University of Southern California Dissertations and Theses

Association between body mass and benign prostatic hyperplasia in Hispanics: Role of steroid 5-alpha reductase type 2 (SRD5A2) gene

(USC Thesis Other)

Association between body mass and benign prostatic hyperplasia in Hispanics: Role of steroid 5-alpha reductase type 2 (SRD5A2) gene

PDF

Download a page range

Download transcript

Copy asset link

Request this asset

Transcript (if available)

Content ASSOCIATION BETWEEN BODY MASS AND BENIGN PROSTATIC
HYPERPLASIA IN HISPANICS: ROLE OF STEROID 5-ALPHA REDUCTASE
TYPE 2 (SRD5A2) GENE.
by
Md. Towhid Salam
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 BIOSTATISTICS/EPIDEMIOLOGY)
December 2003
Copyright 2003 Md. Towhid Salam
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
UMI Number: 1420397
INFORMATION TO USERS
The quality of this reproduction is dependent upon the quality of the copy
submitted. Broken or indistinct print, colored or poor quality illustrations and
photographs, print bleed-through, substandard margins, and improper
alignment can adversely affect reproduction.
In the unlikely event that the author did not send a complete manuscript
and there are missing pages, these will be noted. Also, if unauthorized
copyright material had to be removed, a note will indicate the deletion.
®
UMI
UMI Microform 1420397
Copyright 2004 by ProQuest Information and Learning Company.
All rights reserved. This microform edition is protected against
unauthorized copying under Title 17, United States Code.
ProQuest Information and Learning Company
300 North Zeeb Road
P.O. Box 1346
Ann Arbor, Ml 48106-1346
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
UNIVERSITY OF SOUTHERN CALIFORNIA
THE GRADUATE SCHOOL
UNIVERSITY PARK
LOS ANGELES, CALIFORNIA 90089-1695
This thesis, written by
t A C d * % U r A ld / S e d - f r m ,
under the direction o f k efs thesis committee, and
approved by all its members, has been presented to and
accepted b y the Director o f Graduate and Professional
Programs, in partial fulfillm ent o f the requirements fo r the
degree o f
D irector
Date D e c e m b e r 1 7 - 2 0 0 3
Thesis Compiittee
L - 7 C "
[ A ' chmr
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
ACKNOWLEDGEMENTS
I would like to express my utmost gratitude to Drs. Giske Ursin, Frank
Gilliland and Michael Goran for their guidance and support in preparing this
Master’s Thesis. I am also indebted to Drs. Juergen Reichardt and Eila Skinner for
their additional suggestions and comments in. the preparation of this manuscript.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
iii
TABLE OF CONTENTS
Acknowledgments.. ....... .....ii
List of Tables ....... .....iv
Abstract... ......................... .....................................................................................v
Introduction ...... ...1
Materials and Methods.................................. ..3
Study subjects ...... 3
Exposure assessment.............. ...4
Geno typing............ 4
Clinical data ..... .......5
Statistical Analysis............... ...5
Results........................... ...6
Discussion.. ............................................................................................................9
Bibliography ...... 13
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
iv
LIST OF TABLES
Table 1. Descriptive statistics of the study population (n=280).......................... 7
Table 2. Univariate odds ratios (ORs) and 95% confidence intervals (CIs) for any,
symptomatic and asymptomatic benign prostatic hyperplasia (BPH) associated with
body mass index (BMI) and other potential confounders......................... ..8
Table 3. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for any,
symptomatic and asymptomatic benign pro static hyperplasia (BPH) associated with
body mass index (BMI).. ....... .8
Table 4. Odds ratios (ORs) and 95% confidence intervals (CIs) for any, symptomatic
and asymptomatic benign prostatic hyperplasia (BPH) associated with body mass
index (BMI) stratified by V89L polymorphism in the steroid 5-a reductase type 2
(SRD5A2) gene .................................... 9
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
1
