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Background:Hepatocellular carcinoma (HCC) occurs less commonly among women than men in almost all regions of the world. The disparity in risk is particularly notable prior to menopause suggesting that hormonal exposures during reproductive life may be protective. Exogenous oestrogenic exposures such as oral contraceptives (OCs), however, have been reported to increase risk, suggesting that estrogens may be hepatocarcinogenic. To examine the effects of reproductive factors and exogenous hormones on risk, we conducted a prospective analysis among a large group of US women.Methods:In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, data from 799 500 women in 11 cohorts were pooled and harmonised. Cox proportional hazards regression models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of reproductive factors and exogenous hormones with HCC (n=248).Results:Bilateral oophorectomy was associated with a significantly increased risk of HCC (HR=2.67, 95% CI=1.22-5.85), which did not appear to be related to a shorter duration of exposure to endogenous hormones or to menopausal hormone therapy use. There was no association between OC use and HCC (HR=1.12, 95% CI=0.82-1.55). Nor were there associations with parity, age at first birth, age at natural menopause, or duration of fertility.Conclusions:The current study suggests that bilateral oophorectomy increases the risk of HCC but the explanation for the association is unclear. There was no association between OC use and HCC risk. Examination of endogenous hormone levels in relation to HCC may help to clarify the findings of the current study. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) occurs less commonly among women than men in almost all regions of the world. The disparity in risk is particularly notable prior to menopause suggesting that hormonal exposures during reproductive life may be protective. Exogenous oestrogenic exposures such as oral contraceptives (OCs), however, have been reported to increase risk, suggesting that estrogens may be hepatocarcinogenic. To examine the effects of reproductive factors and exogenous hormones on risk, we conducted a prospective analysis among a large group of US women. Methods: In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, data from 799,500 women in 11 cohorts were pooled and harmonised. Cox proportional hazards regression models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of reproductive factors and exogenous hormones with HCC (n=248). Results: Bilateral oophorectomy was associated with a significantly increased risk of HCC (HR=2.67, 95% CI=1.22-5.85), which did not appear to be related to a shorter duration of exposure to endogenous hormones or to menopausal hormone therapy use. There was no association between OC use and HCC (HR=1.12, 95% CI=0.82-1.55). Nor were there associations with parity, age at first birth, age at natural menopause, or duration of fertility. Conclusions: The current study suggests that bilateral oophorectomy increases the risk of HCC but the explanation for the association is unclear. There was no association between OC use and HCC risk. Examination of endogenous hormone levels in relation to HCC may help to clarify the findings of the current study. [ABSTRACT FROM AUTHOR]

Both endogenous factors (genomic variations) and exogenous factors (environmental exposures, lifestyle) impact the balance of reactive oxygen species (ROS). Variants of the ND3 (rs2853826; G10398A) gene of the mitochondrial genome, manganese superoxide dismutase ( MnSOD; rs4880 Val16Ala) and glutathione peroxidase ( GPX-1; rs1050450 Pro198Leu), are purported to have functional effects on regulation of ROS balance. In this study, we examined associations of breast and prostate cancer risks and survival with these variants, and interactions between rs4880-rs1050450, and alcohol consumption-rs2853826. Nested case-control studies were conducted in the Breast and Prostate Cancer Cohort Consortium (BPC3), consisting of nine cohorts. The analyses included over 10726 post-menopausal breast and 7532 prostate cancer cases with matched controls. Logistic regression models were used to evaluate associations with risk, and proportional hazard models were used for survival outcomes. We did not observe significant interactions between polymorphisms in MnSOD and GPX-1, or between mitochondrial polymorphisms and alcohol intake and risk of either breast (p-interaction of 0.34 and 0.98, respectively) or prostate cancer (p-interaction of 0.49 and 0.50, respectively). We observed a weak inverse association between prostate cancer risk and GPX-1 Leu198Leu carriers (OR 0.87, 95% CI 0.79-0.97, p = 0.01). Overall survival among women with breast cancer was inversely associated with G10398 carriers who consumed alcohol (HR 0.66 95% CI 0.49-0.88). Given the high power in our study, it is unlikely that interactions tested have more than moderate effects on breast or prostate cancer risk. Observed associations need both further epidemiological and biological confirmation. [ABSTRACT FROM AUTHOR]

