Blood molybdenum level as a marker of cancer risk among BRCA1 carriers

Abstract

Purpose:A large proportion of ovarian and breast cancer cases are due to genetic predisposition. Women with a mutation in the BRCA1 gene have an up to an 80% chance of developing breast cancer and 40% chance of developing ovarian cancer. No studies to date assess exposure to molybdenum and cancer risk. The purpose of our study was to see if exposure to molybdenum modifies cancer risk in BRCA1 mutation carriers. Material and Methods: The study included 989 initially unaffected women with a BRCA1 mutation. The mean follow-up time was 6.8 years. During this time, 172 cancers occurred including 121 breast, 29 ovarian and 22 cancers at other sites. The cohort was stratified into three categories (tertiles) based on the blood level of molybdenum (<0.54 µg/L, 0.54-0.70 µg/L and >0.70 µg/L) with the lowest tertile forming the reference group. Cox proportional hazards models were used to model the association between blood molybdenum levels and cancer incidence. Results:A high blood molybdenum level (>0.70 µg/L) was associated with a significantly increased risk of developing ovarian cancer (HR = 5.55; 95%CI: 1.59-19.4; p = 0.007) and of any cancer (HR = 1.74; 95%CI: 1.17-2.61; p = 0.007) but not of breast cancer (HR = 1.46, CI= 0.91-2.33; p = 0.12). Conclusion:It is possible that lowering molybdenum levels may reduce the risk of cancer among women with a pathogenic germline variant in BRCA1.