INTRODUCTION
Benign prostatic hyperplasia (BPH) is the most common prostatic disease
among elderly men (Guess 2001; Ziada and others 1999). Androgens are involved in
the development of BPH since the latter does not develop in men castrated before
puberty and is rare when castrations are done before age 40 (McConnell 1990). Age
is another known risk factor as both the incidence and prevalence of BPH increase
with age (Girman 1998; Guess 1992). With aging, serum testosterone (T) levels
decline and estrogen (E) levels increase (Levine and others 1997; Walsh 1988). The
resultant increase in the estrogen : androgen (E : T) ratio has been proposed to be
associated with BPH development (Gann and others 1995; Krieg and others 1993;
Shibata and others 2000). Since the peripheral aromatization of T to E that occurs in
adipose tissues results in an increased E : T ratio (Tchemof and Despres 2000),
several epidemiologic studies have examined the association between body mass
index (BMI), a measure of obesity, and BPH (Dahle and others 2002; Daniell 1993;
Fernandez and others 1992; Giovannucci and others 1994; Glynn and others 1985;
Lee and others 1997; Morrison 1992; Porta and others 1994; Seitter and Barrett-
Connor 1992; Signorello and others 1999). However, the data relating to BMI or
obesity and BPH are conflicting; some authors observed positive associations (Dahle
and others 2002; Giovannucci and others 1994; Lee and others 1997), others
observed inverse associations (Glynn and others 1985; Morrison 1992), whereas
others did not find any association between obesity and BPH (Fernandez and others
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
2
1992; Porta and others 1994; Seitter and Barrett-Connor 1992; Signorello and others
1999).
The development of BPH is dependent on androgens, and functional
polymorphism in androgen metabolism genes may modify BPH risk. The enzyme
steroid 5-a reductase type II (SRD5A2) is specific for prostate and it irreversibly
converts T to the more potent dihydrotestosterone (DHT) in the prostate (di Salle and
others 1998). A valine to leucine missense substitution at codon 89 (V89L) in exon 1
of the SRD5A2 gene has been shown to be associated with reduced SRD5A2
enzyme activity by more than 42% in an in-vitro study (Makridakis and others
2000), and 10-39% in humans (Allen and others 2001; Febbo and others 1999;
Makridakis and others 1997).
We hypothesized that if BMI increases BPH development through an
increase in the E to T ratio, then the risk should be higher for more obese men with
the reduced SRD5A2 activity, i.e., in men with the L variant genotype. In order to
evaluate the association between BPH and BMI, and to determine whether
polymorphisms in the SRD5A2 gene modified this association, we used data from a
cross-sectional study among Hispanics from a large urology clinic in Los Angeles,
California.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
3
MATERIALS AND METHODS
Study Subjects
Subjects in this study were Hispanic men between 60 and 84 years of age
who attended the urology clinic at the Los Angeles County / University of Southern
California (LAC/USC) Medical Center, Los Angeles, California between July 1999
and June 2002. Subjects with histopathological diagnosis of prostate cancer were
excluded from the analyses since we believed that cancer status might affect BMI.
All subjects signed a written informed consent, completed a self-administered
questionnaire and provided a 10ml blood sample. The study protocol was reviewed
and approved by the Institutional Review Board at the University of Southern
California.
Each participant completed a questionnaire that contained demographic
information and urinary symptoms. We used the American Urological Association
(AUA) symptom index (Barry and others 1992) for estimating the severity of urinary
symptoms for BPH. Each participant also had a digital rectal exam (DRE) and the
attending urologist assessed whether the prostate was enlarged, and the clinical
impression (i.e., normal, benign or suspicious) about the prostate gland. Biopsy was
performed for suspicious prostate mass to exclude prostate cancer. We then divided
the study subjects into three mutually exclusive groups based on their DRE
