Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: Reanalysis of eighteen prospective studies.

Epidemiological studies have examined breast cancer risk in relation to sex hormone concentrations measured by different methods: "extraction" immunoassays (with prior purification by organic solvent extraction, with or without column chromatography), "direct" immunoassays (no prior extraction or column chromatography), and more recently with mass spectrometry-based assays. We describe the associations of estradiol, estrone and testosterone with both body mass index and breast cancer risk in postmenopausal women according to assay method, using data from a collaborative pooled analysis of 18 prospective studies. In general, hormone concentrations were highest in studies that used direct assays and lowest in studies that used mass spectrometry-based assays. Estradiol and estrone were strongly positively associated with body mass index, regardless of the assay method; testosterone was positively associated with body mass index for direct assays, but less clearly for extraction assays, and there were few data for mass spectrometry assays. The correlations of estradiol with body mass index, estrone and testosterone were lower for direct assays than for extraction and mass spectrometry assays, suggesting that the estimates from the direct assays were less precise. For breast cancer risk, all three hormones were strongly positively associated with risk regardless of assay method (except for testosterone by mass spectrometry where there were few data), with no statistically significant differences in the trends, but differences may emerge as new data accumulate. Future epidemiological and clinical research studies should continue to use the most accurate assays that are feasible within the design characteristics of each study.

Anti-Mullerian hormone and risk of invasive serous ovarian cancer.

PURPOSE: Epithelial ovarian cancers either arise directly from Mullerian-type epithelium or acquire Mullerian characteristics in the course of neoplastic transformation. The anti-Mullerian hormone (AMH) causes regression of Mullerian structures during fetal development in males and has been shown to inhibit the growth of epithelial ovarian cancer. Therefore, we hypothesized that pre-diagnostic serum concentrations of AMH are inversely associated with risk of invasive serous ovarian cancer. METHODS: A case-control study (107 cases, 208 controls) was nested within the population-based Finnish Maternity Cohort (1986-2007). The sample donated during the first trimester of the last pregnancy preceding cancer diagnosis of the case subjects was selected for the study. For each case, two controls, matched on age and date at sampling, as well as parity at sampling and at cancer diagnosis were selected. AMH was measured by a second-generation AMH ELISA. Conditional logistic regression was used to compute odds ratios (OR) and 95 % confidence intervals (CI) for invasive serous ovarian cancer associated with AMH concentrations. RESULTS: Overall AMH concentrations were not associated with risk of invasive serous ovarian cancer (OR 0.93; 95 % CI 0.49-1.77 for top vs. bottom tertile, P trend=0.83). In women older than the median age at sampling (32.7 years), a doubling of AMH was associated with decreased risk (OR 0.69; 95 % CI 0.49-0.96), whereas an increased risk (OR 1.64; 95 % CI 1.06-2.54) was observed in younger women, P homogeneity = 0.002. CONCLUSIONS: In this first prospective investigation, risk of invasive serous ovarian cancer was not associated with pre-diagnostic AMH concentrations overall; however, the association may depend on age at AMH measurement.

Sex hormones and risk of breast cancer in premenopausal women: a collaborative reanalysis of individual participant data from seven prospective studies.

BACKGROUND: Associations between circulating concentrations of oestrogens, progesterone, and androgens with breast cancer and related risk factors in premenopausal women are not well understood. We aimed to characterise these associations with a pooled analysis of data from seven studies. METHODS: Individual participant data for prediagnostic sex hormone and sex hormone-binding globulin (SHBG) concentrations were contributed from seven prospective studies. We restricted analyses to women who were premenopausal and younger than 50 years at blood collection, and to women with breast cancer diagnosed before age 50 years. We estimated odds ratios (ORs) with 95% CIs for breast cancer associated with hormone concentrations by conditional logistic regression in cases and controls matched for age, date of blood collection, and day of cycle, with stratification by study and further adjustment for cycle phase. We examined associations of hormones with risk factors for breast cancer in control women by comparing geometric mean hormone concentrations in categories of these risk factors, adjusted for study, age, phase of menstrual cycle, and body-mass index (BMI). All statistical tests were two-sided. FINDINGS: We included data for up to 767 women with breast cancer and 1699 controls in the risk analyses. Breast cancer risk was associated with a doubling in concentrations of oestradiol (OR 1·19, 95% CI 1·06-1·35), calculated free oestradiol (1·17, 1·03-1·33), oestrone (1·27, 1·05-1·54), androstenedione (1·30, 1·10-1·55), dehydroepiandrosterone sulphate (1·17, 1·04-1·32), testosterone (1·18, 1·03-1·35), and calculated free testosterone (1·08, 0·97-1·21). Breast cancer risk was not associated with luteal phase progesterone (doubling in concentration OR 1·00, 95% CI 0·92-1·09), and adjustment for other factors had little effect on any of these ORs. Cross-sectional analyses in control women showed several associations of sex hormones with breast cancer risk factors. INTERPRETATION: Circulating oestrogens and androgens are positively associated with the risk for breast cancer in premenopausal women.

