Yusuf Nabiha, Sharafeldin Noha, Saleem Mohammad, Callens Tom, Messiaen Ludwine M, Elmets Craig A
Department of Dermatology, University of Alabama at Birmingham, 1670 University Boulevard VH566A, Birmingham, AL 35294, USA.
Department of Hematology and Oncology, UAB Heersink School of Medicine, Birmingham, AL 35233, USA.
Int J Mol Sci. 2024 Nov 27;25(23):12728. doi: 10.3390/ijms252312728.
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 gene have been reported to increase or decrease susceptibility to various cancers in other organs. There is limited information on SNPs and susceptibility to human keratinocyte carcinomas. The study's objective is to test the association between 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 SNPs. Descriptive analytics were used to describe the cohort. Multivariable logistic regression models were used to assess the association between 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 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, = 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 SNP for skin cancer, which was not statistically significant. Validation of these findings in a larger cohort is warranted.
暴露于太阳紫外线（UV）辐射是皮肤癌公认的风险因素。Toll样受体4（TLR4）介导的免疫失调已成为急性和慢性紫外线暴露及小鼠皮肤癌产生有害影响的关键机制。据报道，该基因上的单核苷酸多态性（SNP）会增加或降低其他器官对各种癌症的易感性。关于SNP与人类角质形成细胞癌易感性的信息有限。该研究的目的是测试SNP与发生角质形成细胞癌风险之间的关联。阿拉巴马大学伯明翰分校的皮肤癌患者和对照组完成了一项关于皮肤癌个人和家族史以及防晒霜使用和晒黑倾向的横断面调查。从参与者身上采集外周血样本，提取DNA以对SNP进行基因分型。描述性分析用于描述该队列。多变量逻辑回归模型用于评估SNP与皮肤癌风险之间的关联。样本包括93名50岁以上的皮肤癌患者和94名对照；33.3%的病例和44.7%的对照为女性；12.9%的病例和17%的对照有一个SNP。最常见的SNP是D299G/T399I，在9.7%的皮肤癌患者和13.8%的对照中出现。在调整年龄、性别、眼睛颜色、光化性角化病、防晒霜使用和重新涂抹以及皮肤癌家族史后，我们未发现D299G/T399I SNP与皮肤癌之间存在统计学上的显著关联（优势比（OR）=0.34，95%置信区间：0.11，1.07，P = 0.065）。基于我们在有限参与者队列中的发现，我们发现该SNP对皮肤癌有一定的保护作用，但无统计学意义。有必要在更大的队列中验证这些发现。
