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Timothy J Key

Publications and source records attributed to Timothy J Key.

At least 37 records · Page 2Linked to original sources
PubMed2004

Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer And Nutrition (EPIC).

The evidence for anthropometric factors influencing breast cancer risk is accumulating, but uncertainties remain concerning the role of fat distribution and potential effect modifiers. We used data from 73,542 premenopausal and 103,344 postmenopausal women from 9 European countries, taking part in the EPIC study. RRs from Cox regression models were calculated, using measured height, weight, BMI and waist and hip circumferences; categorized by cohort-wide quintiles; and expressed as continuous variables, adjusted for study center, age and other risk factors. During 4.7 years of follow-up, 1,879 incident invasive breast cancers were identified. In postmenopausal women, current HRT modified the body size-breast cancer association. Among nonusers, weight, BMI and hip circumference were positively associated with breast cancer risk (all ptrend < or = 0.002); obese women (BMI > 30) had a 31% excess risk compared to women with BMI < 25. Among HRT users, body measures were inversely but nonsignificantly associated with breast cancer. Excess breast cancer risk with HRT was particularly evident among lean women. Pooled RRs per height increment of 5 cm were 1.05 (95% CI 1.00-1.16) in premenopausal and 1.10 (95% CI 1.05-1.16) in postmenopausal women. Among premenopausal women, hip circumference was the only other measure significantly related to breast cancer (ptrend = 0.03), after accounting for BMI. In postmenopausal women not taking exogenous hormones, general obesity is a significant predictor of breast cancer, while abdominal fat assessed as waist-hip ratio or waist circumference was not related to excess risk when adjusted for BMI. Among premenopausal women, weight and BMI showed nonsignificant inverse associations with breast cancer.

Abdomen↗
PubMed2004

Amount of DNA in plasma and cancer risk: a prospective study.

Levels of plasma DNA concentrations in cancer patients have been shown to be higher than the plasma DNA concentrations found in healthy subjects. The value of plasma DNA levels for development of neoplastic or pulmonary disease was evaluated in a large prospective study. Plasma samples (n = 1,184) were analyzed from 776 controls, 359 cases of cancer (lung, bladder, oral cavity, pharynx, larynx, leukemia) and 49 deaths from chronic obstructive pulmonary disease (COPD), including never smokers and ex-smokers, from 9 countries across Europe. The amount of plasma DNA was variable across the European Prospective Investigation into Cancer and Nutrition (EPIC) centers. High DNA concentrations in some centers might be due to the type of population recruited and/or the treatment of the samples. An elevated and statistically significant odds ratio (OR) was found for COPD deaths (OR = 2.53; 95% CI = 1.06-6.02), while nonsignificant increased ORs were present for oral cancers, cancers of the pharynx and larynx and leukemia. When the analyses were stratified by time since recruitment (below or above 36 months), the increased ORs were limited to the more recent period of recruitment, i.e., a time elapsed between blood drawing and disease onset lower than 36 months. This was particularly true for COPD deaths (OR = 12.7; 95% CI = 1.57-103) and leukemia (OR = 2.37; 95% CI = 1.20-4.67).

Adult↗
PubMed2004

Melatonin and breast cancer: a prospective study.

BACKGROUND: Experimental data from animals suggest a protective role for the pineal hormone melatonin in the etiology of breast cancer, but results from the few retrospective case-control studies that examined the association in humans have been inconsistent. To determine whether low levels of endogenous melatonin are associated with an increased risk for developing breast cancer, we conducted a prospective nested case-control study among British women. METHODS: Concentrations of 6-sulfatoxymelatonin, the main metabolite of melatonin in urine and a validated marker of circulating melatonin levels, were measured by radioimmunoassay in 24-hour urine samples collected from women shortly after enrollment in the prospective Guernsey III Study. Levels of 6-sulfatoxymelatonin were compared among 127 patients diagnosed with breast cancer during follow-up and among 353 control subjects, matched for age, recruitment date, menopausal status, and day of menstrual cycle for premenopausal women or number of years postmenopausal for postmenopausal women. Associations were examined by analyses of covariance and conditional logistic regression. All tests of statistical significance were two-sided. RESULTS: No statistically significant differences in urinary 6-sulfatoxymelatonin concentrations were observed between women who developed breast cancer and control subjects among premenopausal or postmenopausal women (P=.8 and P=.9, respectively). When data from premenopausal and postmenopausal women were combined in a multivariable analysis adjusted for potential confounders and grouped into three categories defined by 6-sulfatoxymelatonin tertiles of control subjects, the level of 6-sulfatoxymelatonin excreted was not statistically significantly associated with the risk of breast cancer (odds ratio [OR] for breast cancer = 0.95, 95% confidence interval [CI] = 0.55 to 1.65, comparing the middle category with the lowest category of 6-sulfatoxymelatonin concentration, and OR = 0.99, 95% CI = 0.58 to 1.70, comparing the highest category with the lowest category). CONCLUSION: We found no evidence that the level of melatonin is strongly associated with the risk for breast cancer.

