, C.J. (1996). A randomized,
double-blind, placebo-controlled, crossover study on the effect of oral oestradiol
on acute menopausal symptoms. Maturitas, 25(2), 115-23.
Creasy, G.W., Kafrissen, M.E., & Upmalis, D. (1992). Review of the endometrial effects
of estrogens and progestins. Obstet Gynecol Surv, 47(9), 654-78.
37
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Davis, J.W., Ross, P.D., Johnson, N.E., & Wasnich, R.D. (1995). Estrogen and calcium
supplement use among Japanese-American women: effects upon bone loss when
used singly and in combination. Bone, 77(4), 369-73.
Elwood, J.M., Cole, P., Rothman, K.J., & Kaplan, S.D. (1977). Epidemiology of
endometrial cancer. Journal o f the National Cancer Institute, 59(4), 1055-60.
Eriksen, E.F., Kassem, M., & Langdahl, B. (1996). European and North American
Experience with HRT for the prevention of osteoporosis. Bone, 19(5 Suppl),
179s-183s.
Franks, A.L., Kendrick, J.S., & Tyler, C.W., Jr. (1987). Postmenopausal smoking,
estrogen replacement therapy, and the risk of endometrial cancer. American
Journal o f Obstetrics & Gynecology, 156(1), 20-3.
Fujimoto, W.Y., Bergstrom, R.W., Boyko, E.J., Leonetti, D.L., Newell Morris, L.L., &
Wahl, P.W. (1995). Susceptibility to development of central adiposity among
populations. Obes Res, 3 Suppl 2, 179s-186s.
Gambrell, R.D., Jr. (1984). Hormones in the etiology and prevention of breast and
endometrial cancer. South Med J, 77(12), 1509-15.
Grady, D., & Emster, V.L. (1996). Endometrial Cancer. In D. Schottenfeld & J. Fraumeni
(Eds.), Cancer Epidemiology and Prevention (Second ed., pp. 1058-1089). New
York: Oxford University Press, Inc.
Haines, C.J., Rong, L., Chung, T.K., & Leung, D.H. (1995). The perception of the
menopause and the climacteric among women in Hong Kong and southern China.
Preventive Medicine, 24(3), 245-8.
Harris, R.B., Laws, A., Reddy, V.M., King, A., & Haskell, W.L. (1990). Are Women
Using Postmenopausal Estrogens? A Community Survey. American Journal o f
Public Health, 50(10), 1266-1268.
Henderson, B.E., Casagrande, J.T., Pike, M.C., Mack, T., Rosario, I., & Duke, A. (1983).
The epidemiology of endometrial cancer in young women. British Journal o f
Cancer, 47(6), 749-56.
Hill, H.A., & Austin, H. (1996). Nutrition and endometrial cancer. Cancer Causes
Control, 7(1), 19-32.
Hoogerland, D.L., Buchler, D.A., Crowley, J.J., & Carr, W.F. (1978). Estrogen use - risk
of endometrial carcinoma. Gynecologic Oncology, 6(5), 451-8.
38
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Huang, C., Ross, P.D., Fujiwara, J., Davis, J.W., Epstein, R.S., Kodama, K., & Wasnich,
R.D. (1996). Determinants of Vertebral Fracture Prevalence Among Native
Japanese Women and Women of Japanese Descent Living in Hawaii. Bone, 18(5),
437-442.
Hulka, B.S., Fowler, W.C., Jr., Kaufman, D.G., Grimson, R.C., Greenberg, B.G., Hogue,
C.J., Berger, G.S., & Pulliam, C.C. (1980). Estrogen and endometrial cancer:
cases and two control groups from North Carolina. American Journal o f
Obstetrics & Gynecology, 137(1), 92-101.
Jensen, J., Christiansen, C., & Rodbro, P. (1985). Cigarette smoking, serum estrogens,
and bone loss during hormone-replacement therapy early after menopause. New
England Journal o f Medicine, 313(16), 973-5.
Johannes, C.B., Crawford, S.L., Posner, J.G., & McKinlay, S.M. (1994). Longitudinal
Patterns and Correlates of Hormone Replacement Therapy Use in Middle-aged
Women. American Journal o f Epidemiology, 140(5), 439-452.
Kelsey, J.L., LiVolsi, V.A., Holford, T.R., Fischer, D.B., Mostow, E.D., Schwartz, P.E.,
T, O.C., & White, C. (1982). A case-control study of cancer of the endometrium.
Am J Epidemiol, 116(2), 333-42.
Kin, K., Lee, J.H., Kushida, K., Sartoris, D.J., Ohmura, A., Clopton, P.L., & Inoue, T.
(1993). Bone density and body composition on the Pacific rim: a comparison
between Japan-bom and U.S.-bom Japanese-American women, J Bone Miner
Res, 8(1), 861-9.
Koss, L.G., Schreiber, K., Oberlander, S.G., Moukhtar, M., Levine, H.S., & Moussouris,
H.F. (1981). Screening of asymptomatic women for endometrial cancer. CA
Cancer J Clin, 31(5), 300-17.
Kuczmarski, R.J., Flegal, K.M., Campbell, S.M., & Johnson, C.L. (1994). Increasing
