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 risk 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.

Endothelial Cell Bioenergetics and Mitochondrial DNA Damage Differ in Humans Having African or West Eurasian Maternal Ancestry

“…Finally, the 10398 SNP utilized to segregate mtDNA haplogroups into “northern and southern” latitudes has been previously associated certain neurodegenerative diseases and breast cancer 38, 66 . However, these findings are controversial 37, 40, 41 and whether this SNP is directly related to the differences observed in these studies is not yet known. Direct comparisons between closely related mtDNA haplogroups within the West Eurasia may provide additional insights into this question.…”

“…This site is present in maternal lineages which are ubiquitous in African populations (L0 – L7) and also in a specific subset of West Eurasian mtDNAs (I, J, K) proposed to have Middle Eastern origins, but is absent in the remaining West Eurasian maternal lineages (haplogroups H, T, U, V, W, X) 35, 36 . Although this SNP has also been proposed to increase risk of invasive breast cancer in African American women when cancer exists, many studies investigating this issue have been conflicting 37–41 . Its use in the study herein was simply to segregate haplogroups into “northern” (DdeI −) or “southern” (DdeI +) latitudes.…”

Biobehavioral and neuroendocrine correlates of antioxidant enzyme activity in ovarian carcinoma

“…The existence of a relationship between MnSOD and GPx1 variants and cancer risk has been suggested (Blein et al, 2014). Thus, future pre-clinical work should establish causality and the role of genetic variants so that therapeutic interventions can be appropriately targeted.…”

Lack of Association Between Superoxide Dismutase Gene Polymorphism and Malignant Lymphoproliferative Disorders

“…Our study compared polymorphism of superoxide dismutase type 2 (SOD2) in a healthy population compared to (29). Therefore, it seems that the polymorphisms within the SOD gene can be considered as risk factors for prostate cancer.…”