Abstract 1157: Single nucleotide polymorphisms in ARHGAP17 are associated with pancreatic intraepithelial neoplasia in 2401 autopsied elderly patients

Abstract

Abstract Background: Aging, obesity, smoking, alcohol consumption, diabetes, and pancreatitis have been reported to be the risk factors for pancreatic cancer. There is much evidence showing that single nucleotide polymorphisms (SNPs), especially those in BCAR1, PDX1, ZNRF3, or TERT, influence one's predisposition to pancreatic cancers and survival. However, the association between SNP and pancreatic precancerous lesions is not yet clarified. In the present study, we clarified the clinicopathological features of precancerous lesions of the pancreas by examining autopsied elderly cases. Methods: We analyzed serial autopsy cases (men, 1326; women, 1075; mean age, 80.6) of pancreatic intraepithelial neoplasia (PanIN) and performed a comparative analysis based on the sex, age, and body mass index (BMI) of the patients. The SNPs were analyzed using HumanExome BeadChip. Results: The occurrence of PanIN increased with advanced age. Approximately, 60% of the elderly patients showed low-grade PanIN. The autopsy cases showed that the occurrence of low-grade PanIN was positively correlated with the female sex, advanced age, and increase in BMI. The SNPs of the ARHGAP17 gene, p.G782D (rs28365822) and rs1106576, were risk factors for PanIN (Table, P<0.0001, *adjusted with age and gender). Discussion: A high incidence of low-grade PanIN in the elderly might be related to the increased risk of pancreatic cancer in the elderly. Further studies are needed to clarify the role of SNPs of ARHGAP17 in the carcinogenesis of pancreatic cancer. Association between SNPs in ARHGAP17 and pancreatic intraepithelial neoplasiasGenotypePanIN (-)PanIN (+)P valueunadjustedadjusted*rs28365822(%)Chi squareDominant-FisherLogistic regressionOdds ratio(95% confidence interval)CC1028(99.1)1192(96.7)<0.00010.000040.00023.934.05TC9(0.9)41(3.3)(1.90-8.12)(1.94-8.47)TT0(0)0(0)GenotypePanIN (-)PanIN (+)P valueunadjustedadjusted*rs1106576(%)Chi squareDominant-FisherLogistic regressionOdds ratio(95% confidence interval)TT1027(99.1)1192(96.7)<0.00010.000040.00023.934.05TC9(0.9)41(3.3)(1.90-8.12)(1.94-8.47)CC0(0)0(0) Citation Format: Yoko Matsuda, Masashi Tanaka, Atsuko Seki, Keisuke Nonaka, Makoto Nishimura, Toshiyuki Ishiwata, Hisashi Yoshimura, Kaiyo Takubo, Tomio Arai. Single nucleotide polymorphisms in ARHGAP17 are associated with pancreatic intraepithelial neoplasia in 2401 autopsied elderly patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1157.