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Association of TGF-β1 Genetic Variants with HPV16-positive Oropharyngeal Cancer

Purpose: Transforming growth factor-β1 (TGF-β1) plays an important role in inflammation and immune responses, which control the human papillomavirus (HPV) clearance and escape of immune surveillance, and may contribute to genetic susceptibility to HPV16 infection. Experimental Design: In this case series study, we analyzed the HPV16 status in tumor specimens and genotyped three TGF-β1 polymorphisms using genomic DNA from the blood of 200 squamous cell carcinoma of the oropharynx (SCCOP) cases. We calculated odds ratio (OR) and 95% confidence intervals (95% CI) in univariate and multivariable logistic regression models to examine the association between the TGF-β1 polymorphisms and HPV16 status in SCCOP. Results: Compared with those with the common homozygous genotype, the TGF-β1 T869C variant genotypes were significantly associated with HPV16-positive tumor status among patients with SCCOP (OR, 1.97; 95% CI, 1.03-3.76), but no significant association was observed for the TGF-β1 C509T or G915C polymorphism. When all variant genotypes were combined, however, SCCOP patients carrying genotypes with any of these TGF-β1 variants were more than twice as likely to have an HPV16-positive tumor (OR, 2.28; 95% CI, 1.16-4.50) as patients with no variant genotypes. The stratified analysis showed that those under 54 years of age, non-Hispanic white patients, never smokers, and never drinkers with any variant TGF-β1 genotypes were also more likely to have HPV16-positive tumors. Conclusions: TGF-β1 polymorphisms may serve as a susceptibility marker for tumor HPV16 status among SCCOP patients, particularly those who were never smokers and never drinkers. Large studies are needed to validate our findings. Clin Cancer Res; 16(5); 1416–22