Moderate alcohol consumption and 24-hour urinary levels of melatonin in postmenopausal women.

CONTEXT: Low overnight urinary melatonin metabolite concentrations have been associated with increased risk for breast cancer among postmenopausal women. The Postmenopausal Women's Alcohol Study was a controlled feeding study to test the effects of low to moderate alcohol intake on potential risk factors for breast cancer including serum and urinary levels of hormones and other biomarkers. Previously, we observed significant increases in concentrations of serum estrone sulfate and dehydroepiandrosterone sulfate in participants after consumption of 15 or 30 g (one or two drinks) of alcohol per day. OBJECTIVE: In the present analysis, we evaluated the relationship of alcohol consumption with 24-h urinary 6-sulfatoxymelatonin (6-SMT) concentration (micrograms per 24 h). DESIGN AND PARTICIPANTS: Healthy postmenopausal women (n = 51) consumed a controlled diet plus each of three treatments (a nonalcoholic placebo beverage or 15 or 30 g alcohol/d) during three 8-wk periods in random order under conditions of weight maintenance. MEASURES: 6-SMT was measured in 24-h urine samples that were collected at entry into the study (baseline) and at the midpoint (4 wk) and end (8 wk) of each of the three diet periods. RESULTS: Concentration of 6-SMT was not significantly modified by the alcohol treatment after adjustment for body mass index, hours of sleep, daylight hours, and baseline level of 6-SMT. CONCLUSIONS: These results suggest that low to moderate daily alcohol consumption does not significantly affect 24-h urinary levels of melatonin among healthy postmenopausal women.

Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies.

BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.

No association between alcohol supplementation and autoantibodies to DNA damage in postmenopausal women in a controlled feeding study.

Alcohol consumption is linked to increased breast cancer risk. Since oestrogens increase breast cancer risk, possibly through oxidative damage, and we have shown that alcohol consumption increases serum oestrogens, we tested whether moderate alcohol supplementation increased oxidative DNA damage among healthy postmenopausal women not on hormone replacement therapy in a randomized controlled crossover study. We used serum 5-hydroxymethyl-2-deoxyuridine (5-HMdU) autoantibodies (aAbs) as a marker of oxidative DNA damage. The results showed no evidence for increased or decreased levels of oxidative DNA damage among women who consumed 15 g or 30 g alcohol per day for 8 weeks compared with women in the 0 g alcohol group. We conclude that among healthy women, it is possible that an 8-week trial of moderate alcohol supplementation might be too short to make enough 5-HMdU aAbs to compare differences by alcohol dose. In future studies, a panel of biomarkers for DNA damage should be used.

Moderate alcohol consumption and levels of antioxidant vitamins and isoprostanes in postmenopausal women.

