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Polymorphism of CYP2E1 gene and the risk of lung cancer among African-Americans and Caucasians in Los Angeles County
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Polymorphism of CYP2E1 gene and the risk of lung cancer among African-Americans and Caucasians in Los Angeles County
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Content
Polymorphism of CYP2E1 Gene and the Risk of Lung Cancer
among African-Americans and Caucasians
in Los Angeles County
by
Li Ding
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
(Epidemiology)
May, 1995
Copyright 1995 Li Ding
UNIVERSITY O F SO U TH ERN CALIFORNIA
THE GRADUATE SCHOOL
UNIVERSITY PARK
LOS ANGELES, CALIFORNIA 9 0 0 0 7
This thesis, written by
under the direction of hSLCl....Thesis Committee,
and approved by all its members, has been pre
sented to and accepted by the D ean of The
Graduate School, in partial fulfillment of the
requirements for the degree of
L ,l D / / 06r
/IgLi
Dean
D a te .....
Table of Contents
Introduction 1
Subjects and Methods 2
Identification of Cases and Controls 2
Statistical Methods 4
Laboratory Methods 5
Results 6
Discussion 1 1
Bibliography 14
Appendixes 15
ii
List of Tables
Table 1. Characteristics of the study population in cases and controls. 6
Table 2. Distribution of race, gender, smoking status and age by CYP2E1
genotype among control subjects. 7
Table 3. Distribution of race, gender, smoking status and age by CYP2E1
genotype among cases subjects. 8
Table 4. Distribution of cell type by CYP2E1 genotypes in the cases. 9
Table 5. Association between CYP2E1 and lung cancer risk in African-
Americans and Caucasians in Los Angeles County. Effect
of adjustment for age, race, gender, and smoking habits. 9
Table 6. Association between CYP2E1 and lung cancer risk in African-
Americans and Caucasians in Los Angeles County stratified
by race, gender, and smoking habits. 10
Appendix 1. Studies of the CYP2E1 polymorphism and lung cancer risk. 15
Appendix 2. Studies of the CYP2E1 gene and smoking habits. 16
iii
Introduction
Cytochromes P450 enzymes are involved in metabolic activation of many
nitrosamines including those in tobacco smoke. CYP2E1 is the most active P450 species
known in the metabolism of N-nitrosoethylmethylamine, N-nitrosopyrrolidine, benzene,
styrene, carbon tetrachloride, and trichloroethylene (Yang, 1985). Also, a higher
microsomal CYP2E1 N-nitrosodimethylamine (NDMA) demethylase activity is present in
normal tissues compared to tumors and was accompanied by corresponding change in
CYP2E1 protein concentration (Botto, 1994). Therefore, differences in the genotypes of
CYP2E1 may be responsible for interindividual variations in susceptibility to cancers
caused by these chemicals.
Several studies have investigated the possible association between the CYP2E1
polymorphism and lung cancer risk. The Dral restriction fragment length polymorphism
(RFLP) patterns o f CYP2E1 gene have been associated with a predisposition to lung
cancer in a Japanese population (Uematsu, 1991 & 1994). In contrast, some other studies
showed no association between Dral polymorphism and an increased risk of lung cancer in
the Finnish population ( Hirvonen, 1993), the Swedish population (Persson, 1993), or
United States Caucasian and African-Americans (Kato, 1992 & 1994). CYP2E1 Rsal
polymorphism was not associated with lung cancer susceptibility in studies in American
population (Kato, 1992), in Brazilians (Hamada, 1995) and in Finnish population
(Hirvonen, 1993). However, the Rsal polymorphism is more likely to direct affect the
gene expression than Dral polymorphism because it is located in the transcription
regulation region of the CYP2E1 gene (Hamada, 1995 & Stephens, 1994).
l
In this paper, we will examine the association between lung cancer risk and genetic
polymorphisms of RFLP of the CYP2E1 gene detected by the restriction enzyme Rsal in
the Los Angeles County population.
Subjects and Methods
Identification of cases and controls
Eligibility criteria for the study were as follows: resident in Los Angeles County,
aged 40-84, able to complete a questionnaire in English, Caucasian (non-Hispanic) or
African-American ethnicity, and no prior cancer other than nonmelanoma skin cancer. All
subjects were enrolled between 1991 and 1994.
