MRC1 and breast cancer: Due to differences in study design, cohort ascertainment, and overall proportion of MSH6 and PMS2 PV carriers, many previous studies evaluating breast cancer risk in association with the MMR genes are not suitable for direct comparison with our findings.15,16 In one retrospective study with a design more similar to ours, Engel et al.21 found an almost twofold increased breast cancer risk in a cohort of 1,107 women with PVs in the MMR genes (SIR = 1.9; 95% CI, 1.4–2.4).