Cigarette smoking and postmenopausal breast cancer risk in a prospective cohort.

BACKGROUND: The relationship between cigarette smoking and breast cancer risk has been inconsistent, potentially due to modification by other factors or confounding. METHODS: We examined smoking and breast cancer risk in a prospective cohort of 186 150 female AARP (formerly American Association of Retired Persons) members, ages 50-71 years, who joined the study in 1995-96 by responding to a questionnaire. Through 2006, 7481 breast cancers were diagnosed. Multivariable-adjusted hazard ratios (HRs) were estimated, overall and stratified by breast cancer risk factors, using Cox proportional hazards regression. Multiplicative interactions were evaluated using the likelihood ratio test. RESULTS: Increased breast cancer risk was associated with current (HR 1.19, 95% confidence interval (CI) 1.10-1.28) and former (HR 1.07, CI 1.01-1.13) smoking. The current smoking association was stronger among women without (HR 1.24, CI 1.15-1.35) as compared to those with a family history of breast cancer (HR 0.94, CI 0.78-1.13) (P-interaction=0.03). The current smoking association was also stronger among those with later (≥ 15 years: HR 1.52, CI 1.20-1.94) as compared with earlier (≥12 years: HR 1.14, CI 1.03-1.27; 13-14 years: HR 1.18, CI 1.05-1.32) ages at menarche (P-interaction=0.03). CONCLUSIONS: Risk was elevated in smokers, particularly in those without a family history or late menarche. Research into smoking's effects on the genome and breast development may clarify these relationships.

Ovarian cancer and menopausal hormone therapy in the NIH-AARP diet and health study.

BACKGROUND: Women using unopposed estrogens during menopause are at increased risk of ovarian cancer. It is uncertain whether oestrogen plus progestin therapy exerts similar effects. METHODS: We evaluated menopausal hormone use and incident ovarian cancer (n=426) in 92601 post-menopausal women enrolled in the National Institutes of Health-AARP (NIH-AARP) Diet and Health Study. Participants were administered questionnaires in 1996-1997 and followed through 2006. Hazard rate ratios (RR) and 95% confidence intervals (CIs) were estimated using Cox regression. RESULTS: Increased risks were associated with long duration (10+ years) use of unopposed oestrogen (RR 2.15, 95% CI: 1.30-3.57 among women with a hysterectomy) and oestrogen plus progestin (RR 1.68, 95% CI: 1.13-2.49 among women with intact uteri) therapy. Similar risks were associated with progestins that were used sequentially (<15 days progestin per month) (RR 1.60, 95% CI: 1.10-2.33) or continuously (>25 days progestin per month) (RR 1.43, 95% CI: 1.032-2.01; P-value for heterogeneity=0.63). CONCLUSION: Our findings suggest that long duration use of both unopposed estrogens and oestrogen plus progestins are associated with increased risks of ovarian cancer, and that risk associated with oestrogen plus progestin use does not vary by regimen (sequential or continuous).

Variants in circadian genes and prostate cancer risk: a population-based study in China.

Circadian genes influence a variety of biological processes that are important in prostate tumorigenesis including metabolism. To determine if variants in circadian genes alter prostate cancer risk, we genotyped five variants in five circadian genes in a population-based case-control study conducted in China (187 cases and 242 controls). These variants included CRY2 rs1401417:G>C, CSNK1E rs1005473:A>C, NPAS2 rs2305160:G>A, PER1 rs2585405:G>C and PER3 54-bp repeat length variant. Men with the cryptochrome 2 (CRY2)-variant C allele had a significant 1.7-fold increased prostate cancer risk (95% confidence interval (CI), 1.1-2.7) relative to those with the GG genotype. This risk increased to 4.1-fold (95% CI, 2.2-8.0) in men who also had greater insulin resistance (IR) as compared to men with the GG genotype and less IR. In contrast, among men with less IR, the NPAS2-variant A allele was associated with decreased prostate cancer risk (odds ratio=0.5, 95% CI, 0.3-1.0) as compared to the GG genotype. Our findings, although in need of confirmation, suggest that variations in circadian genes may alter prostate cancer risk and some biological processes may modify this effect.

A prospective study of postmenopausal hormone use and ovarian cancer risk.

The relationship between postmenopausal hormone use (PMH) and ovarian cancer risk is unclear, particularly for specific hormone formulations, but recent studies suggest that there is a positive association. We conducted a prospective observational study with 82,905 postmenopausal women, including 389 ovarian cancers, in the Nurses' Health Study from 1976 to 2002. Compared with never users of PMH, both current and past users of > or =5 years had a significantly elevated risk of ovarian cancer (RR=1.41, 95% confidence interval (CI) 1.07-1.86 and relative risk (RR)=1.52, 95% CI 1.01-2.27, respectively). Examined by hormone type in continuous years, use of unopposed estrogen was associated with a significant increase in the risk of epithelial ovarian cancer (P for trend <0.001; RR for 5-year increment of use=1.25, 95% CI 1.12-1.38). Use of estrogen plus progestin (RR for 5-year increment of use=1.04, 95% CI 0.82-1.32) was not significantly associated with ovarian cancer risk. Generally, results were similar for serous tumours (RR for 5-year increment of unopposed estrogen use=1.23, 95% CI 1.07-1.40) and slightly stronger for endometrioid tumours (RR for 5-year increment of unopposed estrogen use=1.53, 95% CI 1.20-1.94). Recency of use was not significantly associated with ovarian cancer risk, but statistical power was limited here.