Cases of lung cancer were identified from 35 hospitals in Los Angeles County. By
selecting these hospitals, we identified all cases of lung cancer seen at any of the hospitals
within 7 months of diagnosis. Enrollment was limited to newly diagnosed cases to avoid
bias that could result from the selective enrollment of cases who had survived for a long
period. Controls under age 65 were sampled from among licensed drivers and those over
65 from a random selection of Medicare beneficiaries provided by the Health Care
Financing Administration (HCFA). We frequency matched on age (within 10 year
intervals), sex and race to the distribution of these factors among cases diagnosed at our
network of catchment hospitals in the previous three years. We aimed to enroll twice as
many controls as cases.
We identified 1,119 potentially eligible cases. Of these 207 died before we could
obtain permission for patient contact from the physician and 260 of the 912 living cases
were ineligible. The physician declined permission for us to contact 36 of the 652 patients
not know to be ineligible. Among the remaining 616, we were unable to locate 92, 158
declined to participate and we ended the study before we could enroll 10 cases who
agreed to participate. Thus, we enrolled 356 eligible cases (31.8% of total potential
eligible cases).
We sent letters to 3,193 potential controls. Subjects were asked to write a phone
number on an enclosed postcard and return it. We sent a total of four letters if we received
no response. We looked up phone numbers of all nonrespondents and tried 12 times to
call each subject with a listed phone number. We then attempted to visit the addresses of
all subjects not reached after 12 tries as well as all unlisted subjects.
The address on the DMV or HCFA tape was incorrect for 752 subjects and we
were unable to obtain a usable address for these. We determined that 157 persons to
whom we sent letters were not eligible because they no longer lived in Los Angeles
County. Of the 2,284 subjects with valid addresses we obtained a response on 1,573.
Responses for these 1,573 indicated that 94 were ineligible, 71 were deceased, 351
declined to participate and 1,057 expressed willingness to participate. Among these 1,057
subjects, 46 could not be reached before the end of the study, 831 were eligible on the
screening and 180 were ineligible. We were unable to enroll 100 of the 831 eligible,
willing subjects before we terminated data collection. Because the DMV tape does not
contain race identifiers and because Caucasians are more numberous than African-
Americans in the county, we identified more than our target number of Caucasians.
However, we continued to solicit potential subjects in order to identify additional African-
3
Americans. We enrolled 731 eligible controls (22.9% of total potential controls): 473
(64.7%) Caucasians and 258 (35.3%) African-Americans.
Subjects provided a blood sample and completed an in-person interview on risk
factors for lung cancer. The median time from diagnosis to enrollment was 3.7 months and
the maximum was 10 months. Among the 356 eligible cases and 731 eligible controls
enrolled, we obtained a DNA sample adequate for CYP2E1 genotyping on 341 cases and
706 controls.
The protocol was reviewed and approved by the human subjects committee at the
University of Southern California. We obtained written informed consent from all subjects.
Statistical Methods
Odds ratios and their 95% confidence intervals (Cl) were calculated by
unconditional logistic regression using the Epilog Plus, version 3.0, software program
(Epicenter Software, Pasadena CA). Terms for the frequency matching factors were
included. In all models, we adjusted for age as a continuous variable. To evaluate possible
confounding by smoking, we considered four metrics for exposure: usual amount smoked,
maximum amount smoked, years smoked and pack-years determined from lifetime history
of changes in the amount smoked and duration smoked at each level. In addition, we
evaluated logarithmic, square root and quadratic transformations of the smoking variables.
In the interest of parsimony, we chose a single term for the square root of pack-years to
adjust for smoking because this provided the best fit to the data. We tested for significance
of the difference in the odds ratios for the CYP2E1 genotype according to strata of race,
sex or smoking, by fitting multivariate models separately within the two strata of interest
and comparing the difference in the coefficients for CYP2E1 genotype to a standard
normal distribution. All p values presented are two-sided.