assessments and the AUA symptom score:
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
4
1. Normal Men: Men with normal prostates on DRE and an AUA symptom
score less than 9,
2. Asymptomatic BPH: men with an enlarged prostate, an AUA symptom score
less than 9 and no history of medication use for prostatism,
3. Symptomatic BPH: men with an enlarged prostate, who had an AUA
symptom score of 9 or more and/or reported medication use for prostatism.
A single BPH case group (referenced as “any BPH” henceforth) was also formed
by combining subjects with symptomatic BPH and asymptomatic BPH.
Exposure assessment
We calculated BMI (i.e., weight in kilograms/height in meter squared) from the
self-reported height and weight measurements. We used the World Health
Organization (WHO) classification to categorize BMI (WHO 2000) were men with
BMI less than 25 are considered normal weight, BMI between 25 and 29.9 are
considered overweight and those with BMI at or above 30 are considered obese.
Genotyping
Buffy coats were extracted from the peripheral blood sample that each
participant provided. Buffy coats and plasma were stored at -70° C until genotyping.
DNA was purified from the buffy coats for all subjects by using the Gentra
PureGene kit (Gentra Systems, Inc., Minneapolis, MN). The laboratory personnel
involved in genotyping were masked to the disease status of the subjects.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
5
V89L: We used forward primer S’-CGGCAGCCCCTCTCCCTC-S’ and the
reverse primer 55 -TGCGCTCCTGGACGCCGG-3’ and then used single strand
conformational polymorphism (SSCP) analysis as described by Makridakis et al.
(Makridakis and others 1997) to determine the genotype at V89L locus in the
SRD5A2 gene.
Missing genotypic data: We could not obtain V89L genotypic data on 14
subjects: 9 with symptomatic and 5 with asymptomatic BPH.
Clinical data
We attempted to obtain the transrectal ultrasound (TRUS) estimated prostate
volumes of the 250 BPH cases who attended the LAC/USC urology clinic.
However, the TRUS was performed for 105 (42%) BPH cases only.
Statistical Analysis
We used analysis of variance (GLM procedure in SAS) to compare the
demographic variables between normal men and men with BPH, symptomatic BPH
and asymptomatic BPH. In order to evaluate the association between BMI and BPH,
we calculated odds ratios (ORs) and 95% confidence intervals (CIs) from
unconditional logistic regression while adjusting for age (60-64, 65-69 and 70+
years), educational level (up to 10th grade, >10th grade), alcohol consumption (0, <1
and 1+drink/day) and cigarette smoking (non-, ex- and current-smoker).
Although we had genotypic data on A49T polymorphism, the variant
genotype was only present in 1 asymptomatic and 5 symptomatic BPH cases. We
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
also had genotypic data on (TA)„ dinucleotide repeat but the number of (TA)is
alleles were very few (n=l). So, we could not assess any effect modification by
A49T or (TA)n repeat polymorphisms. Therefore, we are reporting the gene-
environment interaction between BMI and V89L genotype in this paper.
We considered BMI into three categories (<25, 25-29.9 and 30+) and V89L
genotype into two categories ( W and VL/LL) to evaluate the statistical significance
of the gene-environment interaction. Likelihood ratio tests were performed to
estimate the p-value for the gene-environment interaction. All p-values were two-
sided. All analyses were performed with the Statistical Analysis System (SAS)
version 8.1 software package (SAS Institute Inc., Cary, NC).
RESULTS
Based on DRE exam findings, there were 30 men with normal prostates, and
250 men with any BPH (193 symptomatic and 57 asymptomatic BPH) cases (Table
1). There were no statistically significant differences in age, education, alcohol and
tobacco use between normal men and men with any of the BPH categories (Table 1).
Although in univariate analysis increasing age, alcohol intake (in previous 12
months), cigarette smoking and lower education were associated with increased risk
of any BPH, symptomatic BPH and asymptomatic BPH, none of the ORs reached