Adult↗
PubMed2004

Fruits and vegetables and prostate cancer: no association among 1104 cases in a prospective study of 130544 men in the European Prospective Investigation into Cancer and Nutrition (EPIC).

We examined the association between self-reported consumption of fruits and vegetables and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Data on food consumption and complete follow-up for cancer incidence were available for 130544 men in 7 countries recruited into EPIC between 1993 and 1999. After an average of 4.8 years of follow-up, there were 1104 incident cases of prostate cancer. The associations of consumption of total fruits, total vegetables, cruciferous vegetables and combined total fruits and vegetables with prostate cancer risk were examined using Cox regression, stratified for recruitment center and adjusted for height, weight and energy intake. There was a wide range in consumption of fruits and vegetables: mean intakes (g/day) in the bottom and top fifths of the distribution, as estimated from 24-hr recalls in a subsample of participants, were 53.2 and 410.7 for fruits, 97.1 and 242.1 for vegetables and 169.0 and 633.7 for fruits and vegetables combined. No significant associations between fruit and vegetable consumption and prostate cancer risk were observed. Relative risks (95% confidence intervals) in the top fifth of the distribution of consumption, compared to the bottom fifth, were 1.06 (0.84-1.34) for total fruits, 1.00 (0.81-1.22) for total vegetables and 1.00 (0.79-1.26) for total fruits and vegetables combined; intake of cruciferous vegetables was not associated with risk. These results suggest that total consumption of fruits and vegetables is not associated with the risk for prostate cancer.

Adult↗
PubMed2004

A prospective study of diet and prostate cancer in Japanese men.

BACKGROUND AND AIMS: It has been hypothesized that some aspect of a traditional 'Asian' diet, that is low in animal products and high in soya, may be associated with a reduced risk of prostate cancer. This study aimed to examine the association between dietary intake and prostate cancer risk among 18,115 men in Hiroshima and Nagasaki, Japan, using prospective data from the Life Span Study. METHODS: Subjects completed a food-frequency questionnaire at baseline (1963, 1965 and/or 1979) and were followed for incident prostate cancer until the end of 1996. During this time, 196 incident prostate cancer cases were identified after 252,602 person-years of observation. Poisson regression was used to calculate incidence rates for each dietary factor after adjustment for age, calendar period, city of residence, radiation dose and education level. RESULTS: Fish intake was significantly associated with an increased risk of prostate cancer; men who consumed fish more than four times per week had a 54 increased risk of developing prostate cancer compared with men who ate fish less than twice per week (RR = 1.54; 95% CI, 1.03-2.31). No other food items, including soya products, were significantly associated with prostate cancer risk. CONCLUSIONS: These data suggest that dietary factors may not be strong determinants of prostate cancer in these Japanese men, although the increased risk associated with a high consumption of fish warrants further study.

Adolescent↗
PubMed2004

Nutrition and lifestyle in relation to bowel movement frequency: a cross-sectional study of 20630 men and women in EPIC-Oxford.