Laboratory Methods
DNA was prepared either from buffy coats (isolated from 10 whole blood) or
directly from 10 ml whole blood. In either case, the blood was collected in an EDTA tube
and frozen in Los Angeles and stored at -80°C prior to shipment on dry ice to New castle
upon Tyne, United Kingdom for processing. The samples were thawed and a nuclear
fraction was prepared by lysis with 10 volumes 0.32 M sucrose, 10 mM Tris-HCl, pH 7.4,
5 mM MgCl2, 1% Triton X-100 and centrifugation at 1600 g for 5 min. The pellet was
resuspended in 2 ml phosphate buffered saline and DNA was extracted on an Applied
Biosystems model 340A nucleic acid extractor using the recommended protocol.
Genotyping for the functional upstream polymorphism detectable with Rsal and
involving a binding site for the transcription factor HNF1 (Hayashi, 1991) has been carried
out on 856 subjects. The primers were (i) TTCATTCTGTCTTCTAACTGG and (ii)
CCAGTCGAGTCTACATTGTCA. All PCR reactions were carried out in 0.5 ml
polypropylene tubes in a Techne PHC-1 programmable heating block in a final volume of
50 microlitres. The reaction buffer was 10 mM Tris-HCl, pH 8.8, 1.5 mM MgC12, 50
mM KC1, 0.1% (v/v) Triton X-100 with each primer at 0.25 microM, nucleotides at 0.25
microM, 3% dimethylsulphoxide and Tbr polymerase (1 unit/50 microlitre reaction) (NBL
Gene Sciences, Cramlington, Northumberland, UK). The PCR conditions were 35 cycles
of 1 min at 95°C, 2 min at 45°C and 2 min at 70°C. Twenty microlitre of each sample was
5
digested with 10 unites Rsal at 37°C for 3 h and the products were analyzed by
electrophoresis on a 4% Nusieve 3:1 agarose gel.
Results
Table 1 includes distributions of CYP2E1 genotype, age, race, gender, smoking
and histologic type of lung cancer. The age distributions of cases and controls were not
significantly different.
Table 1. Characteristics of the study population in cases and controls (n=1047)
Variable CASES
N Proportion
CONTROLS
N Proportion
Total Study Population 341 706
CYP2E1 Genotype
wild type 328 0.96 665 0.94
mutant 13 0.04 41 0.06
Race
African-American 157 0.46 247 0.35
Caucasian 184 0.54 459 0.65
Gender
Female 141 0.41 239 0.34
Male 200 0.59 467 0.66
Cell Type
adenocarcinoma 121 0.35
squamous 82 0.24
small cell 44 0.13
other 94 0.28
Smoking
Never 15 0.04 239 0.34
Past 237 0.70 329 0.46
Current 89 0.26 138 0.20
Age
40-49 27 0.08 45 0.06
50-59 81 0.24 198 0.28
60-64 68 0.20 177 0.25
65-69 72 0.21 133 0.19
70-79 79 0.23 142 0.20
804- 14 0.04 11 0.02
mean (sd) 62.6 (8.5) 63.6 (9.5)
6
In the control group, the frequency of the CYP2E1 mutant genotype did not differ
significantly according to gender, smoking status or age (Table 2).
Table 2. Distribution of race, gender, smoking status and age by CYP2E1 genotype among control
subjects.
Total CYP2E1
wild type
CYP2E1
mutant
Proportion
mutant
Total 706 665 41 0.06
Race*
African-American 247 242 5 0.02
Caucasian 459 423 36 0.08
Gender
Female 239 230 9 0.04
Male 467 435 32 0.07
Smoking status
African-American
Never 77 77 0 0.00
Past 101 98 3 0.03
Current 69 67 2 0.03
Caucasians
Never 162 152 10 0.06
Past 228 209 19 0.08
Current 69 62 7 0.10
Age
40-49 45 41 4 0.09
50-59 198 185 13 0.07
60-64 177 169 8 0.05
65-69 135 124 9 0.07
70-79 142 135 7 0.05
80+ 1 1 1 1 0 0.00
*: p-value < 0.05 between two ethnic groups.
However, the frequency of the CYP2E1 mutant genotype among African-American was
significantly lower than among Caucasians (0.02 versus 0.08, p<0.05). Also, the
distribution of smoking habits (never, past, current) are markedly different between
7
African-Americans and Caucasians (p<0.05). These differences did not exist in our cases
(Table 3).
Table 3. Distribution of race, gender, smoking status and age by CYP2E1 genotype among case
subjects.
