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Biomedical subjects

T J Key

Publications and source records attributed to T J Key.

At least 37 records · Page 2Linked to original sources

Epidemiology of breast cancer.

Breast cancer is the commonest cause of cancer death in women worldwide. Rates vary about five-fold around the world, but they are increasing in regions that until recently had low rates of the disease. Many of the established risk factors are linked to oestrogens. Risk is increased by early menarche, late menopause, and obesity in postmenopausal women, and prospective studies have shown that high concentrations of endogenous oestradiol are associated with an increase in risk. Childbearing reduces risk, with greater protection for early first birth and a larger number of births; breastfeeding probably has a protective effect. Both oral contraceptives and hormonal therapy for menopause cause a small increase in breast-cancer risk, which appears to diminish once use stops. Alcohol increases risk, whereas physical activity is probably protective. Mutations in certain genes greatly increase breast-cancer risk, but these account for a minority of cases.

Adult↗

Circulating levels of sex hormones and their relation to risk factors for breast cancer: a cross-sectional study in 1092 pre- and postmenopausal women (United Kingdom).

OBJECTIVE: To investigate the relationships between plasma concentrations of sex hormones and risk factors for breast cancer. METHODS: We investigated the relationship of plasma concentrations of estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) with breast cancer risk factors in 636 premenopausal and 456 postmenopausal women. Risk factor data were obtained from questionnaires and hormone concentrations measured by immunoassays; variations in geometric means were compared using analysis of covariance. RESULTS: SHBG decreased with increasing body mass index and increasing waist-hip ratio both in pre- and postmenopausal women. In postmenopausal women only, estradiol increased with increasing body mass index. In premenopausal women, estradiol decreased with increasing physical activity, estradiol was higher in current than in ex- and non-smokers, and FSH decreased with increasing alcohol intake. No associations were observed between sex hormones and age at menarche, parity, age at menopause, and previous use of oral contraceptives in either pre- or postmenopausal women. CONCLUSIONS: Certain factors such as obesity and perhaps waist-hip ratio, physical activity and alcohol consumption, but probably not age at menarche and parity, may mediate their effects on breast cancer risk by changing circulating concentrations of sex hormones.

Adult↗

Soya intake and plasma concentrations of daidzein and genistein: validity of dietary assessment among eighty British women (Oxford arm of the European Prospective Investigation into Cancer and Nutrition).

Soya products contain high levels of the isoflavones genistein and daidzein, and their glucosides, and may lower the risk of cardiovascular disease, osteoporosis and cancer. The present cross-sectional study investigated plasma concentrations of daidzein and genistein and their correlations with dietary soya consumption in four groups of twenty premenopausal British women. The women were selected from the Oxford arm of the European Prospective Investigation into Cancer and Nutrition using data from food-frequency questionnaires (FFQ) to guarantee a wide variation in soya consumption, and to investigate the utility of the question related to soya milk consumption compared with the utility of the question related to other soya foods. Dietary intakes of isoflavones were additionally assessed by 7 d food diaries. Plasma concentrations of daidzein and genistein were measured by time-resolved fluoroimmunoassay. Geometric mean plasma concentrations (nmol/l) were for the four groups, which were based on increasing soya intake, 4.9, 8.4, 39.2 and 132 for daidzein and 14.3, 16.5, 119 and 378 for genistein. The Spearman correlation coefficients for plasma isoflavone concentrations with estimated dietary intakes were between 0.66 and 0.80 for the diary-based estimates and between 0.24 and 0.74 for the FFQ-based estimates. The correlations for soya milk intakes were clearly higher than the correlations for intakes of other soya foods. We conclude that both the food diary and the FFQ estimate dietary soya isoflavone intakes sufficiently well to use them in epidemiological studies, and that plasma concentrations of daidzein and genistein in Western women who consumed soya products as a part of their regular diet were close to those in Asian populations.

Adult↗

Energy balance and cancer: the role of sex hormones.

Energy balance can affect the risk for hormone-related cancers by altering sex hormone levels. Energy intake and expenditure are difficult to measure in epidemiological studies, but a chronic excess of intake relative to expenditure leads to a high BMI, which can be accurately measured. In premenopausal women obesity has little effect on the serum concentration of oestradiol, but causes an increase in the frequency of anovular menstrual cycles and thus a reduction in progesterone levels; these changes lead to a large increase in the risk for endometrial cancer. but little change, or a small decrease, in the risk for breast cancer. In post-menopausal women oestradiol levels are not regulated by negative feedback, and obesity causes an increase in the serum concentration of bioavailable oestradiol; this factor causes increases in the risk for both endometrial cancer and breast cancer. The development of ovarian cancer appears to be related more strongly to the frequency of ovulation than to direct effects of circulating levels of sex hormones, and BMI is not clearly associated with the risk for ovarian cancer. In men, increasing BMI has little effect on bioavailable androgen levels, and any effect of obesity on prostate cancer risk is small.