statistical significance (Table 2). As we have reported previously (Salam and others
2003), presence of the variant L allele at V89L loci in the SRD5A2 gene was
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
7
associated with increased risk of BPH. The alleles of the V89L genotype were in
Hardy-Weinberg equilibrium among normal men. The allele frequency was 0.76 for
the V allele and 0.24 for the variant L allele (data not shown).
Table 1: Descriptive statistics of the study population (n=280)._______________________________________
Normal Men Any BPH Symptomatic Asymptomatic
N=30 (%) N=250 (%) BPH BPH
______________________________________________________________ HN193 (%)_______ N=57 (%)
Age (years)
60-64 18 (60.0%) 132 (52.8%) 98 (50.8%) 34 (59.6%)
65-69 8 (26.7%) 63 (25.2%) 49 (25.4%) 14 (24.6%)
70+ 4 (13.3%) 55 (22.0%) 46 (23.8%) 9 (15.8%)
BMI categories (kg/m2 )
<25 9 (30.0%) 73 (29.2%) 58 (30.0%) 15 (26.3%)
25-29.9 12 (40.0%) 121 (48.4%) 97 (50.3%) 24 (42.1%)
30+ 9 (30.0%) 56 (22.4%) 38 (19.7%) 18 (31.6%)
Alcohol use (in previous 12 months)
Non-drinker 23 (76.7%) 187 (74.8%) 148 (76.7%) 39 (68.4%)
<1 drink/day 5 (16.7%) 47 (16.4%) 31 (16.1%) 10 (17.5%)
1+ drink/day 2 (6.6%) 22 (8.8%) 14 (7.2%) 8 (14.1%)
Smoking status
Never smoker 14 (46.7%) 125 (50.0%) 98 (50.8%) 27 (47.4%)
Ex-smoker 14 (46.7%) 101 (40.4%) 78 (40.4%) 23 (40.3%)
Current-smoker 2 (6.6%) 24 (9.6%) 17 (8.8%) 7 (12.3%)
Level of education
Up to 10 grade 27 (90.0%) 205 (82.0%) 161 (83.4%) 44 (77.2%)
> 10t h grade 3 (10.0%) 45 (18.0%) 32 (16.6%) 13 (22.8%)
SRD5A2 V89L genotype b
VV 15 (50.0%) 99 (42.0%) 82 (44.6%) 17 (32.7%)
VL 13 (43.3%) 106 (44.9%) 77 (41.8%) 29 (55.8%)
LL 2 (6.7%) 31 (13.1%) 25 (13.6%) 6 (11.5%)
“ All p-values (from pairwise comparisons using ANOVA) for any group of men with any, symptomatic and
asymptomatic BPH compared to normal men were >0.10.
b Numbers do not add up because of missing V89 L genotypic data from 9 symptomatic and 5 asymptomatic
BPH cases.
In multivariate analysis adjusting for age, educational level, alcohol
consumption and smoking status, there was no association between BMI and any
BPH, symptomatic or asymptomatic BPH (Table 3).
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
8
Table 2: Univariate odds ratios (ORs) and 95% confidence intervals (CIs) for any, symptomatic and
asymptomatic benign prostatic hyperplasia (BPH) associated with body mass index (BMI) and other potential
confounders.
Any BPH Symptomatic BPH Asymptomatic BPH
OR (95%CI) OR (95%CI) OR (95%CJ)
BMI categories (kg/m2 )
<25
25-29.9
30+
1.00
1.2 (0.5-3.1)
0.8 (0.3-2.1)
1.00
1.3 (0.5-3.2)
0.7 (0.2-1.8)
1.00
1.2 (0.4-3.5)
1.2 (0.4-3.8)
Age (years)
60-64
65-69
70+
1.00
1.1 (0.4-2.6)
1.9 (0.6-5.8)
1.00
1.1 (0.5-2.8)
2.1 (0.7-6.6)
1.00
0.9 (0.3-2.6)
1.2(03-4.4)
Alcohol use (in previous 12 months)
Never taken
<1 drink/day
1+ drink/day
1.00
1.0 (0.4-2.8)
1.4 (0.3-6.1)
1.00
1.0 (0.3-2.7)
1.1 (0.2-5.1)
1.00
1.2 (0.46-3.9)
2.4(0.5-12.1)
Smoking status
Never smoker
Ex-smoker
Current-smoker
1.00
0.8 (0,4-1.8)
1.3 (0.3-6.3)
1.00
0.8 (0.4-1.8)
1.2 (0.3-5.8)
1.00
0.9 (0.3-2.2)
1.8 (0.3-9.9)
Level of education
Up to 10t h grade
> 10* grade
1.00
2.0 (0.6-6.8)
1.00
1.8 (0.5-6.3)
1.00
2.7 (0.7-10.2)
SRD5A2 V89L genotype
w
VL/LL
1.00
1.4 (0.7-3.0)
1.00
1.2 (0.6-2.7)
1.00
2.1 (0.8-5.2)
Table 3: Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for any, symptomatic and
asymptomatic benign prostatic hyperplasia (BPH) associated with body mass index (BMI).
Any BPH Symptomatic BPH Asymptomatic BPH
OR (95%CI) “ OR (95%C!) ® OR (95%CI) “
BMI categories (kg/m2 )
<25 1.00 1.00 1.00
25-29.9 1.3 (0.5-3.3) 1.3 (0.5-3.4) 1.0(03-3.1)
>30 0.8 (0.3-2.3) 0.7 (0.3-2.0) 1.2 (0.4-3.8)
P trend
0.69 0.49 0.77
0 ORs adjusted for age (60-64, 65-69, 70+ years), educational status (<10th grade, >10* grade),
alcohol use (0, <1, 1+ drink/day), and smoking status (never, ex- and current-smoker).
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
However, we found some evidence that the effect of BMI on BPH varied by
V89L genotype (Table 4). Although none of the point estimates were statistically
significant, our results suggested that overweight and obese men with W genotype
had reduced risk of any BPH, symptomatic BPH and asymptomatic BPH, while