Total CYP2E1
wild type
CYP2E1
mutant
Proportion
mutant
Total 341 328 13 0.04
Race
African-American 157 154 3 0.02
Caucasian 184 174 10 0.05
Gender
Female 141 137 4 0.05
Male 200 191 9 0.03
Smoking status
African-American
Never 8 8 0 0.00
Past 122 99 3 0.02
Current 47 47 0 0.00
Caucasians
Never 7 7 0 0.00
Past 135 129 6 0.04
Current 42 38 4 0.10
Age
40-49 27 26 1 0.04
50-59 81 77 4 0.05
60-64 68 64 4 0.06
65-69 72 70 2 0.03
70-79 79 77 2 0.03
80+ 14 14 0 0.00
Examing odds ratio for CYP2E1 mutant genotype and lung cancer risk by
histology - adenocarcinoma, small cell carcinoma, squamous cell carcinoma, and all other
types combined - the association was most marked for the adenocarcinoma and all other
types combined but numbers were too small to provide stable estimates (Table 4). The
odds ratio for squamous carcinoma was statistically significantly different from the odds
ratio for adenocarcinoma (p<0.05), but not from the other two cell types.
Table 4. Distribution of cell type by CYP2E1 genotypes in the cases.
Cell Type
Genotype
wild type mutant O R * (95% Cl)
Controls 665 41
Cases
adenocarcinoma 119 2 0.31 (0.07-1.36)
squamous 75 7 1.75 (0.72-4.28)
small cell 42 2 0.67 (0.14-3.11)
other 92 2 0.39 (0.09-1.75)
* Control group serves as the reference category in computing odds ratio and 95% confidence interval.
Odds ratios arc adjusted for age, race, sex, and smoking.
We evaluated possible confounding of the age-adjusted association by frequency
matching factors, such as race and sex as well as smoking (Table 5).
Table 5. Association between CYP2E1 and lung cancer risk in African-Americans and
Caucasians in Los Angeles County. Effect of adjustment for age, race, gender, and smoking habits.
Adjustment CYP2E1 wild type CYP2E1 mutant
Factors OR* 95 % Cl
Age 1.00 0.66 0.35-1.25
Race 1.00 0.72 0.38-1.37
Gender 1.00 0.67 0.35-1.27
Smoking+ 1.00 0.58 0.30-1.14
Age, Race 4 1.00 0.74 0.39-1.40
Age, Gender 1.00 0.69 0.36-1.30
Age, Smoking 1.00 0.58 0.30-1.14
Age, Race, Gender 1.00 0.77 0.40-1.47
Age, Gender, Smoking 1.00 0.64 0.32-1.27
Age, Race, Smoking 1.00 0.68 0.34-1.35
Age, Race, Smoking , Gender 1.00 0.75 0.37-1.51
* CYP2E1 homozygous wild type serves as the reference category in computing odds ratio and 95% confidence
interval.
+ Smoking is modelled by the square root of pack-years.
The age-adjusted odds ratio for the CYP2E1 mutant type in relation to lung cancer risk
was 0.66 (95% Cl 0.35-1.25). Addition of race, gender and smoking to the model resulted
in a modest change in the odds ratio to 0.75 (95% Cl 0.37-1.51). Relatively, the biggest
change occurred when race was added to the model. For completeness, all analysis within
each strata of the frequency matching factors were adjusted for matching factors other
than that stratification factor and smoking.
We examined the association between CYP2E1 and lung cancer risk within strata
of gender, race and smoking habits (Table 6).
Table 6. Association between CYP2E1 and lung cancer risk in African-Americans and
Caucasians in Los Angeles County stratified by race, gender, and smoking habits.
Category CYP2E1 wild type
cases controls
CYP2E1
cases
mutant
controls
OR 95% Cl
All subjects 328 665 13 41 0.75 (0.37-1.51)
Race*
African-American 154 242 3 5 0.81 (0.17-3.95)
Caucasian 174 423 10 36 0.76 (0.35-1.66)
Gcndcr@
Female 137 230 4 9 0.80 (0.19-3.30)
Male 191 435 9 32 0.71 (0.33-1.52)
GST Genotype#
positive 197 376 5 21 0.62 (0.21-1.86)
null 130 289 8 20 0.94 (0.38-3.33)
Smoking Habits##
Non Smoker 15 229 0 10
Non Smoker & < 40 159 509 7 28 1.13 (0.47-2.69)
< 40 pack years** 144 280 7 18 1.09 (0.43-2.76)
>= 40 pack years 169 156 6 13 0.47 (0.17-1.27)
* Odds ratio for each racial group arc adjusted for age, gender, and smoking. Smoking in all models refers to a
continuous term for the square root of pack-years.
