Ercc2 Polymorphism Asp711asp Is Associated With Risk Of Young-Onset Pancreatic Cancer.

9688 Background:DNA repair has become an area of intense research in the study of human malignancies. Though germline mutations in DNA repair genes such as Fanconi anemia genes and BRCA2 have been studied in pancreatic cancer, common polymorphisms of the more than 100 other DNA repair genes have not been well studied. Methods:Since 2000, we have conducted a Mayo Clinic-based case-control study consisting of ultra-rapidly recruited patients with the diagnosis of pancreatic adenocarcinoma. Controls were selected from a pool of healthy patients receiving screening colonoscopies. In all, 481 cases of pancreatic cancer (all ages) were compared with 623 controls. Germline DNA was collected from blood samples, and analyzed by Pyrosequencing of known polymorphisms of three DNA repair genes, ERCC1 A118 (rs3177700), ERCC2 A711(rs1052555), and OGG S326C (rs 1052133). Frequencies were compared using the Cochran Armitage Trend Test (one-sided Pr > Z). Young-onset cases (<60 yrs.) were analyzed as a subgroup. Results:The AA and AG genotypes of the ERCC2 Asp711Asp variant were more frequently noted in the young onset cases compared with either all controls (p=0.023) or young (<60) controls (p=0.015). No difference was seen in the other two loci investigated. Conclusions:Preliminary data shows that genotypes containing the A allele of the DNA repair gene ERCC2 may increase risk for young-onset pancreatic cancer. Further confirmation in follow-up studies is needed. Author Disclosure Genotype Frequencies for All Cases and Controls and those under 60 years of Age Gene (Locus) Genotype All Cases (n=481) All Controls (n=623) Cases < age 60 (n=136) Controls < age 60 (n=191) ERCC2 (Asp711Asp) A/A 67 (14%) 69 (11%) 21 (15%) 31 (11%) ERCC2 (Asp711Asp) A/G 203 (42%) 260 (43%) 64 (47%) 120 (41%) ERCC2 (Asp711Asp) G/G 211 (44%) 282 (46%) 51 (38%) 140 (48%) OGG1 (Ser326Cys) C/C 23 (5%) 42 (7%) 5 (4%) 16 (5%) OGG1 (Ser326Cys) C/G 181 (38%) 224 (37%) 52 (38%) 103 (35%) OGG1 (Ser326Cys) G/G 277 (58%) 345 (56%) 79 (58%) 173 (59%) ERCC1 (Asn118Asn) C/C 75 (16%) 85 (14%) 25 (18%) 42 (14%) ERCC1 (Asn118Asn) C/T 205 (43%) 282 (46%) 60 (44%) 129 (44%) ERCC1 (Asn118Asn) T/T 200 (42%) 245 (40%) 51 (38%) 121(41%) No significant financial relationships to disclose.