Body Mass Index↗

Soy milk intake in relation to serum sex hormone levels in British men.

Soy beans contain high levels of the isoflavones genistein and daidzein and their glycosides and have been implicated in the prevention of prostate cancer, possibly via their effects on sex hormone metabolism. The aim of this study was to assess the relation between dietary soy intake and sex hormone levels in a cross-sectional analysis of 696 men with a wide range of soy intakes. Soy milk intake was measured using a validated semiquantitative food frequency questionnaire, and serum hormone concentrations were measured by immunoassay. Multiple regression was used to investigate the association between soy milk intake, an index of isoflavone intake, and hormone levels after adjustment for pertinent confounders. Soy milk intake was not associated with serum concentrations of testosterone, free testosterone, androstanediol glucuronide, sex hormone-binding globulin, or luteinizing hormone. These results suggest that soy milk intake, as a marker of isoflavone intake, is not associated with serum sex hormone concentrations among free-living Western men.

Adult↗

Soy milk intake and plasma sex hormones: a cross-sectional study in pre- and postmenopausal women (EPIC-Oxford).

Soy beans contain high levels of the isoflavones genistein and daidzein and their glucosides. We investigated the relationship between soy milk intake and plasma concentrations of estradiol, sex hormone-binding globulin, and, in premenopausal women, follicle-stimulating hormone, luteinizing hormone, and progesterone in a cross-sectional study of 636 premenopausal and 456 postmenopausal British women. Sixty-five percent of the women were vegetarians or vegans. Data on soy milk intake and other factors were obtained from a validated food frequency questionnaire, hormone concentrations were measured by immunoassays, and variations in geometric means were compared using analysis of covariance. We observed no statistically significant trends or meaningful associations between soy milk intake and circulating sex hormones. Adjusting for factors possibly affecting circulating hormone concentrations did not materially alter the results. We conclude that soy milk intake does not change plasma concentrations of sex hormones in pre- or postmenopausal British women who consume soy milk as a part of their regular diet.

Adult↗

The association between polymorphisms in the CYP17 and 5alpha-reductase (SRD5A2) genes and serum androgen concentrations in men.

Prospective studies suggest that prostate cancer risk may be increased in association with high serum concentrations of free testosterone and androstanediol glucuronide (A-diol-g). Polymorphisms have been identified in the 17-hydroxylase cytochrome P450 gene (CYP17) and the steroid 5alpha-reductase type II gene (SRD5A2), two genes that are involved in the biosynthesis and metabolism of androgens in men. The CYP17 MspA1 I polymorphism has been associated with increased prostate cancer risk, and the SRD5A2 V89L polymorphism has been associated with low A-diol-g in Asian men, a serum marker of 5alpha-reductase activity. The purpose of this study was to investigate the association between these two polymorphisms and serum sex hormone concentrations in 621 British men. In particular, we wanted to test the hypotheses that the A2 allele in the CYP17 gene is associated with increased serum testosterone concentrations, and the L allele in the SRD5A2 gene is associated with reduced A-diol-g concentrations. Mean hormone concentrations were evaluated in each genotype and adjusted for age and other relevant factors. We found no evidence that the CYP17 MspA1 I polymorphism was associated with higher testosterone levels. The L/L genotype of the SRD5A2 V89L polymorphism was associated with a 10% lower A-diol-g concentration, but this was not significant at the 5% level. However, the L/L genotype of the V89L polymorphism was associated with significantly lower concentrations of testosterone and free testosterone (by 12% and 16%, respectively) and an 8% higher sex hormone-binding globulin concentration. These results suggest that the CYP17 MspA1 I polymorphism is not associated with testosterone concentrations and that the SRD5A2 V89L polymorphism is not a strong determinant of A-diol-g concentration in Caucasian men.

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

Health benefits of a vegetarian diet.

Compared with non-vegetarians, Western vegetarians have a lower mean BMI (by about 1 kg/m2), a lower mean plasma total cholesterol concentration (by about 0.5 mmol/l), and a lower mortality from IHD (by about 25%). They may also have a lower risk for some other diseases such as constipation, diverticular disease, gallstones and appendicitis. No differences in mortality from common cancers have been established. There is no evidence of adverse effects on mortality. Much more information is needed, particularly on other causes of death, other morbidity including osteoporosis, and long-term health in vegans. The evidence available suggests that widespread adoption of a vegetarian diet could prevent approximately 40,000 deaths from IHD in Britain each year.

Body Mass Index↗

Endogenous sex hormones and prostate cancer: a quantitative review of prospective studies.

