LB1656 Associations of single nucleotide polymorphisms on toll-like receptor-4 with risk of skin cancer

Background: Exposure to ultraviolet (UV) radiation is an established risk factor for skin cancer. Toll-like receptor-4 (TLR4) mediated immune dysregulation has emerged as a key mechanism for skin cancer in mice. Single nucleotide polymorphisms (SNPs) on TLR4 gene has been reported to increase or decrease the susceptibility to various cancers. TLR4 SNP was found to be associated with progression and survival of melanoma patients. There is limited information on TLR4 SNP and the susceptibility to skin cancer. Objective: To test the association between TLR4 SNPs and the risk of development of skin cancer. Methods: Skin cancer patients and controls at University of Alabama at Birmingham completed a cross-sectional survey on personal and family history of skin cancer as well as on sunscreen use and tanning proneness. Peripheral blood samples were obtained from participants and DNA was extracted to genotype the TLR4 SNP. Descriptive analytics were used to describe the cohort. Multivariable logistic regression models were used to assess the association of TLR4 SNPs and skin cancer risk. Results: The sample consisted of a cohort of 100 skin cancer patients and 102 controls; 64% of cases and 55.9% of controls were males; 12 (12%) of cases and 17 (16.7%) of controls had any TLR4 SNP. The most common SNP was D299G in 9 of 12 cases (9.3% overall cases) and 15 of 17 controls (15% overall controls). There was a statistically significant association between the D299G SNP and skin cancer (Odds ratio (OR) = 0.32, 95%CI: 0.10, 0.99, p=0.047) adjusting for sex, actinic keratosis, and sunscreen use and reapplication. Conclusion: Based on our findings from our limited cohort of participants, we found a significant protective effect for the TLR4SNP against skin cancer. Validation of these findings in a larger cohort is warranted.