OBJECTIVE: To investigate the relationships between nutritional and lifestyle factors and bowel movement frequency. DESIGN: Cross-sectional analysis using data from a prospective study. Mean numbers of bowel movements were calculated in relation to a range of factors. In addition, individuals were categorised according to frequency of bowel movements: fewer than 7 per week ('less than daily') versus 7 or more per week ('daily'), and odds ratios were calculated from logistic regression models. Results for each factor were adjusted for the other factors under consideration. SETTING: The European Prospective Investigation into Cancer and Nutrition, Oxford cohort (EPIC-Oxford), UK. PARTICIPANTS: In total, 20630 men and women aged 22-97 years at recruitment. Thirty per cent of the subjects were vegetarians or vegans. RESULTS: Women had fewer bowel movements on average than men, and were less likely to have daily bowel movements. Mean bowel movement frequency was higher in vegetarians (10.5 in men, 9.1 in women) and especially in vegans (11.6 in men, 10.5 in women) compared with participants who ate meat (9.5 in men, 8.2 in women). There were also significant positive associations between bowel movement frequency and body mass index (BMI), intakes of dietary fibre and non-alcoholic fluids, for both men and women. Vigorous exercise was positively associated with bowel movement frequency in women although results for men were less clear. Alcohol intake was positively associated with bowel movement frequency in men but not in women. CONCLUSION: Being vegetarian and especially vegan is strongly associated with a higher frequency of bowel movements. Moreover, having a high intake of dietary fibre and fluids and a high BMI are associated with an increase in frequency of bowel movements.

Adult↗
PubMed2004

Diet, nutrition and the prevention of cancer.

OBJECTIVE: To assess the epidemiological evidence on diet and cancer and make public health recommendations. DESIGN: Review of published studies, concentrating on recent systematic reviews, meta-analyses and large prospective studies. CONCLUSIONS AND RECOMMENDATIONS: Overweight/obesity increases the risk for cancers of the oesophagus (adenocarcinoma), colorectum, breast (postmenopausal), endometrium and kidney; body weight should be maintained in the body mass index range of 18.5-25 kg/m(2), and weight gain in adulthood avoided. Alcohol causes cancers of the oral cavity, pharynx, oesophagus and liver, and a small increase in the risk for breast cancer; if consumed, alcohol intake should not exceed 2 units/d. Aflatoxin in foods causes liver cancer, although its importance in the absence of hepatitis virus infections is not clear; exposure to aflatoxin in foods should be minimised. Chinese-style salted fish increases the risk for nasopharyngeal cancer, particularly if eaten during childhood, and should be eaten only in moderation. Fruits and vegetables probably reduce the risk for cancers of the oral cavity, oesophagus, stomach and colorectum, and diets should include at least 400 g/d of total fruits and vegetables. Preserved meat and red meat probably increase the risk for colorectal cancer; if eaten, consumption of these foods should be moderate. Salt preserved foods and high salt intake probably increase the risk for stomach cancer; overall consumption of salt preserved foods and salt should be moderate. Very hot drinks and foods probably increase the risk for cancers of the oral cavity, pharynx and oesophagus; drinks and foods should not be consumed when they are scalding hot. Physical activity, the main determinant of energy expenditure, reduces the risk for colorectal cancer and probably reduces the risk for breast cancer; regular physical activity should be taken.

Alcohol Drinking↗
PubMed2004

Accuracy of self-reported waist and hip measurements in 4492 EPIC-Oxford participants.

OBJECTIVE: To assess the accuracy of self-reported waist and hip circumferences and the waist-to-hip ratio (WHR) by comparison with measured waist and hip circumferences and WHR in a sample of middle-aged men and women. DESIGN: Analysis of measured and self-reported waist and hip data from participants in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford). PARTICIPANTS: Four thousand four hundred and ninety-two British men and women aged 35-76 years. RESULTS: Spearman's rank correlation coefficients between measured and self-reported waist, hip and WHR were 0.80, 0.74 and 0.44, respectively, for men and 0.83, 0.86 and 0.62 for women. Waist was underestimated, on average, by 3.1 (standard deviation (SD) 5.6) cm in men and 1.9 (SD 5.4) cm in women. The extent of underestimation was greater in participants with larger waists, older participants and women with greater body mass index (BMI). Hip was underestimated by a mean of 1.8 (SD 4.9) cm in men and 1.2 (SD 4.5) cm in women; the extent of underestimation was greater in participants with larger hip circumference and older participants. On average, WHR was underestimated by less than 2% by men and women; the extent of underestimation was greater among those with larger WHR, older people and those with greater BMI. Using self-reported values, the proportion of classification to the correct tertile was over 65% for waist and hip measurements. For WHR this proportion was 50% among men and 60% among women. CONCLUSIONS: Self-reported waist and hip measurements in EPIC-Oxford are sufficiently accurate for identifying relationships in epidemiological studies.

