Genetic polymorphism in () gene is associated with keratinocyte skin cancer in a cohort of renal transplant recipients.

BACKGROUND

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.

OBJECTIVE

We sought to find further genetic variation in and overlap genes that may be associated with a diagnosis of KC in RTRs.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.