Single Nucleotide Polymorphisms on Toll-like Receptor-4 and the Risk of Developing Skin Cancer

Exposure to solar 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 the detrimental effects of acute and chronic UV exposure and skin cancer in mice. Single nucleotide polymorphisms (SNPs) on the TLR4 gene have been reported to increase or decrease susceptibility to various cancers in other organs. There is limited information on TLR4 SNPs and susceptibility to human keratinocyte carcinomas. The study's objective is to test the association between TLR4 SNPs and the risk of developing keratinocyte carcinomas. Skin cancer patients and controls at the 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 SNPs. Descriptive analytics were used to describe the cohort. Multivariable logistic regression models were used to assess the association between TLR4 SNPs and skin cancer risk. The sample consisted of a cohort of 93 skin cancer patients over the age of 50 and 94 controls; 33.3% of cases and 44.7% of controls were females; 12.9% of cases and 17% of controls had a TLR4 SNP. The most common SNP was D299G/T399I in 9.7% of skin cancer patients and 13.8% of controls. We did not find a statistically significant association between the D299G/T399I SNP and skin cancer (odds ratio (OR) = 0.34, 95% CI: 0.11, 1.07, p = 0.065) adjusting for age, sex, eye color, actinic keratosis, sunscreen use and reapplication, and family history of skin cancer. Based on our findings from our limited cohort of participants, we found some protective effect for the TLR4 SNP for skin cancer, which was not statistically significant. Validation of these findings in a larger cohort is warranted.