Background:Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes.Methods:We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28 829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma.Results:Significant risk factors for uterine sarcoma included obesity (body mass index (BMI)30 vs BMI<25 kg m−2 (OR: 1.73, 95% CI: 1.22-2.46), P-trend=0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41-3.83). Older age at menarche was inversely associated with uterine sarcoma risk (15 years vs <11 years (OR: 0.70, 95% CI: 0.34-1.44), P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82-3.26) or MMMTs (OR: 2.25, 95% CI: 1.60-3.15, P-heterogeneity=0.01).Conclusion:In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age- and race-specific incidence rates for uterine sarcoma are needed. [ABSTRACT FROM AUTHOR]

OBJECTIVE:Waist-to-hip ratio (WHR) is strongly associated with prevalent atherosclerosis. We analyzed the associations of baseline serum levels of testosterone (T), estradiol (E2), sex-hormone-binding globulin (SHBG) and dehydroepiandrosterone (DHEA) with WHR in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.SUBJECTS:Baseline data was available for 3144 men and 2038 postmenopausal women, who were non-users of hormone therapy, who were 45-84 years of age, and of White, Chinese, Black or Hispanic racial/ethnic groups. Of these, 2708 men and 1678 women also had longitudinal measurements of WHR measured at the second and/or the third study visits (median follow-up 578 days and 1135 days, respectively).RESULTS:In cross-sectional analyses adjusted for age, race and cardiovascular disease risk factors, T was negatively associated with baseline WHR in men, whereas in both sexes, E2 was positively associated and SHBG was negatively associated with WHR (all P<0.001). In longitudinal analyses, further adjusted for follow-up time and baseline WHR, baseline T was negatively associated with WHR at follow-up (P=0.001) in men, whereas in both sexes, E2 was positively associated (P=0.004) and SHBG was negatively associated with WHR (P<0.001). The longitudinal association of E2, but not T, was independent of SHBG. In cross-sectional or longitudinal analyses, there were no associations between DHEA and WHR in either men or women.CONCLUSION:Sex hormones are associated with WHR at baseline and also during follow-up above and beyond their baseline association. Future research is needed to determine if manipulation of hormones is associated with changes in central obesity. [ABSTRACT FROM AUTHOR]

Objectives:To compare age-associated 8-year changes in total testosterone, calculated bioavailable testosterone and sex hormone binding globulin (SHBG) across five groups of men stratified according to change in body mass index (BMI) (i.e., BMI stable (±0.69 kg/m2), decreased (−0.7 kg/m2), increased minimally (0.7–1.74 kg/m2), increased moderately (1.75–3.19 kg/m2) and increased most (3.20 kg/m2)).Design:Eight-year longitudinal cohort study.Subjects:Four hundred and seventy-four black and 695 white men, aged 24–31 years at the time of the first hormone measurement.Measurements:Aging-related changes in serum SHBG, total testosterone and bioavailable testosterone.Results:SHBG significantly increased with age for men whose BMI decreased, and there were progressively smaller increases for men whose BMI was stable, or whose BMI increased minimally or moderately (range 1.1–0.3 nM per year, P0.03, respectively). There was no age relationship with SHBG among men whose BMI increased most. Total testosterone did not change with age for men whose BMI decreased, was stable or increased minimally, but for men whose BMI increased moderately and most there was a graded decrease in total testosterone with age (β=−0.2 and −0.4 nM per year, respectively, P0.005). However, bioavailable testosterone decreased with age to a similar extent across all groups.Conclusions:These results suggest that changes in BMI during young adulthood modulate age-related changes in SHBG and total testosterone, but not bioavailable testosterone.International Journal of Obesity (2007) 31, 685–691. doi:10.1038/sj.ijo.0803465; published online 12 September 2006 [ABSTRACT FROM AUTHOR]

Objective:To investigate the association between obesity and risk of renal cell carcinoma and to examine whether the association is modified by physical activity.Subjects:A population-based case–control study of 406 patients with renal cell carcinoma and 2434 controls conducted in Iowa.Methods:Information was collected on weight at the ages 20–29, 40–49, and 60–69 years, height, nonoccupational physical activity, diet, and other lifestyle factors. Renal cell carcinoma risk was estimated by odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, total energy intake, and other confounding factors.Results:Height and total energy intake were not associated with risk in either sex. In men, neither physical activity nor level of obesity in any period of life was significantly associated with risk. In women, lower physical activity was associated with higher risk (OR=2.5; 95% CI=1.2–5.2 comparing exercise <1 time/month to >1 time/day). Compared with women in the lowest quartile for BMI, the risks of renal cell carcinoma for women in the highest 10% of BMI in their 20s, 40s, and 60s were 1.4 (CI=0.6–3.1), 1.9 (CI=0.9–4.2), and 2.3 (CI=0.9–6.0), respectively. When analyses were limited to self-respondent data, the corresponding ORs were 2.9 (CI=1.2–7.4), 3.2 (CI=1.3–7.5), and 2.1 (CI=0.7–6.4), respectively. There was little evidence that physical activity modifies the association of BMI with renal cell carcinoma.Conclusion:Nonoccupational physical activity was inversely associated and obesity was positively associated with risk of renal cell carcinoma among women. The risk appeared to be greater for women in the highest 10% of BMI in their 40s. Our finding of little evidence of an interaction between physical activity and BMI requires confirmation.International Journal of Obesity (2006) 30, 940–947. doi:10.1038/sj.ijo.0803231; published online 31 January 2006 [ABSTRACT FROM AUTHOR]

