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

Abstract

BackgroundMalignant transformation of normal gastric cells is a complex and multistep process, resulting in development of heterogeneous tumours. 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.Patients and methodsWe 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.ResultsC/G genotype of 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 of 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 tumour cell infiltration (p = 0.009). T/T genotype of rs1031963 was associated with well differentiated tumours (p = 0.035). TT+CT genotypes of rs1031963 and GG+AG genotypes of 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).ConclusionsOur results suggest that polymorphisms in mitotic kinases TTK and BUB1B may contribute to gastric tumorigenesis and risk of tumour development. Further investigations on large populations and populations of different ethnicity are needed to determine their clinical utility.

Identification of five hub genes as monitoring biomarkers for breast cancer metastasis in silico

“…BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) encodes a kinase participating in the spindle checkpoint; this protein plays a critical role in the inhibition of the anaphase-promoting complex/cyclosome (APC/C) and functions in delaying the onset of anaphase and ensuring proper chromosome segregation [42]. The oncogene role of BUB1B has been observed in cancers such as prostate cancer, glioblastoma and gastric cancer [43][44][45]. BUB1B is overexpressed in breast cancer, and the level of BUB1B mRNA is significantly correlated with intrachromosomal instability [46].…”

Comprehensive analysis of differentially expressed genes associated with PLK1 in bladder cancer

“…Moreover, some studies have proven the role of BUB1B in cancers. BUB1B may contribute to gastric tumorigenesis and the risk of tumor development [ 15 ]. Overexpression of BUB1B in prostate cancer cells promotes cell proliferation and migration [ 16 ].…”

Single nucleotide polymorphisms rs911160 in AURKA and rs2289590 in AURKB mitotic checkpoint genes contribute to gastric cancer susceptibility

“…These variants were associated with reduced risk for the development of diffuse type, increased survival, and decreased probability for the development of poorly differentiated adenocarcinoma [Bao et al, ]. Two previous studies also revealed significant associations between genotypes of rs758099 in mitotic kinase AURKC and rs151658 in mitotic kinase TTK and histopathological variables of patients, including Lauren classification and the degree of differentiation [Hudler et al, ; Mesic et al, ].…”