Griffin L, Ho L, Akhurst R J, Arron S T, Boggs J M E, Conlon P, O'Kelly P, Toland A E, Epstein E H, Balmain A, Bastian B C, Moloney F J, Murphy G M, Laing M E
Department of Dermatology University Hospital Galway Galway Ireland.
Department of Dermatology Beaumont Hospital Dublin 9 Ireland.
Skin Health Dis. 2022 Feb 2;2(2):e95. doi: 10.1002/ski2.95. eCollection 2022 Jun.
Renal transplant recipients (RTRs) are at increased risk of keratinocyte cancer (KC), especially cutaneous squamous cell carcinoma (cSCC). Previous studies identified a genetic variant of the () gene, C677T, which conferred a risk for diagnosis of cSCC in Irish RTRs.
We sought to find further genetic variation in and overlap genes that may be associated with a diagnosis of KC in RTRs.
Genotyping of a combined RTR population ( = 821) from two centres, Ireland ( = 546) and the USA ( = 275), was performed. This included 290 RTRs with KC and 444 without. Eleven single nucleotide polymorphisms (SNPs) in the gene and seven in the overlap gene ( were evaluated and association explored by time to event analysis (from transplant to first KC) using Cox proportional hazards model.
Polymorphism at (rs9651118) was significantly associated with KC in RTRs (HR 1.50, 95% CI 1.17-1.91, < 0.00061) and cSCC (HR 1.63, 95% CI 1.14-2.34, = 0.007). A separate SNP, C677T, was also significantly associated with KC in the Irish population (HR 1.31, 95% CI 1.05-1.63, = 0.016), but not American RTRs.
We report the association of a SNP in the overlap gene, and KC in a combined RTR population. While the exact function of is not known, it is proposed to be involved in folate availability. Future applications could include incorporation in a polygenic risk score for KC in RTRs to help identify those at increased risk beyond traditional risk factor assessment.
肾移植受者（RTRs）患角质形成细胞癌（KC）的风险增加，尤其是皮肤鳞状细胞癌（cSCC）。先前的研究确定了（）基因的一种基因变体C677T，其增加了爱尔兰肾移植受者患皮肤鳞状细胞癌的风险。
我们试图在与肾移植受者患KC可能相关的基因及重叠基因中寻找更多的基因变异。
对来自爱尔兰（n = 546）和美国（n = 275）两个中心的821例肾移植受者组成的联合群体进行基因分型。其中包括290例患KC的肾移植受者和444例未患KC的肾移植受者。对该基因中的11个单核苷酸多态性（SNPs）以及重叠基因中的7个单核苷酸多态性进行评估，并使用Cox比例风险模型通过事件发生时间分析（从移植到首次发生KC）来探索其关联性。
该基因的多态性（rs9651118）与肾移植受者患KC显著相关（风险比1.50，95%置信区间1.17 - 1.91，P < 0.00061）以及与皮肤鳞状细胞癌相关（风险比1.63，95%置信区间1.14 - 2.34，P = 0.007）。另一个单核苷酸多态性，即该基因的C677T，在爱尔兰人群中也与患KC显著相关（风险比1.31，95%置信区间1.05 - 1.63，P = 0.016），但在美国肾移植受者中并非如此。
我们报告了在联合肾移植受者群体中，该基因重叠基因中的一个单核苷酸多态性与患KC之间的关联。虽然该基因的确切功能尚不清楚，但推测其与叶酸的可利用性有关。未来的应用可能包括将其纳入肾移植受者患KC的多基因风险评分中，以帮助识别那些在传统风险因素评估之外风险增加的患者。