Adult↗
PubMed2004

Soy intake and blood cholesterol concentrations: a cross-sectional study of 1033 pre- and postmenopausal women in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Clinical trials have suggested that the intake of soy protein reduces blood cholesterol. Few studies have explored this relation in subjects who consume soy as part of their regular diet. OBJECTIVE: In this study, we investigated whether blood cholesterol concentrations are related to the intake of soyfoods in a cohort comprising subjects with a wide variation in soy intake. DESIGN: This cross-sectional study included 1033 pre- and postmenopausal women selected from the Oxford arm of the European Prospective Investigation into Cancer and Nutrition. The sample included 361 nonvegetarians, 570 vegetarians, and 102 vegans. Their dietary intake was assessed by using a food-frequency questionnaire. Anthropometric data, medical history, and lifestyle information were obtained with the use of a questionnaire, blood samples were obtained, and plasma total, LDL-, and HDL-cholesterol concentrations were measured. RESULTS: Soy-protein intake was inversely associated with total and LDL-cholesterol concentrations and with the ratio of total to HDL cholesterol but not with HDL-cholesterol concentrations. Mean plasma LDL-cholesterol concentrations in women with a soy-protein intake >/=6 g/d was 12.4% lower than that in women who consumed <0.5 g/d (P < 0.001). CONCLUSION: Moderate intakes of soyfoods as part of a regular diet are associated with favorable blood cholesterol concentrations.

Aged↗
PubMed2004

The prevalence and features of the polycystic ovary syndrome in an unselected population.

Notwithstanding the potential public health impact of the polycystic ovary syndrome (PCOS), estimates regarding its prevalence are limited and unclear. Between July 1998 and October 1999, 400 unselected consecutive premenopausal women (18-45 yr of age) seeking a preemployment physical at the University of Alabama at Birmingham were studied (223 Black, 166 White, and 11 of other races). Evaluation included a history and physical examination, a modified Ferriman-Gallwey hirsutism score, and serum screening for hyperandrogenemia, hyperprolactinemia, and 21-hydroxylase-deficient nonclassical adrenal hyperplasia. PCOS was diagnosed by the presence of the following: 1) oligoovulation, 2) hyperandrogenemia and/or hirsutism (modified Ferriman-Gallwey score > or = 6), and 3) the exclusion of related disorders. Confirmed PCOS was established in those individuals whose evaluation was complete and indicative of PCOS, and possible PCOS was established when the hormonal evaluation was not complete or was unavailable, but the clinical phenotype was otherwise suggestive of the disorder. The individual probability of PCOS in women with possible PCOS was assigned a weight based on the findings in similar subjects whose evaluation was complete, and the total number of PCOS cases arising from these individuals was calculated (i.e. individual probability of PCOS x total number of subjects in the group). The cumulative prevalence of PCOS in our population was 6.6% (26.5 of 400), including 15 subjects among the 347 women completing their evaluation and a calculated prevalence of 11.5 subjects among the remainder. The prevalence rates of PCOS for Black and White women were 8.0 and 4.8%, respectively, not significantly different. These data from a large representative unselected population support the concept that PCOS is the most common endocrine abnormality of reproductive-aged women in the United States.

Adolescent↗
PubMed2003

Oestrogen exposure and breast cancer risk.

Epidemiological and experimental evidence implicates oestrogens in the aetiology of breast cancer. Most established risk factors for breast cancer in humans probably act through hormone-related pathways, and increased concentrations of circulating oestrogens have been found to be strongly associated with increased risk for breast cancer in postmenopausal women. This article explores the evidence for the hypothesis that oestrogen exposure is a major determinant of risk for breast cancer. We review recent data on oestrogens and breast cancer risk, consider oestrogen-related risk factors and examine possible mechanisms that might account for the effects of oestrogen. Finally, we discuss how these advances might influence strategies for reducing the incidence of breast cancer.

Animals↗
PubMed2003

Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): an observational study.

BACKGROUND: Dietary fibre is thought to protect against colorectal cancer but this view has been challenged by recent prospective and intervention studies that showed no protective effect. METHODS: We prospectively examined the association between dietary fibre intake and incidence of colorectal cancer in 519978 individuals aged 25-70 years taking part in the EPIC study, recruited from ten European countries. Participants completed a dietary questionnaire in 1992-98 and were followed up for cancer incidence. Relative risk estimates were obtained from fibre intake, categorised by sex-specific, cohort-wide quintiles, and from linear models relating the hazard ratio to fibre intake expressed as a continuous variable. FINDINGS: Follow-up consisted of 1939011 person-years, and data for 1065 reported cases of colorectal cancer were included in the analysis. Dietary fibre in foods was inversely related to incidence of large bowel cancer (adjusted relative risk 0.75 [95% CI 0.59-0.95] for the highest versus lowest quintile of intake), the protective effect being greatest for the left side of the colon, and least for the rectum. After calibration with more detailed dietary data, the adjusted relative risk for the highest versus lowest quintile of fibre from food intake was 0.58 (0.41-0.85). No food source of fibre was significantly more protective than others, and non-food supplement sources of fibre were not investigated. INTERPRETATION: In populations with low average intake of dietary fibre, an approximate doubling of total fibre intake from foods could reduce the risk of colorectal cancer by 40%.