overweight and obese men with the VL/LL genotypes had elevated risk of any BPH
(p-value for gene-environment interaction for any BPH = 0.14). The test for
interaction was strongest when the analysis was restricted to asymptomatic BPH
cases (p-value for gene-environment interaction = 0.06).
Table 4: Odds ratios (ORs) and 95% confidence intervals (CIs) for any, symptomatic and
asymptomatic benign prostatic hyperplasia (BPH) associated with body mass index (BMI) stratified
by V89L polymorphism in the steroid 5-a reductase type 2 (SRD5A2) gene.____________________
Normal men AnyBPH Symptomatic BPH Asymptomatic BPH
N N OR" (95% Cl) N OR" (95% Cl) N OR" (95% Cl)
Among men with VVgenotype
BMI categories
<25 2 28 1.00 23 1.00 5 1.00
25-29.9 8 50 0.4 (0.1-2.1) 45 0.4 (0.1-2.4) 5 0.1 (0.1-0.9)
>30 5 21 0.3 (0.1-1.7) 14 0.2 (0.1-1.4) 7 0.2 (0.1-3.3)
Ptrend
0.18 0.10 0.75
Among men with VL/LL genotype
BMI categories
<25 7 41 1.00 32 1.00 9 1.00
25-29.9 4 63 3.4 (0.9-13.3) 47 3.0(0.7-11.8) 16 4.3 (0.6-28.9)
>10 4 33 1.7 (0.4-6.6) 23 1.5(0.4-6.2) 10 1.9(0.3-10.4)
P trend
0.46 0.55 0.50
P-value for gene-environment 0.14 0.18 0.06
interaction
" ORs adjusted for age (60-64, 65-69, 70+ years), educational status (<10th grade, >10t h grade),
alcohol use (0, <1, 1+ drink/day), and smoking status (never, ex- and current-smoker).
DISCUSSION
In this study, we Investigated the role of BMI in the development of BPH in
Hispanics. We found no association between BMI and BPH overall, however our
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
10
results suggest a gene-environment interaction between BMI and the V89L
polymorphism in the SRD5A2 gene in the development of BPH. Our results showed
that higher BMI was associated with reduced BPH risk in men with the VV genotype,
whereas BPH risk increased with higher BMI in men with the VL or LL genotypes.
Epidemiologic studies have defined BPH cases differently and the role of
obesity for BPH is yet to be firmly established. Some of the studies defined BPH
cases based on surgery for BPH (Dahle and others 2002; Giovannucci and others
1994; Morrison 1992; Seitter and Barrett-Connor 1992; Signorello and others 1999).
This may not be an ideal outcome definition, since subjects who opt for surgery
might differ from those who do not and as such do not represent the ‘true5 case
population. Two cross-sectional studies even defined BPH cases based on
participants5 responses to having any ‘prostatic disorder5 (Fernandez and others
1992; Porta and others 1994). Moreover, majority of the studies did not perform any
DRE or TRUS to determine prostate size in controls to exclude the presence of
asymptomatic BPH in controls (Dahle and others 2002; Daniell 1993; Giovannucci
and others 1994; Lee and others 1997; Morrison 1992; Seitter and Barrett-Connor
1992; Signorello and others 1999). This may have led to the inclusion of
asymptomatic BPH cases within the control population and resulted in a null
association between BMI and BPH. On the contrary, the two prospective studies that
performed DRE and evaluated urinary symptoms in control population observed a
statistically significant inverse association between BMI and risk of BPH (Glynn and
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
11
others 1985) and a higher incidence of surgery for BPH with lower BMI (Sidney and
others 1991). Our results are consistent with these two studies.
In a prospective study by Gann et al. (Gann and others 1995), it was shown
that both an increase in estrogen and a decrease in androgen levels are required for
prostatic hyperplasia, and BPH risk increased only among men with high plasma
estradiol (E2) with low plasma T levels. Our finding of a putative interaction
between BMI and the SRD5A2 genotype is consistent with this since serum E levels
would be expected to increase with obesity, and men with the VL/LL genotype would
be expected to have lower than normal intraprostatic DHT levels. The resultant
increase in the E : DHT ratio would be expected to result in the increased BPH risk,
just as we observed.
However, in overweight and obese men with W genotype, although serum E
levels are increasing because of obesity, the enzymatic activity of the SRD5A2