BACKGROUND: Although alcohol intake has been positively associated with breast cancer risk in epidemiologic studies, the mechanisms mediating this association are speculative. OBJECTIVE: The Postmenopausal Women's Alcohol Study was designed to explore the effects of moderate alcohol consumption on potential risk factors for breast cancer. In the present analysis, we evaluated the relationship of alcohol consumption with antioxidant nutrients and a biomarker of oxidative stress. DESIGN: Participants (n=53) consumed a controlled diet plus each of three treatments (15 or 30 g alcohol/day or a no-alcohol placebo beverage), during three 8-week periods in random order. We measured the antioxidants, vitamin E (alpha (alpha)- and gamma (gamma)-tocopherols), selenium, and vitamin C in fasting blood samples which were collected at the end of diet periods, treated and frozen for assay at the end of the study. We also measured 15-F(2t)-IsoP isoprostane, produced by lipid peroxidation, which serves as an indicator of oxidative stress and may serve as a biomarker for conditions favorable to carcinogenesis. RESULTS: After adjusting for BMI (all models) and total serum cholesterol (tocopherol and isoprostane models) we observed a significant 4.6% decrease (P=0.02) in alpha-tocopherol and a marginally significant 4.9% increase (P=0.07) in isoprostane levels when women consumed 30 g alcohol/day (P=0.06 and 0.05 for overall effect of alcohol on alpha-tocopherol and isoprostanes, respectively). The other antioxidants were not significantly modified by the alcohol treatment. CONCLUSIONS: These results suggest that moderate alcohol consumption increases some biomarkers of oxidative stress in postmenopausal women.

Effects of moderate alcohol consumption on folate and vitamin B(12) status in postmenopausal women.

BACKGROUND: Although alcohol intake has been positively associated with breast cancer risk in epidemiologic studies, a causal relationship has not been established, and the mechanisms mediating this association are speculative. Alcohol may act through altered status of folate and vitamin B(12), two vitamins required for DNA methylation and nucleotide synthesis, and thus cell integrity. Although the effects of heavy alcohol intake on folate and vitamin B(12) status have been well-documented, few studies have addressed the effects of moderate alcohol intake in a controlled setting. OBJECTIVE: The objective of this study was to determine the effects of moderate alcohol intake on folate and vitamin B(12) status in healthy, well-nourished, postmenopausal women. DESIGN: The study design was a randomized, diet-controlled crossover intervention. Postmenopausal women (n=53) received three 8-week alcohol treatments in random order: 0, 15, and 30 g/day. Treatment periods were preceded by 2-5-week washout periods. Blood collected at baseline and week 8 of each treatment period was analyzed for serum folate, vitamin B(12), homocysteine (HCY), and methylmalonic acid (MMA) concentrations. RESULTS: After adjusting for body mass index (BMI), a significant 5% decrease was observed in mean serum vitamin B(12) concentrations from 0 to 30 g of alcohol/day (461.45+/-30.26 vs 440.25+/-30.24 pg/ml; P=0.03). Mean serum HCY concentrations tended to increase by 3% from 0 to 30 g of alcohol/day (9.44+/-0.37 vs 9.73+/-0.37 micromol/l; P=0.05). Alcohol intake had no significant effects on serum folate or MMA concentrations. CONCLUSIONS: Among healthy, well-nourished, postmenopausal women, moderate alcohol intake may diminish vitamin B(12) status.

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

Serum hormones and the alcohol-breast cancer association in postmenopausal women.

BACKGROUND: Alcohol ingestion is associated with an increased risk of breast cancer in most epidemiologic studies. Results, however, are heterogeneous at lower levels of alcohol intake, and a biologic mechanism for the association has not been clearly identified. To determine whether alcohol consumption by postmenopausal women elevates serum levels of hormones associated with an increased risk of breast cancer, we performed a controlled feeding study. METHODS: Participants were 51 healthy postmenopausal women not using hormone replacement therapy. Each participant rotated through three 8-week dietary periods in which she consumed 15 or 30 g of alcohol per day or an alcohol-free placebo beverage. The order of assignment to the three alcohol levels was random. During the dietary periods, all food and beverages were supplied by the study, and energy intake was adjusted to keep body weight constant. Levels of estradiol, estrone, estrone sulfate, testosterone, androstenedione, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and androstenediol were measured by radioimmunoassays in serum collected at the end of each dietary period. All statistical tests are two-sided. RESULTS: When women consumed 15 or 30 g of alcohol per day, respectively, estrone sulfate concentrations increased by 7.5% (95% confidence interval [CI] = -0.3% to 15.9%; P =.06) and 10.7% (95% CI = 2.7% to 19.3%; P =.009) and DHEAS concentrations increased by 5.1% (95% CI = 1.4% to 9.0%; P =.008) and 7.5% (95% CI = 3.7% to 11.5%; P<.001) relative to levels when women consumed placebo. None of the other hormones measured changed statistically significantly when women consumed alcohol. CONCLUSIONS: Results suggest a possible mechanism by which consumption of one or two alcoholic drinks per day by postmenopausal women could increase their risk of breast cancer.

