Do Female BRCA2 Pathogenic Variant Carriers Have an Increased Risk of Lung Cancer?

Abstract

Li et al 1 recently reported the association between risk of 22 cancers and BRCA1 and BRCA2 pathogenic variants (PVs) in the Consortium of Investigators of Modifiers of the BRCA1/2 cohort. Among 3,184 BRCA1 and 2,157 BRCA2 families, BRCA1 and BRCA2 PVs were associated with an increased risk of male breast, pancreatic, and stomach cancer; male BRCA2 PV carriers had also an increased prostate cancer risk. The authors did not observe increased risks for other cancers, lung cancer in particular. Indeed, overall lung cancer relative risk (RR) was 1.37 (95% CI, 0.85 to 2.21) and 1.13 (95% CI, 0.63 to 2.03) for BRCA1 and BRCA2, respectively. Nevertheless, it would be premature, in our opinion, to rule out an association between BRCA2 PV and lung cancer for the following reasons:

Reply to V. Fallet et al

“…Although we did not observe an overall association with lung cancer risk for either BRCA1 or BRCA2 PV carriers, Fallet et al 1 suggested that the role of BRCA2 PVs in lung cancer should remain open for discussion. We agree with Fallet et al 1 that additional data are required to clarify these associations. Here, we would like to highlight a few methodological considerations in interpreting the results.…”

“…Fallet et al 1 also indicated that our analysis included one of the lowest percentages of families in the lung cancer analysis. As mentioned in our study, we excluded any study groups in which underreporting was likely in cancer-specific analyses.…”

“…Fallet et al 1 commented on our study, 2 in which we evaluated the associations of germline BRCA1 and BRCA2 ( BRCA1 / 2 ) pathogenic variants (PVs) with risks of 22 cancers, other than female breast and ovarian cancers. Although we did not observe an overall association with lung cancer risk for either BRCA1 or BRCA2 PV carriers, Fallet et al 1 suggested that the role of BRCA2 PVs in lung cancer should remain open for discussion. We agree with Fallet et al 1 that additional data are required to clarify these associations.…”

“…Fallet et al 1 argued that there might be a sex-specific association between BRCA2 PVs and lung cancer risk, possibly confounded or modified by other risk factors, including smoking. We observed an association for female BRCA2 PV carriers with a relative risk (RR) of 2.84 (95% CI, 1.23 to 6.60), but not for male BRCA2 PV carriers (RR 5 0.81; 95% CI, 0.39 to 1.69).…”