Abstract 15: Interaction between retinol transporter genes and alcohol on the risk of head and neck cancer.

Abstract

Abstract Background: Alcohol is a major risk factor for head and neck cancer (HNC). The metabolism of ethanol can disrupt the metabolism of retinoic acid because the two pathways share some key enzymes. Retinoic acid is involved in cell growth, differentiation, and apoptosis, which when dysregulated may lead to the development of cancer. A previous genome-wide association study reported an association between single nucleotide polymorphisms (SNPs) in two retinol transporter genes (TTR and RBP4) and serum retinol level (1). The current study evaluates the interaction between alcohol consumption and SNPs in TTR and RBP4 on the risk of HNC. Methods: 223 incident cases of HNC and 214 sex- and age- matched controls were recruited from the department of otolaryngology and department of stomatology. In-person interviews were conducted to collect information on the use of alcohol, cigarette, and betel quid. Three tag-SNPs of TTR and 8 tag-SNPs of RBP4 were genotyped using the Taqman-based real-time PCR method or mass spectrometry-based detection method. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of HNC risk associated with each SNP and to evaluate the joint influence of SNPs and alcohol consumption on HNC risk, adjusted for age, sex, education, cigarette smoking and betel quid use. Results: No significant association between HNC risk and any of the 11 tag-SNPs was observed. However, three SNPs of RBP4 appeared to modify the relationship between alcohol consumption and HNC risk. After combining the three SNPs into a polygenic risk score, the results showed that those who drank alcohol daily had a different risk of HNC, depending on the number of variant alleles (0 to 2 variant alleles: OR=1.2, 95% CI: 0.7-2.1; 3 or more variant alleles: OR=2.9, 95% CI: 1.1-7.9; interaction P-value = 0.01) Conclusion: The association between HNC risk and alcohol consumption is modified by the polymorphisms of RBP4. Citation Format: Jeffrey S. Chang, Jenn-Ren Hsiao, Tung-Yiu Wong, Sen-Tien Tsai, Chun-Yen Ou, Hung-I Lo, Cheng-Chih Huang, Wei-Ting Lee, Ken-Chung Chen, Jehn-Shyun Huang, Yi-Hui Wang, Ya-Ling Weng, Han-Chien Yang. Interaction between retinol transporter genes and alcohol on the risk of head and neck cancer. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 15.