Carcinoma of the lung is the most common cause of cancer death worldwide. The estimated 5-year survival ranges from 6 -16%, depending on the cell type. The best opportunity for improving survival of lung cancer patients is through early detection, when curative surgical resection is possible. Although the subjects at increased risk for developing carcinoma of the lung (long-term smokers) can be identified, only 10 -20% of this group will ultimately develop the disease. Screening tests of long-term smokers employed to date (radiography and sputum cytology) have not been successful in reducing lung cancer mortality. The application of molecular markers specific for lung cancer offers new possibilities for early detection. Hypermethylation of CpG islands in the promoter regions of genes is a common phenomenon in lung cancer, as demonstrated by the analysis of the methylation status of over 40 genes from lung cancer tumors, cell lines, patient sputum and/ or serum. Determination of the methylation patterns of multiple genes to obtain complex DNA methylation signatures promises to provide a highly sensitive and specific tool for lung cancer diagnosis. When combined with the development of non-invasive methods to detect such signatures, this may provide a viable method to screen subjects at risk for lung cancer.

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We examined effects of obesity and lifetime exercise patterns on postmenopausal breast cancer risk according to family history in a large population-based case control study conducted in Los Angeles County, California, because we hypothesized that both factors would affect risk through similar mechanistic pathways, and that their effects would be stronger among women with a family history. We studied 1,883 postmenopausal breast cancer case subjects and 1,628 postmenopausal control subjects ranging in age from 55-72 years. Cases were diagnosed with incident breast cancer in the late 1980s and 1990s. Controls were individually matched to case subjects on age, ethnic origin and neighborhood. In-person interviews determined known breast cancer risk factors including: height, weight, lifetime exercise, and family history of breast and other cancers. Breast cancer risk was raised among women who had at least 1 first-degree relative with breast cancer (odds ratio [OR] ‫؍‬ 1.68; 95% confidence interval [CI] ‫؍‬ 1.36 -2.08). Risk increased with increasing levels of body-mass index (wt-kg/ht-m 2 ) (p-trend ‫؍‬ 0.005). Breast cancer risk was reduced among women who maintained, on average, 17.6 metabolic equivalent of energy expenditure (MET)-hr of activity/week from menarche onward (OR ‫؍‬ 0.66; 95% CI ‫؍‬ 0.48 -0.90). Body-mass index, adjusted for lifetime exercise, was strongly associated with breast cancer risk among women with a positive family history of breast cancer (p-trend < 0.0001), but only weakly associated among women with no family history (p-trend ‫؍‬ 0.08; homogeneity of trends p ‫؍‬ 0.0005). In contrast, the risk reduction associated with exercise activity, adjusting for body-mass index, was limited to women without a family history of breast cancer (p-trend ‫؍‬ 0.001; homogeneity of trends p ‫؍‬ 0.005). Body-mass index and exercise activity, both modifiable risk factors for breast cancer, seem to have differential effects depending on a woman's family history of breast cancer, and may impact risk through different biological mechanisms.