Objective: Findings from epidemiologic studies on the association between diabetes and prostate cancer risk are inconsistent. However, data from at least three studies suggest that the direction and strength of this association differs according to duration of diabetes. To determine the potential effects of early-stage abnormal glucose metabolism on risk, we assessed the relationship of postload glycemia in the absence of self-reported diabetes with risk of prostate cancer mortality.Methods: Data from the Chicago Heart Association Detection Project in Industry were used to examine this relationship. Between 1967 and 1973 some employees of 84 Chicago area organizations underwent a health screening examination. Blood was drawn for measurement of plasma glucose concentration approximately 1 h after a 50-g oral glucose load among 20,433 men. After a mean length of follow-up of 27 years, 176 men died of prostate cancer. Cox regression was used to compute adjusted relative risks (RRs) and 95% confidence intervals (CIs).Results: After controlling for age, body mass index, heart rate, education, and race, the RRs of prostate cancer mortality for postload plasma glucose levels of 6.7-8.8, 8.9-11, and > or = 11.1 mmol/L compared to < or = 6.6 mmol/L were 1.64, 1.37, and 1.64. respectively (p for trend=0.19). The RR (95% CI) associated with a 2.2 mmol/L (1 standard deviation) higher glucose concentration was 1.1 (0.95-1.2).Conclusions: These results provide weak evidence of an association between hyperglycemia and prostate cancer mortality. [ABSTRACT FROM AUTHOR]

Context: Previous studies reported an increased risk of pancreatic cancer among persons with diabetes. Few data exist, however, on the association of postload plasma glucose concentration with pancreatic cancer, which could provide insight into the role of abnormal glucose metabolism in the etiology of pancreatic cancer.Objective: To determine the independent association between postload plasma glucose concentration and risk of pancreatic cancer mortality among persons without self-reported diabetes.Design: Prospective cohort study.Setting and Participants: Employees of 84 Chicago-area organizations, with an average age of 40 years at baseline, were screened from 1963 to 1973 and followed up for an average of 25 years. A total of 96 men and 43 women died of pancreatic cancer among 20,475 men and 15,183 women, respectively.Main Outcome Measures: Relationship of pancreatic cancer mortality with postload plasma glucose levels.Results: Compared with a postload plasma glucose level of 6.6 mmol/L (119 mg/dL) or less and after adjusting for age, race, cigarette smoking, and body mass index, the relative risks (95% confidence intervals) of pancreatic cancer mortality were 1.65 (1.05-2.60) for postload plasma glucose levels between 6.7 (120) and 8.8 (159) mmol/L (mg/dL); 1.60 (0.95-2.70) for levels between 8.9 (160) and 11.0 (199); and 2.15 (1.22-3.80) for levels of 11.1 (200) or more; P for trend=.01. An association appeared to be stronger for men than women. Estimates were only slightly lower after excluding 11 men and 2 women who died of pancreatic cancer during the first 5 years of follow-up. In men only, higher body mass index and serum uric acid concentration also were independently associated with an elevated risk of pancreatic cancer mortality.Conclusion: These results suggest that factors associated with abnormal glucose metabolism may play an important role in the etiology of pancreatic cancer. JAMA. 2000;283:2552-2558 [ABSTRACT FROM AUTHOR]

