Abstract 675: Interplay between dietary trace metal, energy balance, genes in DNA repair pathway and bladder cancer risk

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL We analyzed the association between dietary trace metals and bladder cancer (BC) risk using data collected in a large on-going case-control study. The study included 932 histologically confirmed BC cases and 1239 healthy controls matched to cases by age (± 5 years), gender and ethnicity. Epidemiologic and dietary data were collected using structured questionnaires via an in-person interview. Dietary intake was reported on the National Cancer Institute- Block 135-item food frequency questionnaire (FFQ). Multivariate unconditional logistic regression was used to estimate odds ratios (ORs) and the 95% confidence intervals (95% CI). We observed increased ORs with decreasing intakes of copper, iron, and manganese. For example, compared to the first quartile (the highest quartile) of copper intake, we observed increased ORs for the second (OR=1.64; 95%CI=1.23-2.17), third (OR=2.14; 95% CI=1.55-2.94), and fourth (OR=2.97; 95% CI=2.01-4.38) quartile, respectively (p trend < 0.001). Similar results were found for intakes of iron and manganese. The association was borderline significant for zinc and there was no association for selenium intake. Interestingly, in stratified analyses, the increased risk associated with low copper and manganese was only present in subjects with high energy intake, with low physical activity and in subjects who were overweight and or obese. For example, the ORs for the lowest quartile copper intake was only significantly increased in overweight subjects (OR=3.42; 95% CI=1.88-6.22), in obese subjects (OR=4.21; 95% CI=2.01-8.79), in subjects with low physical activity (OR=4.72; 95% CI=1.89-11.78), and in subjects with high energy intake (OR=3.88; 95% CI=1.00-14.93). These associations were not present in subjects with normal weight (OR=1.68; 95% CI=0.79-3.61), with high physical activity (OR=0.96; 0.35-2.64) or with low energy intake (OR=1.65; 95% CI=0.39-6.92). When analyzed with genetic variants in DNA repair pathways, compared with subjects in the highest quartile of copper intake and who carried low number of unfavorable genotypes (less than 6), subjects carrying eight or more unfavorable genotypes and whose copper intake was in the lowest quartile were at 7.55-fold increased risk (95% CI=3.94-14.48; P<0.001). Finally, in joint analysis, subjects who had low trace metal intake, carried high number of genetic variants and who were at worst energy balance status (obese, low physical activity and high energy intake) were at the highest increased risk (e.g. more than 8-fold), as compared to subjects with none of these risk factors. This is the first study reporting joint effects of dietary trace metal, energy balance, and genetic variants in DNA repair pathway in BC. Our results strongly support that dietary intakes of trace metal are associated with BC risk and the association may be modified by energy balance status and genetic variants in the DNA repair pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 675. doi:1538-7445.AM2012-675