@ Odds ratios by gender arc adjusted for age, race, and smoking.
U Odds ratio by GST genotype are adjusted for age, race, gender, and smoking.
## Odds ratios by smoking habits are adjusted for age, race, and gender.
** Only smokers are dichotomized into pack-years groups; non-smokers are not included in less than 40 pack-years
group.
10
Although the prevalence of CYP2E1 mutant genotype differed markedly between African-
American and Caucasian in the control group, there was no support for a major
association between CYP2E1 genotype and lung cancer risk within either ethnic group.
Odds ratios in men and women were virtually identical. Those with a positive GST
genotype tend to have a lower odds ratio than those with a null GST genotype although
the difference may also due to chance. We also examined the association between
CYP2E1 and lung cancer risk separately in two categories of lifetime smoking history
divided at 40 pack-years, a cutpoint chosen for comparison to another study (Hamada et
al, 1995). Although the numbers are too small to provide stable estimates, having a
CYP2E1 mutant allele was associated with reduced risk of lung cancer (OR=0.47, 95% Cl
0.17-1.27) among smokers of 40 pack-years or more. However, the protective effect was
not found among lighter smokers (OR= 1.09, 95% Cl 0.43-2.76). The interaction between
CYP2E1 genotype and smoking was not significant.
Discussion
Several studies reported an interethnic difference for the Dral genetic
polymorphism of CYP2E1 between Asian and African-American, between Asian and
Caucasian (Stephens, 1994, Kato, 1992 & 1994). The rare allele frequencies for Japanese
were around 27%, 28% for Taiwanese, but only 2% for both African-American and
Caucasian. No difference has been found between African-American and Caucasian (Kato,
1992 & 1994). In this study, the proportion of subjects with Rsal rare allele in Caucasians
was markedly higher than that in African-Americans (0.08 vs 0.02, p<0.05).
Homozygotes for the CYP2E1 Dral c-alleles have been found to be associated
with a reduced risk for lung cancer in Japanese populations (Uematsu, 1991 & 1994). No
significant difference in the distribution of the CYP2E1 Dral c-allele between controls and
lung cancer patients were found in studies from Sweden, Finland and the United States.
The difference between the Japanese studies and those in other populations may reflect the
low frequency of mutant alleles in these other populations. Homozygotes mutants are rare
outside of the Japanese population.
In most of the studies, the analysis was done on Dral polymorphism rather than
Rsal polymorphism. Checking for a correlation between the Dral and Rsal
polymorphisms, the frequencies of the rare alleles at Rsal site and the Dral site are found
to be similar in a Japanese study (Hayashi, 1991) and among Taiwanese (Stephen, 1994).
But the presence of the major Dral allele did not consistently predict the presence of a
particular PstI allele in Caucasians (Hirvonen, 1993). Some argue that Dral polymorphism
which reflects a base pair change in intron 6 of the CYP2E1 gene is a region not likely to
direct affect gene expression whereas the Rsal polymorphism of CYP2E1 has a more
reasonable mechanistic basis than the Dral polymorphism because it is located in the
transcription regulation region of the CYP2E1 gene (Hamada, 1995 & Stephens, 1994).
Comparing with three other studies on CYP2E1 Rsal polymorphism, Kato et al.
reported an odds ratio of 0.90 (95% Cl 0.20-5.40); Hirvonen et al. had an odds ratio of
1.62 (95% Cl 0.35-7.39); after adjusting for age, sex, and race, Hamada et al. found an
odds ratio at 0.85 (95% Cl 0.36-2.02). The protection effect of Rsal rare allele in
12
CYP2E1 gene was most evident in our study although the association was weak and not
statistically significant.
