Pancreatic cancer cluster region identified inBRCA2

Abstract

Pancreatic cancer has a poor prognosis. Lack of diagnostic markers prevents its early diagnosis and treatment. Pathogenic germline variation inBRCA1andBRCA2(BRCA) is genetic predisposition for cancer. The location of variants in different regions inBRCAis 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 pathogenicBRCAvariation also contributes to pancreatic cancer, no pancreatic cancer cluster region (PcCCR) inBRCA1orBRCA2has 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 215BRCApathogenic variants (PVs) (71 inBRCA1and 144 inBRCA2) from 27 118 pancreatic cancer cases. Through mapping the variants, we identified a region non-randomly enriched in pancreatic cancer betweenBRCA2c.3515 and c.6787. This region contained 59BRCA2PVs 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 theBRCA2OCCR, highlighting that this region may play similar aetiological roles in pancreatic cancer and ovarian cancer.