Gastric cardia carcinoma is associated with the promoter -77T>C gene polymorphism of X-ray cross-complementing group 1 (XRCC1)

X-ray repair cross complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the bas-excision repair pathway. Several single-nucleotide polymorphisms in the XRCC1 gene are identified and related with increased cancer risk development. In particular, the -77T > C polymorphism located on the promoter region relates with lung cancer risk development. The aim of this study is to analyze the -77T > C allelic frequencies in a population composed of 456 primary gastric cancer patients (GC) and 507 blood donor controls.GC patients were observed at the University of Siena, Italy; clinicopathological data and family history were available for the cancer group. The control group is composed of blood donors. Constitutional genomic DNA was PCR amplified, and XRCC1 -77T > C was detected using restriction enzyme BsrB I and analyzed in a 3% agarose gel.The -77C > C homozygous genotype was significantly associated with increased risk of gastric cardia carcinoma (p = 0.023) with an odds ratio of 1.65 (95% confidence interval 1.14 to 2.4). In the family history stratification, we report a significant association (p = 0.043) between the -77T > C polymorphism and GC cases with familial lung cancer aggregation.Our results suggest that the XRCC1 -77T > C polymorphism is a relevant host susceptibility factor for gastric cardia cancer development and specific subsets of familial clustering of GC.