remains unaltered and conversion of T to DHT remained unaffected. This could
explain why obese men with the VV genotype are not at higher risk ofBPH. We have
no explanation for the apparent inverse association between BMI and BPH in men
with the VV genotype.
A limitation to our study was the cross-sectional design having prevalent and
hospital-based rather than incident cases with BPH. Self-reported height and weight
may not be accurate and disease status may also affect body weight and as such
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
12
BMI. However, this misclassification in BMI assessment would have been non-
differential and biased the results towards the null.
Finally, our definition of BPH was based on a combination of the AUA
symptom score and a clinical exam. A limitation to our study was that the clinical
exams were conducted by a number of different clinicians. The resulting
misclassification of prostate size, would however, most likely have been
nondifferential and therefore would have biased our findings towards the null.
Epidemiological studies have used different criteria to define BPH (Bosch and others
1995; Garraway and others 1991; Girman and others 1999; Roberts and others 1997)
and to date there is no agreement about the case definition of BPH. Our cutoff
weight of 30 grams has been found to be a sensitive measure of BPH (Bosch and
others 1995). Our DRE estimates also appear to be valid, since 98 out of the 105
men with BPH (i.e., 93.3%) on whom we could obtain the TRUS estimated prostate
size had a prostate weight of 30 grams or more. Those with prostate weighing less
than 30 grams on TRUS (n=7) had prostate biopsy that revealed BPH. These results
suggest that our definition of BPH did not lead to any diagnostic bias. A strength of
our study is that the controls were all examined so that we separated the BPH cases
from the control population.
In conclusion, our results suggest that BMI and androgen metabolism genes
are important determinants for BPH, and that they should be studied in context with
each other.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
13
BIBLIOGRAPHY
Allen. NE, Forrest MS, Key TJ. 2001. The association between polymorphisms in the
CYP17 and 5a~reductase (SRD5A2) genes and serum androgen
concentrations in men. Cancer Epidemiol Biomarkers PrevlG(3):185-9.
Barry MI, Fowler FJ, Jr., O'Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK,
Cockett AT. 1992. The American Urological Association symptom index for
benign prostatic hyperplasia. The Measurement Committee of the American
Urological Association. J Urol 148(5):1549-57.
Bosch JL, Hop WC, Kirkels WJ, Schroder FH. 1995. Natural history of benign
prostatic hyperplasia: appropriate case definition and estimation of its
prevalence in the community. Urology 46(3 Suppl A):34-40.
Dahle SE, Chokkalingam AP, Gao YT, Deng J, Stanczyk FZ, Hsing AW. 2002.
Body size and serum levels of insulin and leptin in relation to the risk of
benign prostatic hyperplasia. J Urol 168(2):599-604.
Daniell HW. 1993. Larger prostatic adenomas in obese men with no associated
increase in obstructive uropathy. J Urol 149(2):315-7.
di Salle E, Giudici D, Radice A, Zaccheo T, Omati G, Nesi M, Panzer! A, Delos S,
Martin PM. 1998. PNU 157706, a novel dual type I and II 5a-reductase
inhibitor. J Steroid Biochem Mol Biol 64(3-4): 179-86.
Febbo PG, Kantoff PW, Platz EA, Casey D, Batter S, Giovannucci E, Hennekens
CH, Stampfer Ml. 1999. The V89L polymorphism in the 5a-reductase type 2
gene and risk of prostate cancer. Cancer Res 59(23):5878-81.
Fernandez E, Porta M, Alonso J, Anto JM. 1992. Epidemiology of prostatic disorders
in the city of Barcelona. Int J Epidemiol 21(5):959-65.
Gann PH, Hennekens CH, Longcope C, Verhoek-Oftedahl W, Grodstein F, Stampfer
MJ. 1995. A prospective study of plasma hormone levels, nonhormonal
factors, and development of benign prostatic hyperplasia. Prostate 26(l):40-9.
Garraway WM, Collins GN, Lee RJ. 1991. High prevalence of benign pro static
hypertrophy in the community. Lancet 338(8765):469-71.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
14
Giovannucci E, Rimm EB, Chute CG, Kawachi I, Colditz GA, Stampfer MJ, Willett
