Factors associated with oxidative stress and cancer risk in the Breast and Prostate Cancer Cohort Consortium

Abstract

Both endogenous factors (genomic variations) and exogenous factors (environmental exposures, lifestyle) impact the balance of reactive oxygen species (ROS). Variants of the ND3 (rs2853826; G10398A) gene of the mitochondrial genome, manganese superoxide dismutase (MnSOD; rs4880 Val16Ala) and glutathione peroxidase (GPX-1; rs1050450 Pro198Leu), are purported to have functional effects on regulation of ROS balance. In this study, we examined associations of breast and prostate cancer risks and survival with these variants, and interactions between rs4880–rs1050450, and alcohol consumption—rs2853826. Nested case-control studies were conducted in the Breast and Prostate Cancer Cohort Consortium (BPC3), consisting of nine cohorts. The analyses included over 10726 post-menopausal breast and 7532 prostate cancer cases with matched controls. Logistic regression models were used to evaluate associations with risk, and proportional hazard models were used for survival outcomes. We did not observe significant interactions between polymorphisms in MnSOD and GPX-1, or between mitochondrial polymorphisms and alcohol intake and risk of either breast (p-interaction of 0.34 and 0.98, respectively) or prostate cancer (p-interaction of 0.49 and 0.50, respectively). We observed a weak inverse association between prostate cancer risk and GPX-1 Leu198Leu carriers (OR 0.87, 95% CI 0.79–0.97, p = 0.01). Overall survival among women with breast cancer was inversely associated with G10398 carriers who consumed alcohol (HR 0.66 95% CI 0.49–0.88). Given the high power in our study, it is unlikely that interactions tested have more than moderate effects on breast or prostate cancer risk. Observed associations need both further epidemiological and biological confirmation.

Keywords::

• MnSOD
• GPX-1
• mitochondria
• alcohol
• breast
• prostate

Acknowledgments

The authors thank the CPS-II participants and Study Management Group for their invaluable contributions to this research. The authors would also like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, and cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. David G. Cox is the recipient of a grant from the French Ligue Contre le Cancer, Comité de Savoie. Sophie Blein is the recipient of a CIFRE fellowship from the French ANRT and the LYRIC program.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

This work was funded by the U.S. National Institutes of Health, National Cancer Institute (cooperative agreements U01-CA98233 to David J. Hunter, U01-CA98710 to Michael J. Thun, U01-CA98216 to Elio Riboli and Rudolf Kaaks, and U01-CA98758 to Brian E. Henderson, and Intramural Research Program of NIH/NCI, Division of Cancer Epidemiology and Genetics). The American Cancer Society (ACS) funds the creation, maintenance, and updation of the Cancer Prevention Study-II (CPS-II) cohort.