Osteopontin Promoter Polymorphisms are Associated With Susceptibility to Gastric Cancer

GOALS:To evaluate the significance of osteopontin (OPN) genotypes in the susceptibility to gastric cancer. BACKGROUND:The expression of OPN has been correlated with development, invasiveness, metastasis, and survival of gastric cancer, but the role of polymorphisms in the OPN promoter has not been investigated. STUDY:We enrolled 146 gastric cancer patients and 128 controls. DNA was extracted from peripheral blood leucocytes. Single-nucleotide polymorphisms (SNPs) in the OPN promoter (−66, −156, −443, −616, −1748, and −1776) were analyzed by pyrosequencing and direct sequencing methods. Logistic regression analyses were used to evaluate the associations between SNPs and development of gastric cancer. RESULTS:SNP −443 C/C and −616 T/T of the OPN promoter were significantly associated with gastric cancer [odds ratio (OR)=2.88; 95% confidence interval (CI), 1.16-7.12 and OR=1.95; 95% CI, 1.35-2.82, respectively]. Analysis of the combined effect of OPN promoter SNPs revealed that the combination of SNP −443 (T/C or C/C) and SNP −616 (T/T or T/G) had the most significant association with gastric cancer (OR=3.95; 95% CI, 1.58-9.90). CONCLUSIONS:Our results suggest that polymorphisms in the OPN promoter are associated with the development of gastric cancer, and the combination of SNP −443 (T/C or C/C) and −616 (T/T or T/G) most significantly increases susceptibility to gastric cancer.