WC. 1994. Obesity and benign prostatic hyperplasia. Am J Epidemiol
140(11):989-1002.
Girman CJ. 1998. Population-based studies of the epidemiology of benign prostatic
hyperplasia. Br J Urol 82 Suppl 1:34-43.
Girman Cl, Jacobsen SJ, Rhodes T, Guess HA, Roberts RO, Lieber MM. 1999.
Association of health-related quality of life and benign prostatic enlargement.
Eur Urol 35(4):277-84.
Glynn RJ, Campion EW, Bouchard GR, Silbert JE. 1985. The development of
benign prostatic hyperplasia among volunteers in the Normative Aging
Study. Am J Epidemiol 121(l):78-90.
Guess HA. 1992. Benign prostatic hyperplasia: antecedents and natural history.
Epidemiol Rev 14:131-53.
Guess HA. 2001. Benign prostatic hyperplasia and prostate cancer. Epidemiol Rev
23(1): 152-8.
Krieg M, Nass R, Tunn S. 1993. Effect of aging on endogenous level of 5 a-
dihydrotestosterone, testosterone, estradiol, and estrone in epithelium and
stroma of normal and hyperplastic human prostate. J Clin Endocrinol Metab
77(2):375-81.
Lee E, Park MS, Shin C, Lee H, Yoo K, Kim Y, Shin Y, Paik HY, Lee C. 1997. A
high-risk group for prostatism: a population-based epidemiological study in
Korea. Br J Urol 79(5):736-41.
Levine AC, Kirschenbaum A, Gabrilove JL. 1997. The role of sex steroids in the
pathogenesis and maintenance of benign prostatic hyperplasia. Mt Sinai J
Med 64(l):20-5.
Makridakis N, Ross RK, Pike MC, Chang L, Stanczyk FZ, Kolonel LN, Shi CY, Yu
MC, Henderson BE, Reichardt JK. 1997. A prevalent missense substitution
that modulates activity of prostatic steroid 5a-reductase. Cancer Res
57(6): 1020-2.
Makridakis NM, di Salle E, Reichardt JK. 2000. Biochemical and pharmacogenetic
dissection of human steroid 5 cc-reductase type II. Pharmacogenetics
10(5):4Q7-13.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
15
McConnell ID. 1990. Androgen ablation and blockade in the treatment of benign
prostatic hyperplasia. Urol Clin North Am 17(3):661-70.
Morrison AS. 1992. Risk factors for surgery for prostatic hypertrophy. Am J
Epidemiol 135(9):974-80.
Porta M, Fernandez E, Alonzo J, Anto JM. 1994. Re: Risk factors for benign
prostatic hypertrophy. Am I Epidemiol 139(1): 114-5.
Roberts RO, Jacobsen SJ, Rhodes T, Girman CJ, Guess HA, Lieber MM. 1997.
Natural history of prostatism: impaired health states in men with lower
urinary tract symptoms. J Urol 157(5);1711-7.
Salam MT, Ursin G, Skinner EC, Dessissa T, Reichardt JKV. 2003. Associations
between Polymorphisms in the Steroid 5-a Reductase Type II (SRD5A2)
Gene and Benign Prostatic Hyperplasia and Prostate Cancer, [abstract]. Am J
Hum Genet 73(5 Suppl):374.
Seitter WR, Barrett-Connor E. 1992. Cigarette smoking, obesity, and benign
prostatic hypertrophy: a prospective population-based study. Am J Epidemiol
135(5):500-3.
Shibata Y, Ito K, Suzuki K, Nakano K, Fukabori Y, Suzuki R, Kawabe Y, W onma S,
Yamanaka H. 2000. Changes in the endocrine environment of the human
prostate transition zone with aging: simultaneous quantitative analysis of
prostatic sex steroids and comparison with human prostatic histological
composition. Prostate 42(l):45-55.
Sidney S, Quesenberry C, Jr., Sadler MC, Lydick EG, Guess HA, Cattolica EV.
1991. Risk factors for surgically treated benign prostatic hyperplasia in a
prepaid health care plan. Urology 38(1 Suppl):13-9.
Signorello LB, Tzonou A, Lagiou P, Samoli E, Zavitsanos X, Trichopoulos D. 1999.
The epidemiology of benign prostatic hyperplasia: a study in Greece. BJU Int
84(3):286-91.
Tchemof A, Despres JP. 2000. Sex steroid hormones, sex hormone-binding globulin,
and obesity in men and women. Horni Metab Res 32(11-12):526-36.
Walsh PC. 1988. The role of estrogen/androgen synergism in the pathogenesis of
benign prostatic hyperplasia. J Urol 139(4):826.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
16
[WHO] World Health Organization. 2000. Obesity: preventing and managing the
global epidemic. Report of a WHO consultation on obesity. Geneva: World
Health Organization. Report nr Technical Report Series, No 894.
Ziada A, Rosenblum M, Crawford ED. 1999. Benign prostatic hyperplasia: an
overview. Urology 53(3 Suppl 3a): 1-6.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.