The control response rate was low among our general population sample. Thus there is a
theoretical possibility of selection bias. However, we believe that it is very unlikely that
willingness to participate depends on CYP2E1 genotype. The fact that smoking behavior,
which is related to response rate in population surveys, is not related to CYP2E1
genotype, provides additional evidence against selection bias based on genotype.
This study is the largest one on CYP2E1 polymorphism and lung cancer risk.
However, given the low frequency of the Rsal mutant allele in both Caucasians and
African-Americans, the study was limited in its power to observe modest effects. It is
worth to note that although our sample size was much larger than the other studies, due to
the low incidence of heterozygotes and absence of homozygotes, the statistical power of
the study was limited. In the Rsal polymorphism, if we assumed an odds ratio of 0.7, the
power would be only 0.15; we needed 2,678 subjects in each of the case and control
group to achieve a power of 0.80. Given the low frequency of rare allele in CYP2E1
genotype, much larger studies would be needed to identify the association between lung
cancer risk and genetic polymorphisms of RFLP of the CYP2E1 gene.
13
Bibliography
Hamada GS, Sugimura H, Suzuki I, Nagura K, Kiyokawa E, Iwase T, Tanaka M,
Takahashi T, Watanabe S, Kino I, Tsugane S. The heme-binding region
polymorphism of cytochrome P4501A1, rather than the Rsal polymorphism of
IIE1 (CypIIEl), is associated with lung cancer in Rio de Janeiro. Cancer
Epidemiology, Biomarkers & Prevention 1995: 4, 63-67.
Hirvonen A, HusgafVel-Pursiainen K, Anttila S, Karjalainen A, Vainio H. The human
CYP2E1 gene and lung cancer: Dral and Rsal restriction fragment length
polymorphisms in a Finnish study population. Carcinogensis 1993: 4, 85-88.
Kato S, Shields PG, Caporaso NE, Hoover RN, Trump BF, Sugimura H, Weston A,
Harris CC. Cytochrome P450IIE1 genetic polymorphisms, racial variation, and
lung cancer risk. Cancer research 1992: 52, 6712-6715.
Kato S,Shields PG, Caporaso NE, Sugimura H, Trivers GE, Tucker MA, Trump BF,
Weston A, Harris CC. Analysis of cytochrome p450 2E1 genetic polymorphisms
in relation to human lung cancer. Cancer Epidemiology, Biomarkers & Prevention
1994: 3,515-18,
Persson I, Johansson I, Bergling H, Dahl ML, Seidegard J, Rylander R, Rannug A,
Hogberg J, Sundberg MI. Genetic polymorphism of cytochrome P4502E1 in a
Swedish population. FEBS Letters 1993: 319, 207-211.
Stephens EA, Taylor JA, Kaplan N, Yang CH, Hsieh LL, Lucier GW, Bell DA. Ethnic
variation in the CYP2E1 gene: polymorphism analysis of 695 African-Americans,
European-Americans and Taiwanese. Pharmacogenetics 1994: 4, 185-192.
Uematsu F, Kikuchi H, Motomiya M, Abe T, Sagami I, Ohmachi T, Wakui A, Kanamaru
R, Watanabe M. Association between restriction fragment length polymorphism of
the human cytochrome P450IIE1 gene and susceptibility to lung cancer. Japanese
Journal o f Cancer Research 1991: 82, 254-256.
Uematsu F, Ikawa S, Kikuchi H, Sagami I, Kanamaru R, Abe T, Satoh K, Motomiya M,
Watanabe M. Restriction fragment length polymorphism of the human CYP2E1
gene and susceptibility to lung cancer: possible relevance to low smoking
exposure. Pharmacogenetics 1994: 4, 58-63.
14
Appendix 1. Studies of the CYP2E1 polymorphism and lung cancer risk (Odds ratios are based on the comparison between the presence and absence of the rare allele).
First Author
Year
Ethnic G roup Cell Type Site OR (95% Cl) C ases Control
Proport. Rare Allele
C ase Control Source of Controls
Uematsu et al.
1991
Japanese all
squamous
small
large
adeno.
Dral 1.26(0.58-2.75)
1.43 (0.44-4.57)
1.23 (0.37-4.14)
1.43 (0.26-7.77)
1.08(0.33-3.49)
47
14
13
6
14
56 0.23
0.25
0.23
0.25
0.21
0.26
no history of cancer
Uematsu et al.