This paper presents a quantitative review of the data from eight prospective epidemiological studies, comparing mean serum concentrations of sex hormones in men who subsequently developed prostate cancer with those in men who remained cancer free. The hormones reviewed have been postulated to be involved in the aetiology of prostate cancer: androgens and their metabolites testosterone (T), non-SHBG-bound testosterone (non-SHBG-bound T), di-hydrotestosterone (DHT), androstanediol glucuronide (A-diol-g), androstenedione (A-dione), dehydroepiandrosterone sulphate (DHEAS), sex hormone binding globulin (SHBG), the oestrogens, oestrone and oestradiol, luteinizing hormone (LH) and prolactin. The ratio of the mean hormone concentration in prostate cancer cases to that of controls (and its 95% confidence interval (CI)) was calculated for each study, and the results summarized by calculating the weighted average of the log ratios. No differences in the average concentrations of the hormones were found between prostate cancer cases and controls, with the possible exception of A-diol-g which exhibited a 5% higher mean serum concentration among cases relative to controls (ratio 1.05, 95% CI 1.00-1.11), based on 644 cases and 1048 controls. These data suggest that there are no large differences in circulating hormones between men who subsequently go on to develop prostate cancer and those who remain free of the disease. Further research is needed to substantiate the small difference found in A-diol-g concentrations between prostate cancer cases and controls.

Adult↗

Oestradiol and sex hormone-binding globulin in premenopausal and post-menopausal meat-eaters, vegetarians and vegans.

Endogenous oestradiol is strongly associated with breast cancer risk but its determinants are poorly understood. To test the hypothesis that vegetarians have lower plasma oestradiol and higher sex hormone-binding globulin (SHBG) than meat-eaters we assayed samples from 640 premenopausal women (153 meat-eaters, 382 vegetarians, 105 vegans) and 457 post-menopausal women (223 meat-eaters, 196 vegetarians, 38 vegans). Vegetarians and vegans had lower mean body mass indices (BMI) and lower plasma cholesterol concentrations than meat-eaters, but there were no statistically significant differences between meat-eaters, vegetarians and vegans in pre- or post-menopausal plasma concentrations of oestradiol or SHBG. Before adjusting for BMI there were small differences in the direction expected, with the vegetarians and vegans having higher SHBG and lower oestradiol (more noticeable amongst post-menopausal women) than the meat-eaters. These small differences were essentially eliminated by adjusting for BMI. Thus this study implies that the relatively low BMI of vegetarians and vegans does cause small changes in SHBG and in post-menopausal oestradiol, but that the composition of vegetarian diets may not have any additional effects on these hormones.

Adult↗

Soya foods and breast cancer risk: a prospective study in Hiroshima and Nagasaki, Japan.

The association between soya foods and breast cancer risk was investigated in a prospective study of 34759 women in Hiroshima and Nagasaki, Japan. Women completed dietary questionnaires in 1969-1970 and/or in 1979-1981 and were followed for incident breast cancer until 1993. The analysis involved 427 cases of primary breast cancer in 488989 person-years of observation. The risk for breast cancer was not significantly associated with consumption of soya foods: for tofu, relative risks adjusted for attained age, calendar period, city, age at time of bombings and radiation dose to the breast were 0.99 (95% CI 0.80-1.24) for consumption two to four times per week and 1.07 (0.78-1.47) for consumption five or more times per week, relative to consumption once a week or less; for miso soup, relative risks were 1.03 (0.81-1.31) for consumption two to four times per week and 0.87 (0.68-1.12) for consumption five or more times per week, relative to consumption once a week or less. These results were not materially altered by further adjustments for reproductive variables and were similar in women diagnosed before age 50 and at ages 50 and above. Among 17 other foods and drinks examined only dried fish (decrease in relative risk with increasing consumption) and pickled vegetables (higher relative risk with higher consumption) were significantly related to breast cancer risk; these associations were not prior hypotheses and, because of the large number of comparisons made, they may be due to chance.

Adult↗

Mortality in vegetarians and nonvegetarians: detailed findings from a collaborative analysis of 5 prospective studies.

We combined data from 5 prospective studies to compare the death rates from common diseases of vegetarians with those of nonvegetarians with similar lifestyles. A summary of these results was reported previously; we report here more details of the findings. Data for 76172 men and women were available. Vegetarians were those who did not eat any meat or fish (n = 27808). Death rate ratios at ages 16-89 y were calculated by Poisson regression and all results were adjusted for age, sex, and smoking status. A random-effects model was used to calculate pooled estimates of effect for all studies combined. There were 8330 deaths after a mean of 10.6 y of follow-up. Mortality from ischemic heart disease was 24% lower in vegetarians than in nonvegetarians (death rate ratio: 0.76; 95% CI: 0.62, 0.94; P<0.01). The lower mortality from ischemic heart disease among vegetarians was greater at younger ages and was restricted to those who had followed their current diet for >5 y. Further categorization of diets showed that, in comparison with regular meat eaters, mortality from ischemic heart disease was 20% lower in occasional meat eaters, 34% lower in people who ate fish but not meat, 34% lower in lactoovovegetarians, and 26% lower in vegans. There were no significant differences between vegetarians and nonvegetarians in mortality from cerebrovascular disease, stomach cancer, colorectal cancer, lung cancer, breast cancer, prostate cancer, or all other causes combined.

Adolescent↗