Linked assets

University of Southern California Dissertations and Theses

Conceptually similar

PDF

Determinants of mammographic density in African-American, non-Hispanic white and Hispanic white women before and after the diagnosis with breast cancer

PDF

BRCA1 mutations and polymorphisms in African American women with a family history of breast cancer identified through high throughput sequencing

PDF

A descriptive analysis of medication use by asthmatics in the Children's Health Study, 1993

PDF

beta3-adrenergic receptor gene Trp64Arg polymorphism and obesity-related characteristics among African American women with breast cancer: An analysis of USC HEAL Study

PDF

Family history, hormone replacement therapy and breast cancer risk on Hispanic and non-Hispanic women, The New Mexico Women's Health Study

PDF

Extent, prevalence and progression of coronary calcium in four ethnic groups

PDF

Development and evaluation of standardized stroke outcome measures in a population of stroke patients in rural China

PDF

A pilot survey of medical abortion knowledge and practices among obstetrician/gynecologists and family practitioners in Los Angeles County

PDF

Association between latchkey status and smoking behavior in middle school children

PDF

Evaluation of the accuracy and reliability of self-reported breast, cervical, and ovarian cancer incidence in a large population-based cohort of native California twins

PDF

Comparisons of metabolic factors among gestational diabetes mellitus probands, siblings and cousins

PDF

Dietary fiber intake and atherosclerosis progression: The Los Angeles Atherosclerosis Study

PDF

A linear model for measurement errors in oligonucleotide microarray experiment

PDF

A case-control study of passive smoking and bladder cancer risk in Los Angeles

PDF

Effect of hormone therapy on the progression of carotid-artery atherosclerosis in postmenopausal women with and without established coronary artery disease

PDF

Descriptive epidemiology of thyroid cancer in Los Angeles County, 1972-1995

PDF

A large-scale genetic association study of prostate cancer in a multi-ethnic population

PDF

Predictive value of CT coronary artery calcium scanning for coronary heart disease in asymptomatic subjects with diabetes mellitus

PDF

Polymorphisms in genes involved in steroid hormone metabolism and mammographic density changes in women randomized to menopausal estrogen and progesterone therapy

PDF

The association between recreational physical activity and mammographic density

Asset Metadata

Creator Salam, Md. Towhid (author)

Core Title Association between body mass and benign prostatic hyperplasia in Hispanics: Role of steroid 5-alpha reductase type 2 (SRD5A2) gene

School Graduate School

Degree Master of Science

Degree Program Applied Biostatistics and Epidemiology

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

Tag biology, biostatistics,health sciences, public health,OAI-PMH Harvest

Language English

Contributor Digitized by ProQuest (provenance)

Advisor Ursin, Giske (committee chair), Gilliland, Frank (committee member), Goran, Michael (committee member)

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c16-315742

Unique identifier UC11326966

Identifier 1420397.pdf (filename),usctheses-c16-315742 (legacy record id)

Legacy Identifier 1420397.pdf

Dmrecord 315742

Document Type Thesis

Rights Salam, Md. Towhid

Type texts

Source University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

Access Conditions 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...

Repository Name University of Southern California Digital Library

Repository Location USC Digital Library, University of Southern California, University Park Campus, Los Angeles, California 90089, USA