Context: Long-term, postmenopausal use of hormone replacement therapy (HRT) appears to increase breast cancer risk. Whether the effect of HRT use on risk of breast cancer varies among histological types of invasive carcinoma is unknown.Objective: To determine associations between HRT use and risk of ductal carcinoma in situ (DCIS), invasive carcinoma with favorable histology, and invasive ductal or lobular carcinoma.Design: Prospective cohort study whose participants were followed up continuously for 11 years from January 1986 to December 1996.Setting and Participants: Iowa Women's Health Study, a population-based random sample of postmenopausal women aged 55 to 69 years in 1986. A total of 1520 incident breast cancer cases occurred in the at-risk cohort of 37 105 women.Main Outcome Measures: Multivariate-adjusted relative risk (RR) of tumor-specific breast cancers associated with duration of ever, current, or past HRT use.Results: Duration of ever HRT use was associated with risk of invasive carcinoma with a favorable histology, with an RR of 1.81 (95% confidence interval [CI], 1.07-3.07) for those who used HRT 5 or fewer years vs an RR of 2.65 (95% CI, 1.34-5.23) for those who used HRT for more than 5 years (P for trend = .005) after adjustment for age and other breast cancer risk factors. There was no association between ever HRT use and the incidence of DCIS or invasive ductal or lobular carcinoma. Among current hormone users, after adjusting for age and other breast cancer risk factors, the RRs (95% CIs) of invasive carcinoma with a favorable histology were 4.42 (2.00-9.76) and 2.63 (1.18-5.89) for 5 or fewer years of use and for more than 5 years of use, respectively. Risk of invasive ductal or lobular carcinoma was associated with current use (< or =5 years) of HRT with an RR of 1.38 (95% CI, 1.03-1.85).Conclusions: Exposure to HRT was associated most strongly with an increased risk of invasive breast cancer with a favorable prognosis. These data add important clinical information for assessing the risks and benefits of HRT use. [ABSTRACT FROM AUTHOR]

We investigated the relation of alcohol consumption to risk of non-Hodgkin's lymphoma (NHL) in a cohort of 35 156 Iowa women aged 55-69 years who participated in the Iowa Women's Health Study in 1986. Alcohol consumption at baseline was obtained using a mailed questionnaire. During the 9-year follow-up period, 143 incident cases of NHL were identified. Higher alcohol consumption was significantly associated with a decreased risk of NHL (P-trend = 0.03). Compared to non-drinkers, multivariate-adjusted relative risks (RRs) were decreased for women with intake of < or = 3.4 g day(-1) (RR = 0.78; 95% confidence interval (CI) 0.51-1.21) and > 3.4 g day(-1) (RR = 0.59; 0.36-0.97). The inverse association could not be attributed to one particular type of alcoholic beverage, although red wine (RR = 0.21 for > 2 glasses per month vs non-drinker; 0.05-0.86; P-trend = 0.02) has the most distinct effect. The apparent protective effect was universal regardless of specific NHL grade or Working Formulation subtype, but was most pronounced for nodal NHL (RR = 0.48; 0.26-0.90; P-trend = 0.01) and low-grade NHL (RR = 0.52; 0.21-1.26; P-trend = 0.05). These data suggest that moderate alcohol consumption is inversely associated with the risk of NHL in older women and the amount of alcohol consumed, rather than the type of alcoholic beverages, appears to be the main effect determinant. [ABSTRACT FROM AUTHOR]

Gapstur S M (Division of Epidemiology, University of Minnesota, School of Public Health, Suite 300 1300 South Second Street, Minneapolis, MN 55454-1015, USA), Potter J D and Folsom A R. Alcohol consumption and colon and rectal cancer in postmenopausal women. International Journal of Epidemiology 1994; 23: 50–57. The associations between alcohol and colon and rectal cancers were examined in the Iowa Women's Health Study. In January 1986, 41 837 postmenopausal women, aged 55–69, completed a questionnaire including usual alcohol intake and other information. Through December 1990, 237 incident colon and 75 rectal cancer cases occurred. Mantel-Haenszel age-adjusted relative risks (RR) and 95% confidence intervals (CD for consumers of <4.0 and ≥4.0 g of alcohol per day compared to abstainers were 1.07 (0.617ndash;1.89) and 1.27 (0.72–2.24) {P for trend=0.46) for rectal cancer. Alcohol intake was inversely associated with distal colon cancer (RR for <4.0 and ≥4.0 g of alcohol per day were 0.64 and 0.69 respectively, Pfor trend=0.04), which was specific to wine; however, no association was observed with proximal colon cancer (P for trend=0.94). This is the only report of an inverse association between alcohol and colon cancer in women. Because gut physiology and alcohol metabolism differ between men and women, more research on the association between alcohol and colon cancer in women only, is warranted. [ABSTRACT FROM PUBLISHER]