prevalence of overweight among US adults. The National Health and Nutrition
Examination Surveys, 1960 to 1991 [see comments]. Jama, 272(3), 205-11.
La Vecchia, C., Decarli, A., Fasoli, M., & Gentile, A. (1986). Nutrition and diet in the
etiology of endometrial cancer. Cancer, 57(6), 1248-53.
La Vecchia, C., Franceschi, S., Decarli, A., Gallus, G., & Tognoni, G. (1984). Risk
factors for endometrial cancer at different ages. Journal o f the National Cancer
Institute, 75(3), 667-71.
39
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Lee, M.M., Wu Williams, A., Whittemore, A.S., Zheng, S., Gallagher, R., Teh, C.Z.,
Zhou, L., Wang, X., Chen, K., Ling, C., & et al. (1994). Comparison of dietary
habits, physical activity and body size among Chinese in North America and
China. Int J Epidemiol, 23(5), 984-90.
Lee, W.H., Tan, K.H., & Lee, Y.W. (1995). The aetiology of postmenopausal bleeding— a
study of 163 consecutive cases in Singapore. Singapore Med J, 36(2), 164-8.
Lesko, S.M., Rosenberg, L., Kaufman, D.W., Helmrich, S.P., Miller, D.R., Strom, B.,
Schottenfeld, D., Rosenshein, N.B., Knapp, R.C., Lewis, J., & et al. (1985).
Cigarette smoking and the risk of endometrial cancer. New England Journal o f
Medicine, 575(10), 593-6.
Lesko, S.M., Rosenberg, L., Kaufman, D.W., Stolley, P., Warshauer, M.E., Lewis, J.L.,
Jr., & Shapiro, S. (1991). Endometrial cancer and age at last delivery: evidence for
an association [see comments], American Journal o f Epidemiology, 755(6), 554-9.
Levi, F., La Vecchia, C., Negri, E., Parazzini, F., & Franceschi, S. (1992). Body mass at
different ages and subsequent endometrial cancer risk. Int J Cancer, 50(4), 567-
71.
Lumbiganon, P. (1994). Depot-medroxyprogesterone acetate (DMPA) and cancer of the
endometrium and ovary. Contraception, 49(3), 203-9.
Mack, T.M., Pike, M.C., Henderson, B.E., Pfeffer, R.I., Gerkins, V.R., Arthur, M., &
Brown, S.E. (1976). Estrogens and endometrial cancer in a retirement community.
New England Journal o f Medicine, 294(23), 1262-7.
Michnovicz, J.J., Hershcopf, R.J., Naganuma, H., Bradlow, H.L., & Fishman, J. (1986).
Increased 2-hydroxylation of estradiol as a possible mechanism for the anti
estrogenic effect of cigarette smoking. New England Journal o f Medicine,
575(21), 1305-9.
Muir, C., Waterhouse, J., Mack, T., Powell, J., & Whelan, S. (Eds.). (1987). Cancer
Incidence in Five Continents, Volume V (IARC Sci. Pub. No.88 ed.). (Vol. 5).
Lyon, France: International Agency for Research on Cancer.
Nagata, C., Matsushita, Y., & Shimizu, H. (1996). Prevalence of hormone replacement
therapy and user's characteristics: a community survey in Japan. Maturitas, 25(3),
201-7.
40
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Noda, K., Yanagawa, H., Kurihara, S., Sugimoto, O., Takamizawa, H., Tenjin, Y.,
Okudaira, Y., Suzuki, T., Morizuka, T., Moriwaki, S., & et al. (1987). High risk
factors for cancer of the endometrium among Japanese women. Asia Oceania J
Obstet Gynaecol, 13(4), 369-77.
Parazzini, F., La Vecchia, C., Bocciolone, L., & Franceschi, S. (1991). The epidemiology
of endometrial cancer. Gynecol Oncol, 41(\), 1-16.
Parkin, D.M., Muir, C.S., Whelan, S.L., Gao, Y.T., Ferlay, J., & Powell, J. (Eds.). (1992).
Cancer Incidence in Five Continents, Volume VI (IARC Sci. Pub. No. 120 ed.).
(Vol. 6). Lyon, France: International Agency for Research on Cancer.
Popkin, B.M., Paeratakul, S., Ge, K., & Fengying, Z. (1995). Body Weight Patterns
among the Chinese: Results from the 1989 and 1991 China Health and Nutrition
Surveys. American Journal o f Public Health, 85(5), 690-694.
Ramoso-Jalbuena, J. (1994). Climacteric Filipino women: a preliminary survey in the
Philippines. Maturitas, 19(3), 183-90.
Shapiro, S., Kaufman, D.W., Slone, D., Rosenberg, L., Miettinen, O.S., Stolley, P.D.,
Rosenshein, N.B., Watring, W.G., Leavitt, T., Jr., & Knapp, R.C. (1980). Recent
and past use of conjugated estrogens in relation to adenocarcinoma of the
endometrium. New England Journal o f Medicine, 303(9), 485-9.
Shu, X.O., Zheng, W., Potischman, N., Brinton, L.A., Hatch, M.C., Gao, Y.T., &
Fraumeni, J.F., Jr. (1993). A population-based case-control study of dietary
factors and endometrial cancer in Shanghai, People's Republic of China. Am J
