• Adulthood lifetime physical activity and breast cancer.

      Peplonska, Beata; Lissowska, Jolanta; Hartman, Terryl J.; Szeszenia-Dabrowska, Neonila; Blair, Aaron; Zatonski, Witold; Sherman, Mark E.; Garcia-Closas, Montserrat; Brinton, Louise A. (2008-03)
      BACKGROUND: Epidemiologic studies have shown that breast cancer risk is reduced 30% to 40% in highly physically active compared with inactive women. However, the effects of moderate activities, timing of activities, and intervening effects of other risk factors remain less clear. METHODS: We analyzed data on physical activity patterns in 2176 incident breast cancer cases and 2326 controls in a population-based breast cancer case-control study in Poland conducted in 2000-2003. Using unconditional logistic regression analyses, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) associated with physical activity levels (measured by average metabolic equivalents of energy expenditure hours per week), controlling for potential confounders. RESULTS: Total adult lifetime activity reduced risk of breast cancer, with individuals in the highest quartile having an OR of 0.80 (CI = 0.67-0.96) compared with the lowest quartile. Reduced risks were most consistent for the highest quartiles of moderate-to-vigorous activities: moderate/vigorous recreational activities (OR = 0.74; CI = 0.62-0.89), outdoor activities (0.81; 0.68-0.97), heavy physical work (0.60; 0.42-0.87), and combined high intensity (metabolic equivalent >6.0) activities (0.75; 0.63-0.90). These relations were not modified by body mass index, menopausal status, or family history of breast cancer. Reductions in risk with moderate/vigorous recreational activities were stronger for larger tumors and those with nodal involvement. Women who increased their recreational activity in their 50s had significantly reduced risk, with those in the highest tertile of change being at a 27% lower risk. CONCLUSIONS: Leisure-time moderate-to-vigorous activities reduce breast cancer risk irrespective of underlying host characteristics.
    • Prospective study of urinary excretion of 7-methylguanine and the risk of lung cancer: Effect modification by mu class glutathione-S-transferases.

      Loft, Steffen; Svoboda, Peter; Kasai, Hiroshi; Tjonneland, Anne; Moller, Peter; Sorensen, Mette; Overvad, Kim; Autrup, Herman; Raaschou-Nielsen, Ole (2007-10-01)
      Nitrosamines are mainly mutagenic through methylation of DNA. 7-Methylguanine (m(7)Gua) is a product of base excision repair and spontaneous depurination of such lesions in DNA and a metabolite from RNA. Associations between urinary excretion of m(7)Gua and risk of lung cancer were examined in a population-based cohort of 25,717 men and 27,972 women aged 50-64 years. During 3-7 years follow-up 260 cases with lung cancer were identified and a subcohort of 263 individuals matched on sex, age and smoking duration was selected for comparison. Urine collected at entry was analyzed for m(7)Gua by HPLC. Effect modification by glutathione-S-transferases GSTM1, GSTM3, GSTT1 and GSTP1 was investigated. We found higher excretion of m(7)Gua among current smokers than among former smokers. The IRR (incidence rate ratio) of lung cancer was 1.20 (95% CI: 1.00-1.43) per doubling of m(7)Gua excretion in unadjusted analysis and 1.12 (95% CI: 0.93-1.35) after adjustment for smoking status, intensity and duration at entry. This association was mainly present among current smokers. Comparing the highest with the lowest tertile of m(7)Gua excretion the IRR of lung cancer was 1.75 (95% CI: 1.04-2.95) irrespective of genotype and 2.75 (95% CI: 1.33-5.81) in subjects with GSTM1 null genotype. If not caused by residual confounding by smoking a possible association between m(7)Gua excretion and lung cancer supports the importance of methylation of guanine. The finding of an association between m(7)Gua excretion and lung cancer risk mainly among current smokers and subjects with GSTM1 null genotype supports causality in this respect.