Sources of elevated serum androgens in postmenopausal women who develop breast cancer.

Postmenopausal women with elevated serum androgens are at an increased risk of breast cancer. High dehydroepiandrosterone sulfate concentrations in these women suggest increased adrenal secretion. Both the adrenals and ovaries could contribute to elevated concentrations of androstenedione (Delta4A). 11beta-Hydroxyandrostenedione (11betaOHA) is elevated, and the Delta4A:11betaOHA ratio is depressed when the adrenals are the primary source of elevated Delta4A in women. Conversely, Delta4A:11betaOHA is elevated when the ovaries are the primary source. We prospectively evaluated associations of serum 11betaOHA and Delta4A:11betaOHA with breast cancer in the Columbia, Missouri Serum Bank to identify the source of elevated Delta4A related to risk. Fifty-three postmenopausal women who were not taking estrogens when they donated blood and were diagnosed with breast cancer up to 10 years later (median, 2.9 years) served as cases. Two controls, who were also postmenopausal and not taking estrogens, were matched to each case on age, date, and time of blood collection. Serum Delta4A concentration was significantly (trend P = 0.02) positively associated with breast cancer risk. Adjusted risk ratios for women in the lowest to highest tertiles were 1.0, 1.6, and 2.4 [95% confidence interval (CI), 0.9-6.5]. However, neither 11betaOHA concentration nor Delta4A:11betaOHA was related to risk. Comparable risk ratios were 1.0, 1.2, and 1.4 (95% CI, 0.5-3.6) for 11betaOHA and 1.0, 1.2, and 1.2 (95% CI, 0.4-3.5) for Delta4A:11betaOHA. Our results suggest that neither the ovaries nor adrenals are the predominant source of elevated serum Delta4A in postmenopausal women who develop breast cancer, but rather both may contribute.

Covariate measurement error adjustment for matched case-control studies.

We propose a conditional scores procedure for obtaining bias-corrected estimates of log odds ratios from matched case-control data in which one or more covariates are subject to measurement error. The approach involves conditioning on sufficient statistics for the unobservable true covariates that are treated as fixed unknown parameters. For the case of Gaussian nondifferential measurement error, we derive a set of unbiased score equations that can then be solved to estimate the log odds ratio parameters of interest. The procedure successfully removes the bias in naive estimates, and standard error estimates are obtained by resampling methods. We present an example of the procedure applied to data from a matched case-control study of prostate cancer and serum hormone levels, and we compare its performance to that of regression calibration procedures.

Long-term safety and efficacy of a cholesterol-lowering diet in children with elevated low-density lipoprotein cholesterol: seven-year results of the Dietary Intervention Study in Children (DISC).

OBJECTIVE: Diets reduced in fat and cholesterol are recommended for children over 2 years of age, yet long-term safety and efficacy are unknown. This study tests the long-term efficacy and safety of a cholesterol-lowering dietary intervention in children. METHODS: Six hundred sixty-three children 8 to 10 years of age with elevated low-density lipoprotein cholesterol (LDL-C) were randomized to a dietary intervention or usual care group, with a mean of 7.4 years' follow-up. The dietary behavioral intervention promoted adherence to a diet with 28% of energy from total fat, <8% from saturated fat, up to 9% from polyunsaturated fat, and <75 mg/1000 kcal cholesterol per day. Serum LDL-C, height, and serum ferritin were primary efficacy and safety outcomes. RESULTS: Reductions in dietary total fat, saturated fat, and cholesterol were greater in the intervention than in the usual care group throughout the intervention period. At 1 year, 3 years, and at the last visit, the intervention compared with the usual care group had 4.8 mg/dL (.13 mmol/L), 3.3 mg/dL (.09 mmol/L), and 2.0 mg/dL (.05 mmol/L) lower LDL-C, respectively. There were no differences at any data collection point in height or serum ferritin or any differences in an adverse direction in red blood cell folate, serum retinol and zinc, sexual maturation, or body mass index. CONCLUSION: Dietary fat modification can be achieved and safely sustained in actively growing children with elevated LDL-C, and elevated LDL-C levels can be improved significantly up to 3 years. Changes in the usual care group's diet suggest that pediatric practices and societal and environmental forces are having positive public health effects on dietary behavior during adolescence.

