JCO abstract: Breast and Ovarian Cancer Risk and Risk Reduction in Jewish BRCA1/2 Mutation Carriers (185delAG, 5382insC, 6174delT)

Breast and Ovarian Cancer Risk and Risk Reduction in Jewish BRCA1/2 Mutation Carriers

Purpose 

Mutations in BRCA1/2 dramatically increase the risk of both breast and ovarian cancers. Three mutations in these genes (185delAG, 5382insC, and 6174delT) occur at high frequency in Ashkenazi Jews. We evaluated how these common Jewish mutations (CJMs) affect cancer risks and risk reduction. 

Methods 

Our cohort comprised 4,649 women with disease-associated BRCA1/2 mutations from 22 centers in the Prevention and Observation of Surgical End Points Consortium. Of these women, 969 were self-identified Jewish women. Cox proportional hazards models were used to estimate breast and ovarian cancer risks, as well as risk reduction from risk-reducing salpingo-oophorectomy (RRSO), by CJM and self-identified Jewish status. 

Results 

Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54% v 41%, respectively). Relative risks of cancer varied by CJM, with the relative risk of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers. No significant difference was seen in cancer risk reduction after RRSO among subgroups. 

Conclusion 

Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation in larger prospective and population-based cohort studies before being integrated into clinical care.

full free access: PLoS Medicine: Strengthening the Reporting of Genetic Risk Prediction Studies: The GRIPS Statement (multinational)

Summary Points

• The rapid and continuing progress in gene discovery for complex diseases is fueling interest in the potential application of genetic risk models for clinical and public health practice.
• The number of studies assessing the predictive ability is steadily increasing, but the quality and completeness of reporting varies.
• A multidisciplinary workshop sponsored by the Human Genome Epidemiology Network developed a checklist of 25 items recommended for strengthening the reporting of Genetic RIsk Prediction Studies (GRIPS), building on the principles established by prior reporting guidelines.
• These recommendations aim to enhance the transparency of study reporting, and thereby to improve the synthesis and application of information from multiple studies that might differ in design, conduct, or analysis.
• A detailed Explanation and Elaboration document is published as supporting information (Text S1).