Background: To find support for risk-modifying genes in breast cancer, a haplotype GWAS in sporadic breast cancer cases was undertaken. The results were compared with the results from previous analyses in familial cases and all cases from the same Swedish cohort. Methods: In total, 2550 women with sporadic invasive breast cancer and 5021 healthy controls were included in a sliding-window haplotype GWAS using PLINK 1.07. Results: The analysis of sporadic cases confirmed the loci on chromosomes 10q26.13, 11q13.3, and 16q12.1 and suggested one novel locus on chromosome 12p11.21 (OR = 1.42 p = 4.55 × 10⁻⁸). A comparison between these loci and the same loci in the analyses of familial cases and all breast cancer cases was undertaken. Conclusions: Haplotype GWAS in sporadic cases of Swedish breast cancer cases supported known risk loci and suggested another risk locus. The loci identified in the analysis of sporadic and all breast cancer cases were suggested to act as modifiers of the risk of breast cancer. Haplotype analysis identified other loci with higher odds ratios than single-variant analysis. Further studies are needed to find out how to best include the findings in breast cancer prevention.

FANCM germline protein truncating variants (PTVs) are moderate-risk factors for ER-negative breast cancer. We previously described the spectrum of FANCM PTVs in 114 European breast cancer cases. In the present, larger cohort, we report the spectrum and frequency of four common and 62 rare FANCM PTVs found in 274 carriers detected among 44,803 breast cancer cases. We confirmed that p.Gln1701* was the most common PTV in Northern Europe with lower frequencies in Southern Europe. In contrast, p.Gly1906Alafs*12 was the most common PTV in Southern Europe with decreasing frequencies in Central and Northern Europe. We verified that p.Arg658* was prevalent in Central Europe and had highest frequencies in Eastern Europe. We also confirmed that the fourth most common PTV, p.Gln498Thrfs*7, might be a founder variant from Lithuania. Based on the frequency distribution of the carriers of rare PTVs, we showed that the FANCM PTVs spectra in Southwestern and Central Europe were much more heterogeneous than those from Northeastern Europe. These findings will inform the development of more efficient FANCM genetic testing strategies for breast cancer cases from specific European populations.