Analysis of rs8067378 Polymorphism in the Risk of Uterine Cervical Cancer from a Polish Population and its Impact on Gasdermin B Expression

OBJECTIVE: We studied the role of the NC_000017.10:g.38051348A>G (rs8067378) single nucleotide polymorphism (SNP) located 9.5 kb downstream of gasdermin B (GSDMB), in the development and progression of cervical squamous cell carcinomas (SCC). METHODS: Using high-resolution melting curve analysis, we genotyped this SNP in patients with cervical SCC (n = 486) and controls (n = 511) from the Polish Caucasian population. Logistic regression analysis was used to adjust for the effect of confounders such as age, parity, oral contraceptive use, tobacco smoking, and menopausal status. The effect of this SNP on the expression of GSDMB was studied by reverse transcription and quantitative real-time polymerase chain reaction analysis of GSDMB transcript levels in SCC tissues. RESULTS: For all patients with SCC, the p trend value calculated for rs8067378 was statistically significant (p (trend) = 0.0019). The adjusted odds ratio for the G/G vs. A/A genotype was 1.304 (95% confidence interval 1.080–1.574, p = 0.0057) and the adjusted odds ratio for the G/A + G/G vs. A/A genotype was 1.444 (95% confidence interval 1.064–1.959, p = 0.0181). We also found a significant association of the rs8067378 SNP with tumor stages III, IV, and grade of differentiation G3, and with parity, oral contraceptive use, smoking, and women of postmenopausal age. We found increased GSDMB1 isoform transcripts in the cancerous and non-cancerous tissues from carriers of the G allele vs. carriers of the A/A genotype. CONCLUSIONS: The rs8067378 SNP variants may increase the expression of GSDMB and the risk of the development and progression of cervical SCC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40291-017-0256-1) contains supplementary material, which is available to authorized users.