Epidemiol, 137(2), 155-65.
Smith, D.C., Prentice, R., Thompson, D.J., & Herrmann, W.L. (1975). Association of
exogenous estrogen and endometrial carcinoma. New England Journal o f
Medicine, 293(23), 1164-7.
Spengler, R.F., Clarke, E.A., Woolever, C.A., Newman, A.M., & Osborn, R.W. (1981).
Exogenous estrogens and endometrial cancer: a case-control study and assessment
of potential biases. American Journal o f Epidemiology, 114(4), 497-506.
Stavraky, K.M., Collins, J.A., Donner, A., & Wells, G.A. (1981). A comparison of
estrogen use by women with endometrial cancer, gynecologic disorders, and other
illnesses. American Journal o f Obstetrics & Gynecology, 141(5), 547-55.
Stockwell, H.G., & Lyman, G.H. (1987). Cigarette smoking and the risk of female
reproductive cancer. American Journal o f Obstetrics & Gynecology, 157(1), 35-
40.
41
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Swanson, C.A., Potischman, N., Wilbanks, G.D., Twiggs, L.B., Mortel, R., Berman,
M.L., Barrett, R.J., Baumgartner, R.N., & Brinton, L.A. (1993). Relation of
endometrial cancer risk to past and contemporary body size and body fat
distribution. Cancer Epidemiol Biomarkers Prev, 2(4), 321-7.
Thomas, D.B., & Karagas, M.R. (1996). Migrant Studies. In D. Schottenfeld & J.
Fraumeni (Eds.), Cancer Epidemiology and Prevention (Second ed., pp. 236-254).
New York: Oxford University Press, Inc.
Voigt, L.F., Deng, Q., & Weiss, N.S. (1994). Recency, duration, and progestin content of
oral contraceptives in relation to the incidence of endometrial cancer
(Washington, USA). Cancer Causes Control, 5(3), 227-33.
Voigt, L.F., & Weiss, N.S. (1989). Epidemiology of endometrial cancer. In S. E.A. & D.
S. Alberts (Eds.), Endometrial Cancer (Vol. 49, pp. 1-21). Boston: Kluwer
Academic Publishers.
Voigt, L.F., Weiss, N.S., Chu, J., Daling, J.R., McKnight, B., & van Belle, G. (1991).
Progestagen supplementation of exogenous oestrogens and risk of endometrial
cancer. Lancet, 355(8762), 274-7.
Wang, J., Thornton, J.C., Burastero, S., Shen, J., Tanenbaum, S., Heymsfield, S.B., &
Pierson, R.N., Jr. (1996). Comparisons for body mass index and body fat percent
among Puerto Ricans, blacks, whites and Asians living in the New York City area.
Obes Res, 4(4), 377-84.
Weiss, N.S., Farewall, V.T., Szekely, D.R., English, D.R., & Kiviat, N. (1980).
Oestrogens and endometrial cancer: effect of other risk factors on the association.
Maturitas, 2(3), 185-90.
Weiss, N.S., & Sayvetz, T.A. (1980). Incidence of endometrial cancer in relation to the
use of oral contraceptives. N Engl J Med, 362(10), 551-4.
Weiss, N.S., Szekely, D.R., English, D.R., & Schweid, A.I. (1979). Endometrial cancer in
relation to patterns of menopausal estrogen use. Jama, 242(3), 261-4.
Wolf, P.H., Madans, J.H., Finucane, F.F., Higgins, M., & Kleinman, J.C. (1991).
Reduction of cardiovascular disease-related mortality among postmenopausal
women who use hormones: evidence from a national cohort. American Journal o f
Obstetrics & Gynecology, 164(2), 489-94.
Wynder, E.L., Escher, G.C., & Mantel, N. (1966). An epidemiological investigation of
cancer of the endometrium. Cancer, 19(4), 489-520.
42
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Ziel, H.K., & Finkle, W.D. (1975). Increased risk of endometrial carcinoma among users
of conjugated estrogens. New England Journal o f Medicine, 293(23), 1167-70.
43
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.

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Asset Metadata

Creator Liao, C. Katherine (author)

Core Title Endometrial cancer in Asian migrants to the United States and their descendants

School Graduate School

Degree Master of Science

Degree Program Applied biometry and epidemiology

Publication Date 12/09/2020

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag OAI-PMH Harvest

Language English

Contributor Digitized by ProQuest (provenance)

Advisor Ar[…], Goshe (committee chair), Mack, Wendy (committee member), Peters, Ruth K. (committee member)

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c89-412445

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Rights Liao, C. Katherine

Type texts

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