Bone mass and the risk of colon cancer among postmenopausal women: the Framingham study.

Although postmenopausal estrogen use has been associated with a lower risk of colon cancer in women, some studies do not confirm such findings. No known study has examined the effect of cumulative estrogen exposure on colon cancer risk. Bone mass has been proposed as a marker of cumulative exposure to endogenous and exogenous estrogens. By using data on 1,394 Massachusetts women in the Framingham Study who underwent hand radiography in 1967-1970, the authors examined the association between bone mass (from relative areas of the second metacarpal) and colon cancer incidence. Over 27 years of follow-up, 44 incident colon cancer cases occurred. Colon cancer incidence decreased from 2.19 per 1,000 person-years among the women in the lowest age-specific tertile of bone mass to 1.59 and 1.08 among women in the middle and the highest tertiles, respectively. After adjustment for age and other potential confounding factors, the rate ratios of colon cancer were 1.0, 0.7 (95% confidence interval: 0.3, 1.3), and 0.4 (95% confidence interval: 0.2, 0.9) from the lowest to the highest tertile (p for trend = 0.033). No association was found between bone mass and rectal cancer. The findings suggest that women with higher bone mass, perhaps reflecting greater cumulative estrogen exposure, have a decreased risk of colon cancer.

Effects of long-term alpha-tocopherol supplementation on serum hormones in older men.

BACKGROUND: alpha-tocopherol supplementation significantly reduced risk of prostate cancer in the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study. Sex hormones are thought to be involved in the etiology of prostate cancer. We examined whether long-term supplementation with alpha-tocopherol modified serum hormone levels. METHODS: Men who were cancer-free consumed > or = 90% of the study capsules, and who had both baseline and follow-up blood available, were eligible for the study. One hundred men who received alpha-tocopherol were matched on age, study center, and length of time between blood draws to 100 men who received a placebo. Multivariate linear regression models which allowed for a separate intercept for each matched pair were used to evaluate the effect of alpha-tocopherol supplementation on follow-up hormone concentrations. RESULTS: Compared to men who received a placebo, we found significantly lower serum androstenedione (P = 0.04) and testosterone (P = 0.04) concentrations among men who received alpha-tocopherol, after controlling for baseline hormone level, follow-up serum cholesterol concentration, body mass index, smoking, and fasting time. Geometric mean (95% confidence interval; CI) androstenedione concentration among men who received alpha-tocopherol was 145 ng/dl (CI, 137-153) after adjusting for covariates, compared to 158 ng/dl (CI, 148-167) among men who received a placebo. Mean testosterone concentrations for men who received alpha-tocopherol and placebo were 539 (CI, 517-562) and 573 (CI, 549-598) ng/dl, respectively. CONCLUSIONS: These results suggest that long-term alpha-tocopherol supplementation decreases serum androgen concentrations, and could have been one of the factors contributing to the observed reduction in incidence and mortality of prostate cancer in the alpha-tocopherol treatment group of the ATBC Study.

Parental age at child's birth and son's risk of prostate cancer. The Framingham Study.

The authors examined the relation of parental age at birth to the risk of prostate cancer among sons with the use of data from the Framingham Study. During 42 years of follow-up (1949-1993), 141 prostate cancer cases occurred in 2,164 men. All but six cases were confirmed by histologic report. The incidence rate of prostate cancer increased from 1.70 per 1,000 person-years among sons in the lowest quartile of paternal age (<27 years), to 2.00, 2.32, and 2.74 among those of each increased paternal age category (27-<32, 32-<38, and > or =38 years), respectively. After adjustment for age and other covariates, men in the second, third, and oldest quartiles of paternal age had 1.2, 1.3, and 1.7 times increased risk of prostate cancer compared with men in the youngest quartile (p for trend = 0.049). Further adjustment for maternal age did not change the relation materially. The association of older paternal age with risk of early-onset prostate cancer (<65 years) appeared stronger than that with late-onset disease (265 years). No increased risk of prostate cancer was observed among subjects in the older maternal age category. The effect of increased paternal age on prostate cancer risk may operate through increased germ cell mutation rate or by mechanisms not yet defined.

