<abstract xmlns="http://www.w3.org/1999/xhtml"><sec><h3>Background</h3><p>Malignant 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.</p></sec><sec><h3>Patients and methods</h3><p>We performed a case-control study of polymorphisms in mitotic kinases <italic>TTK</italic> rs151658 and <italic>BUB1B</italic> rs1031963 and rs1801376 to assess their effects on gastric cancer risk. We examined the <italic>TTK</italic> abundance in gastric cancer tissues using immunoblot analysis.</p></sec><sec><h3>Results</h3><p>C/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).</p></sec><sec><h3>Conclusions</h3><p>Our results suggest that polymorphisms in mitotic kinases <italic>TTK</italic> and <italic>BUB1B</italic> 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.</p></sec></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.

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

University of Ljubljana, Faculty of Medicine, Institute of Biochemistry, Ljubljana, Slovenia

University Clinical Hospital Ljubljana, Department of Obstetrics and Gynecology, Department of Gynecological Pathology and Cytology, Ljubljana, Slovenia

Radiology and Oncology

BackgroundMalignant transformation of normal gastric cells is a complex and multistep process, resulting in development of heterogeneous tumours. Susceptible...

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

Article Category: Research Article

Publié en ligne: 19 juil. 2016

Pages: 297 - 307

Reçu: 13 mars 2015

Accepté: 09 août 2015

DOI: https://doi.org/10.1515/raon-2015-0047

© 2016 Fazekas and Porvázsnyik, published by De Gruyter Open

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