PubMed | Karolinska Institutet, University of Newcastle, Dr. Horst Schmidt Kliniken Wiesbaden, Medical University of South Carolina and 104 more.
Type: Journal Article | Journal: Journal of medical genetics | Year: 2016
The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study.We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42671 cases and 42164 controls), as well as prostate (22301 cases and 22320 controls) and ovarian (14542 cases and 23491 controls) cancer risk, for each variant.For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.110This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.