Serum organochlorine pesticides and PCBs and breast cancer risk: results from a prospective analysis (USA).

OBJECTIVE: To prospectively evaluate relationships of organochlorine pesticides and polychlorinated biphenyls (PCBs) with breast cancer, we conducted a case-control study nested in a cohort using the Columbia, Missouri Breast Cancer Serum Bank. METHODS: Women donated blood in 1977-87, and during up to 9.5 years follow-up, 105 donors who met the inclusion criteria for the current study were diagnosed with breast cancer. For each case, two controls matched on age and date of blood collection were selected. Five DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] analogs, 13 other organochlorine pesticides, and 27 PCBs were measured in serum. RESULTS: Women in the upper three quartiles of hexachlorobenzene were at twice the risk of breast cancer compared to those in the lowest quartile. However, there was no evidence for a dose-response relationship, and the association was limited to women whose blood was collected close to the time of diagnosis. Women with higher serum levels of other organochlorine pesticides and PCBs showed no increased risk of breast cancer overall, although positive associations were suggested for PCB-118 and PCB-138 when blood was collected close to the time of diagnosis. CONCLUSIONS: Results of this study do not support a role for organochlorine pesticides and PCBs in breast cancer etiology.

Alcohol consumption and risk of breast cancer: the Framingham Study revisited.

Although many studies report that moderate-to-heavy alcohol intake increases breast cancer risk, the effect of light alcohol consumption remains controversial, and a consistent pattern of association with different types of alcoholic beverages is not evident. The authors examined the relation of average alcohol consumption and of different beverages to the risk of breast cancer in the Framingham Study (Framingham, Massachusetts). Of 2,764 women followed more than 40 years in the Original Cohort from 1948 to 1993 and 2,284 followed up to 24 years in the Offspring Cohort from 1971 to 1993, 221 and 66 incident breast cancer cases occurred, respectively. Breast cancer incidence decreased from 3.60 per 1,000 person-years to 2.47, 2.30, and 2.33 in increasing categories of average alcohol consumption (none, < 5.0, 5.0-< 15.0, and > or = 15.0 g/day) among the Original Cohort and from 3.07 to 1.26, 1.24, and 2.22, respectively, among the Offspring Cohort. With the two cohorts combined, multivariate-adjusted rate ratios of breast cancer in each increased category of alcohol consumption were 1.0 (nondrinkers), 0.8 (95% confidence interval (CI) 0.6-1.1), 0.7 (95% CI 0.5-1.1), and 0.7 (95% CI 0.5-1.1), respectively. Breast cancer was not associated with wine, beer, or spirits consumption when assessed separately. The findings suggest that the light consumption of alcohol or any type of alcoholic beverage is not associated with increased breast cancer risk.

Association between serum alpha-tocopherol and serum androgens and estrogens in older men.

There is evidence supporting a role for sex hormones in the etiology of prostate cancer. Supplementation with alpha-tocopherol reduced prostate cancer in the alpha-Tocopherol, beta-Carotene Prevention Study (ATBC Study). The objective of this study was to assess the relation of baseline levels of serum alpha-tocopherol and serum sex hormones in older men. A cross-sectional analysis of serum alpha-tocopherol and sex hormone concentrations was conducted within a subset of the ATBC Study. Serum was collected in the morning after an overnight fast at baseline from 204 men ages 50-69 years participating in the ATBC Study and free of prostate cancer. Hormones were measured by radioimmunoassay, and alpha-tocopherol was measured by high-performance liquid chromatography by standard procedures. Multivariate linear regression was used to evaluate the association of serum alpha-tocopherol with nine androgens and estrogens after controlling for age, body mass index, hormone assay batch, and serum cholesterol. Serum alpha-tocopherol was significantly inversely associated with serum androstenedione, testosterone, sex hormone-binding globulin, and estrone. The difference in hormone concentration per milligram of alpha-tocopherol was 1.8-2.6% for these four hormones. These results indicated that alpha-tocopherol is related to concentrations of several sex hormones in older men and may have implications for the observed protective effect of supplemental vitamin E in relation to prostate cancer in the ATBC Study.