Adult↗
PubMed2003

Nutrition and breast cancer.

The major risk factors for breast cancer are hormone-related, and the only well-established diet-related risk factors for breast cancer are obesity and alcohol consumption. Obesity increases breast cancer risk in postmenopausal women by around 30%, probably by increasing serum concentrations of bioavailable oestradiol. Moderate alcohol intakes increase breast cancer risk by about 7% per alcoholic drink per day, perhaps also by increasing oestrogen levels. Populations with high fat intakes generally have high rates of breast cancer, but studies of individual women have not confirmed an association of high fat diets with breast cancer risk. Phyto-oestrogens can affect hormone metabolism, but data on phyto-oestrogen consumption and breast cancer risk are inconsistent. Nutrition might affect breast cancer risk by altering levels of growth factors such as insulin-like growth factor-I. Current dietary advice should be to avoid obesity, limit alcohol intake, and maintain a varied diet.

Alcohol Drinking↗
PubMed2003

Lifestyle determinants of serum insulin-like growth-factor-I (IGF-I), C-peptide and hormone binding protein levels in British women.

OBJECTIVE: This study aims to identify the lifestyle determinants of insulin-like growth factor-I (IGF-I) and its main binding proteins (IGFBPs), C-peptide, and sex hormone-binding globulin (SHBG) to help elucidate the mechanism through which lifestyle factors may affect cancer risk. METHODS: This study is based on a sample of 292 British women, aged 20-70 years, whose lifestyle characteristics were assessed using a self-administered questionnaire and whose serum hormone concentrations were measured using immunoassays. RESULTS: Age was a strong determinant of both IGF-I and IGFBP levels; women aged 65-70 years had significantly lower IGF-I and IGFBP-3 concentrations and significantly higher IGFBP-1 and IGFBP-2 concentrations than women aged 20-24 years. Body mass index (BMI) was not strongly associated with IGF-I, although women with a BMI of 26-27.9 kg/m2 had a higher IGF-I concentration compared with both lean (BMI <20 kg/m2) and obese (BMI 30+ kg/m2) women. However, obese women had a significantly higher C-peptide and IGFBP-3 concentration and a significantly lower IGFBP-1, IGFBP-2, and SHBG concentration compared with lean women. Increasing vigorous exercise was associated with a significantly lower C-peptide concentration and increasing leisure-time activity was associated with a significantly higher IGFBP-1 concentration. Other lifestyle factors such as job activity, smoking, and reproductive factors were not associated with any hormone. CONCLUSIONS: Our data show that age is a major determinant of both IGF-I and its main binding proteins in women. BMI has strong effects on IGFBPs, C-peptide, and SHBG, but its effects on IGF-I remain unclear. The possible effect of physical activity on IGFBP-1 requires further investigation.

Adult↗
PubMed2003

EPIC-Oxford: lifestyle characteristics and nutrient intakes in a cohort of 33 883 meat-eaters and 31 546 non meat-eaters in the UK.

OBJECTIVE: To describe the lifestyle characteristics and nutrient intakes of the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: Cohort of men and women recruited through general practices or by post to include a high proportion of non meat-eaters. Dietary, anthropometric and lifestyle data were collected at baseline and four diet groups were defined. SETTING: United Kingdom. PARTICIPANTS: In total, 65 429 men and women aged 20 to 97 years, comprising 33 883 meat-eaters, 10 110 fish-eaters, 18 840 lacto-ovo vegetarians and 2596 vegans. RESULTS: Nutrient intakes and lifestyle factors differed across the diet groups, with striking differences between meat-eaters and vegans, and fish-eaters and vegetarians usually having intermediate values. Mean fat intake in each diet group was below the UK dietary reference value of 33% of total energy intake. The mean intake of saturated fatty acids in vegans was approximately 5% of energy, less than half the mean intake among meat-eaters (10-11%). Vegans had the highest intakes of fibre, vitamin B1, folate, vitamin C, vitamin E, magnesium and iron, and the lowest intakes of retinol, vitamin B12, vitamin D, calcium and zinc. CONCLUSIONS: The EPIC-Oxford cohort includes 31 546 non meat-eaters and is one of the largest studies of vegetarians in the world. The average nutrient intakes in the whole cohort are close to those currently recommended for good health. Comparisons of the diet groups show wide ranges in the intakes of major nutrients such as saturated fat and dietary fibre. Such variation should increase the ability of the study to detect associations of diet with major cancers and causes of death.

