BRCA2—Branching Out Too?
A partir de données portant sur 5 942 patients et 8 086 témoins dans 9 pays, cette étude met en évidence l'association entre un variant rare du gène BRCA2 et le risque de cancer des voies aérodigestives supérieures
In this issue of the Journal, Delahaye-Sourdeix et al. (1) report a statistically significant association (odds ratio [OR] = 2.53) between a rare (minor allele frequency [MAF] < 0.01) truncating BRCA2 genetic variant, K3326X (rs11571833) and risk of upper aero-digestive tract (UADT) cancer. Their data are derived from combining nine international studies. This finding follows on the published association of K3326X with lung cancer (2), driven primarily by a relationship with squamous rather than adenocarcinoma histology. K3326X was recently also shown to confer a 1.26-fold increased breast cancer risk (3) and has been suggested previously as a risk factor for both esophageal (4) and pancreatic cancers (5). This study is of interest for several reasons. It confirms a robust association between a variant in BRCA2 and smoking-related cancers. Furthermore, the strength of the associations noted for these smoking-related cancers, specifically lung, UADT, pancreatic, and esophageal (all above two-fold), far exceeds the modest 26% increase in breast cancer risk and odds ratios associated with the top hits reported for virtually all GWAS of other conditions. Delahaye-Sourdeix et al. (1) estimated a 2.5-fold increase in risk for UADT cancer per variant allele …