Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI breast and prostate cancer cohort consortium.

There is extensive evidence that increases in blood and tissue concentrations of steroid hormones and of insulin-like growth factor I (IGF-I) are associated with breast cancer risk. However, studies of common variation in genes involved in steroid hormone and IGF-I metabolism have yet to provide convincing evidence that such variants predict breast cancer risk. The Breast and Prostate Cancer Cohort Consortium (BPC3) is a collaboration of large US and European cohorts. We genotyped 1416 tagging single nucleotide polymorphisms (SNPs) in 37 steroid hormone metabolism genes and 24 IGF-I pathway genes in 6292 cases of breast cancer and 8135 controls, mostly Caucasian, postmenopausal women from the BPC3. We also imputed 3921 additional SNPs in the regions of interest. None of the SNPs tested was significantly associated with breast cancer risk, after correction for multiple comparisons. The results remained null when cases and controls were stratified by age at diagnosis/recruitment, advanced or nonadvanced disease, body mass index, with or without in situ cases; or restricted to Caucasians. Among 770 estrogen receptor-negative cases, an SNP located 3' of growth hormone receptor (GHR) was marginally associated with increased risk after correction for multiple testing (P(trend) = 1.5 × 10(-4)). We found no significant overall associations between breast cancer and common germline variation in 61 genes involved in steroid hormone and IGF-I metabolism in this large, comprehensive study. Although previous studies have shown that variations in these genes can influence endogenous hormone levels, the magnitude of the effect of single SNPs does not appear to be sufficient to alter breast cancer risk.

American Cancer Society perspectives on environmental factors and cancer.

Cancer prevention is central to the mission of the American Cancer Society (ACS). The ACS's prevention activities take many forms, but are primarily focused on modifiable risk factors that have been demonstrated to have the largest impact on cancer risk in the general population (with particular emphasis on tobacco use because of its large impact on cancer), and well-proven policy and program interventions. The ACS addresses nutrition, physical inactivity and obesity, alcohol consumption, excessive sun exposure, prevention of certain chronic infections, and selected other environmental factors through a variety of venues, including consensus guidelines (eg, nutrition and physical activity, human papillomavirus vaccination) and developing educational materials for health care providers and the general public. In contrast to the broad definition of environmental factors used by the ACS and most other public health agencies, some members of the general public associate the term "environmental" only with toxic air and water pollutants and other, predominantly manmade, hazards that people encounter, often involuntarily, in their daily life. This article will provide an overview of the ACS's approach to the prevention of cancer associated with such toxic pollutants in the context of its mission and priorities with respect to cancer prevention.

Alcohol consumption not associated with lung cancer mortality in lifelong nonsmokers.

Although alcohol consumption is associated with increased lung cancer risk in some studies, this relationship is difficult to interpret because of potential confounding by smoking. We measured lung cancer death rates in relation to self-reported alcohol consumption among 223,216 adults who reported no history of regular smoking when enrolled in a large prospective mortality study begun by the American Cancer Society in 1982. Participants were at least 30 years of age when enrolled and, consequently, were considered unlikely to initiate smoking during follow-up. During 24 years of follow-up, we identified 1,058 deaths from lung cancer. Cox proportional hazards analyses were conducted, adjusting for age, education, occupation, and race. No association between lung cancer mortality and any level of alcohol consumption was seen in men or women. Even among those who consumed four or more alcoholic drinks per day, the risk did not differ from those who abstained from alcohol [hazard ratios 0.97 (95% confidence interval, 0.76-1.22) and 0.69 (0.41-1.16) for men and women, respectively]. Due to the large population of lifelong nonsmokers in our cohort and the long period of follow-up, these findings provide substantial evidence against the hypothesis that alcohol consumption independently increases lung cancer risk.

Occupational exposure to metribuzin and the incidence of cancer in the Agricultural Health Study.

PURPOSE: Little is known about the potential carcinogenicity of the triazinone herbicide metribuzin. We evaluated the association between metribuzin use and cancer risk in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. METHODS: Applicators (N=23,072) provided information on metribuzin use on a self-administered questionnaire at enrollment (1993-1997). Among metribuzin users (n=8,504), there were 554 incident cancer cases. We used multivariable Poisson regression to evaluate potential associations between metribuzin use and cancer incidence by using two quantitative exposure metrics, lifetime days and intensity-weighted lifetime days. RESULTS: Using intensity-weighted lifetime days, the rate ratio (RR) and 95% confidence interval (CI) for the highest exposed tertile for lymphohematopoietic malignancies were 2.09 (95% CI: 0.99-4.29), p trend=0.02 and 2.42 (95% CI: 0.82-7.19), p trend=0.08 for leukemia. For non-Hodgkin lymphoma, the RR was 2.64 (95% CI: 0.76-9.11), p trend=0.13 for lifetime days and 2.52 (95% CI: 0.66-9.59), p trend=0.13 for intensity-weighted lifetime days. Patterns of association were similar for both exposure metrics, but associations were generally weaker than for intensity-weighted days. CONCLUSIONS: The results from this study suggest a potential association between metribuzin use and certain lymphohematopoietic malignancies; however, having not been observed previously, caution should be used in interpretation.

Recent trends in Black-White disparities in cancer mortality.

Despite decreases in overall cancer death rates across all racial and ethnic groups since the early 1990s, racial disparities in cancer mortality persist. We examined temporal trends in Black-White disparities in cancer mortality from all sites combined, smoking-related cancers (lung and a group including oral cavity, pharynx, larynx, esophagus, pancreas, bladder, and kidney), and sites affected, or potentially affected by screening and treatment (breast, prostate, colon/rectum). Death rates, rate differences, and rate ratios comparing Blacks to Whites from 1975 through 2004 were based on mortality data from the National Center for Health Statistics. The Black-White disparity in overall cancer death rates narrowed from the early 1990s through 2004, especially in men. This reduction was driven predominantly by more rapid decreases in mortality from tobacco-related cancers in Black men than White men. In contrast, racial disparities in mortality from cancers potentially affected by screening and treatment increased over most of the interval since 1975. Coordinated efforts to improve early detection and treatment for all segments of the population are essential to eliminate racial disparities in cancer mortality.