Pancreatic cancer cluster region identified in BRCA2

Pancreatic cancer has a poor prognosis. Lack of diagnostic markers prevents its early diagnosis and treatment. Pathogenic germline variation in BRCA1 and BRCA2 (BRCA) is genetic predisposition for cancer. The location of variants in different regions in BRCA is non-randomly enriched in different types of cancer as shown by the breast cancer cluster region (BCCR), ovarian cancer cluster region (OCCR) and prostate cancer cluster region (PrCCR). Although pathogenic BRCA variation also contributes to pancreatic cancer, no pancreatic cancer cluster region (PcCCR) in BRCA1 or BRCA2 has been identified due to the relatively low incidence of pancreatic cancer and the lack of sufficient variation data from pancreatic cancer. Through comprehensive data mining, we identified 215 BRCA pathogenic variants (PVs) (71 in BRCA1 and 144 in BRCA2) from 27 118 pancreatic cancer cases. Through mapping the variants, we identified a region non-randomly enriched in pancreatic cancer between BRCA2 c.3515 and c.6787. This region contained 59 BRCA2 PVs and included 57% of pancreatic cancer cases (95% CI 43% to 70%). The PcCCR did not overlap with the BCCR and PrCCR but overlapped with the BRCA2 OCCR, highlighting that this region may play similar aetiological roles in pancreatic cancer and ovarian cancer.