1994
Japanese all
squamous
small
large
adeno.
Dral 0.82(0.44-1.51)
0.76(0.31-1.90)
0.97 (0.38-2.59)
1.07(0.29-3.97)
1.19(0.55-2.59)
91 76 0.25
0.21
0.24
0.25
0.29
0.29 no history of cancer
Kato et al.
1992 Black
White
Black
White
all Rsal
Rsal
Rsal
Pstl
Pstl
Pstl
0.90 (0.20-5.40)
0.20 (0.02-2.43)
4.28 (0.35-50.6)
0.70 (0.20-5.40)
0.19(0.03-1.38)
4.13 (.034-48.8)
67 61 0.02 0.03
0.02 (for 87 Black)
0.02 (for 10 White)
0.27 (for 47 Jap.)
patients w/ chronic obstructive
pulmonary disease
patients w/ cancer at anatomicl
sites other than lung or urinary
bladder
Kato et al.
1994
Black,White all
squamous
adeno.
Black
White
Dral 1.93(0.66 - 5.65)#
1.15(0.34-3.91)
1.60(0.42 - 6.07)
1.24(0.25-6.14)
1.94(0.54-6.92)
58 56 0.10 0.08 patients w/ chronic obstructive
pulmonary disease
patients w/ cancer at anatomicl
sites other than lung or urinary
bladder
Hamada et al.
1995
Brazilian all Rsal 0.85 (0.36 - 2.02)* 113 108 0.05 0.06 patients w/ a variety of diagnoses
other than cancer, matched by age,
sex, race
Hirvonen et al.
1993
White all
squamous
adeno.
small cell
other
Dral 0.72 (0.36-1.45)
0.67(0.28-1.60)
0.36(0.10-1.27)
3.84 (0.90-16.40)
1.28(0.13-13.07)
101 121 0.02 0.012 healthy sample
Persson et al.
1993
White all Rsal
Dral
Taql
0.40(0.17-0.98)
0.87(0.51-1.52)
0.92(0.53-1.60)
195 152 0.09 0.10 healthy sample
#: Odds ratio is adjusted for age, sex, race, and smoking. *: Odds ratios are adjusted for age, sex, and race.
Appendix 2. Studies of CYP2E1 gene and smoking habits
CC+CD DD
First Author, Year Site Cutpoint Case Control Case Control OR * (95% C l)
Uematsu et al.
1994
Kato et al.
1994
Dral
Dral
<= 20 pack yrs
> 20 pack yrs
< 53 (median)
>53
17
22
5
5
8
32
24
47
23
24
2.27(0.89-5.81)
0.73 (0.37-1.45)
1.60(0.34-7.50)
1.40(0.35-5.71)
Hirvonen et al.
1993
Dral <= 25 pack yrs
26-50 pack yrs
> 50 pack yrs
ex-smoker
never-smoker
11
29
21
17
7
0.70(0.15-3.35)
0.93 (0.36-2.36)
0.55(0.15-1.99)
0.96 (0.32-3.39)
0
*: all controls served as the reference category regardless of their smoking habits.
#: odds ratios are adjusted for age, sex, and race.
16
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Asset Metadata
Creator
Ding, Li
(author)
Core Title
Polymorphism of CYP2E1 gene and the risk of lung cancer among African-Americans and Caucasians in Los Angeles County
School
Graduate School
Degree
Master of Science
Degree Program
Epidemiology
Degree Conferral Date
1995-05
Publisher
University of Southern California
(original),
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(digital)
Tag
biology, genetics,health sciences, public health,OAI-PMH Harvest
Format
masters theses
(aat)
Language
English
Contributor
Digitized by ProQuest
(provenance)
Advisor
Londen, Stephanie (
committee chair
), Azen, Stanley P. (
committee member
), Navidi, William (
committee member
)
Permanent Link (DOI)
https://doi.org/10.25549/usctheses-c18-8044
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1378410.pdf (filename),usctheses-c18-8044 (legacy record id)
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8044
Document Type
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Format
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Rights
Ding, Li
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The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the au...
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Repository Location
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Tags
biology, genetics
health sciences, public health