摘要：A germline 29.5-kb deletion variant removes the 3’ end of the
APOBEC3A gene and a large part of
APOBEC3B, creating a hybrid gene that has been linked to increased APOBEC3 activity and DNA damage in human cancers. We genotyped the
APOBEC3A/B deletion in hospital-based samples of 1398 Norwegian epithelial ovarian cancer patients without detected
BRCA1/2 germline mutations and compared to 1,918 healthy female controls, to assess the potential cancer risk associated with the deletion. We observed an association between
APOBEC3A/B status and reduced risk for ovarian cancer (OR = 0.75; CI = 0.61–0.91;
p = 0.003) applying the dominant model. Similar results were found in other models. The association was observed both in non-serous and serous cases (dominant model: OR = 0.69; CI = 0.50–0.95;
p = 0.018 and OR = 0.77; CI = 0.62–0.96;
p = 0.019, respectively) as well as within high-grade serous cases (dominant model: OR = 0.79; CI = 0.59–1.05). For validation purposes, we mined an available large multinational GWAS-based data set of > 18,000 cases and > 26,000 controls for SNP rs12628403, known to be in linkage disequilibrium with the
APOBEC3A/B deletion. We found a non-significant trend for SNP rs12628403 being linked to reduced risk of ovarian cancer in general and similar trends for all subtypes. For clear cell cancers, the risk reduction reached significance (OR = 0.85; CI = 0.69–1.00).