Adult↗
PubMed2003

Mortality in British vegetarians: review and preliminary results from EPIC-Oxford.

BACKGROUND: Three prospective studies have examined the mortality of vegetarians in Britain. OBJECTIVE: We describe these 3 studies and present preliminary results on mortality from the European Prospective Investigation into Cancer and Nutrition-Oxford (EPIC-Oxford). DESIGN: The Health Food Shoppers Study and the Oxford Vegetarian Study were established in the 1970s and 1980s, respectively; each included about 11 000 subjects and used a short questionnaire on diet and lifestyle. EPIC-Oxford was established in the 1990s and includes about 56 000 subjects who completed detailed food frequency questionnaires. Mortality in all 3 studies was followed though the National Health Service Central Register. RESULTS: Overall, the death rates of all the subjects in all 3 studies are much lower than average for the United Kingdom. Standardized mortality ratios (95% CIs) for all subjects were 59% (57%, 61%) in the Health Food Shoppers Study, 52% (49%, 56%) in the Oxford Vegetarian Study, and 39% (37%, 42%) in EPIC-Oxford. Comparing vegetarians with nonvegetarians within each cohort, the death rate ratios (DRRs), adjusted for age, sex and smoking, were 1.03 (0.95, 1.13) in the Health Food Shoppers Study, 1.01 (0.89, 1.14) in the Oxford Vegetarian Study, and 1.05 (0.86, 1.27) in EPIC-Oxford. DRRs for ischemic heart disease in vegetarians compared with nonvegetarians were 0.85 (0.71, 1.01) in the Health Food Shoppers Study, 0.86 (0.67, 1.12) in the Oxford Vegetarian Study, and 0.75 (0.41, 1.37) in EPIC-Oxford. CONCLUSIONS: The mortality of both the vegetarians and the nonvegetarians in these studies is low compared with national rates. Within the studies, mortality for major causes of death was not significantly different between vegetarians and nonvegetarians, but the nonsignificant reduction in mortality from ischemic heart disease among vegetarians was compatible with the significant reduction previously reported in a pooled analysis of mortality in Western vegetarians.

Adult↗
PubMed2003

Association between two polymorphisms in the SRD5A2 gene and serum androgen concentrations in British men.

Androgens are essential for the growth of the prostate gland and have been implicated in the development of prostate cancer. Little is known about the determinants of androgen levels in men, although observed ethnic differences suggest they may have a genetic basis. Several polymorphisms have been identified in the steroid 5 alpha-reductase type II gene (SRD5A2), which encodes an enzyme that catalyzes the conversion of testosterone to its more potent metabolite, dihydrotestosterone. Although some of these polymorphisms have been associated with increased prostate cancer risk, the association with circulating androgen levels remains unclear. The purpose of this study is to investigate the association between the (TA)(n) dinucleotide repeat polymorphism in the 3' untranslated region and the A49T polymorphism (which replaces the normal alanine with threonine at codon 49) in the SRD5A2 gene and serum androgen concentrations in 604 British men. In particular, we wanted to test the hypotheses that the variant alleles are associated with an increased serum concentration of androstanediol glucuronide, a direct metabolite of dihydrotestosterone and a serum marker of 5 alpha-reductase activity. Mean hormone concentrations were evaluated in each genotype, and adjusted for age and other relevant factors. We found no evidence that the SRD5A2 (TA)(n) repeat polymorphism was associated with androgen levels. Men who possessed one or two copies of the variant T allele in the A49T polymorphism had a significantly 24% lower androstanediol glucuronide concentration than men who were homozygous for the wild-type allele (P = 0.0003). Because of the rarity of this variant allele, larger studies are needed to additionally clarify the role of the A49T polymorphism in androgen metabolism.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