Association between polymorphisms in segregation genes BUB1B and TTK and gastric cancer risk

Abstract

Background: Malignant transformation of normal gastric cells is a complex and multistep process, resulting in development of heterogeneous tumors. Susceptible genetic background, accumulation of genetic changes, and environmental factors play an important role in gastric carcinogenesis. Single nucleotide polymorphisms (SNPs) in mitotic segregation genes could be responsible for inducing the slow process of accumulation of genetic changes, leading to genome instability.

Methods: We performed a case-control study of polymorphisms in mitotic kinases TTK rs151658 and BUB1B rs1031963 and rs1801376 to assess their effects on gastric cancer risk. We examined the TTK abundance in gastric cancer tissues using immunoblot analysis.

Results: C/G genotype in rs151658 was more frequent in patients with diffuse type of gastric cancer and G/G genotype was more common in intestinal types of gastric cancers (p=0.049). Polymorphic genotype A/A in rs1801376 was associated with higher risk for developing diffuse type of gastric cancer in female population (p=0.007), whereas A/A frequencies were increased in male patients with subserosa tumor cell infiltration (p=0.009). T/T genotype in rs1031963 was associated with well differentiated tumors (p=0.035). TT+CT genotypes in rs1031963 and GG+AG genotypes in rs1801376 were significantly associated with gastric cancer risk (dominant model; OR=2,929, 95% CI: 1.281-6.700; p=0.017 and dominant model; OR=0,364, 95% CI: 0.192-0.691; p=0.003 respectively).

Conclusions: Our results indicate that polymorphisms in mitotic kinases TTK and BUB1B may contribute to gastric tumorigenesis and risk of tumor development and could be useful in clinical setting for developing new prognostic and diagnostic approaches.