Disease-Associated Risk Variants in ANRIL Are Associated with Tumor-Infiltrating Lymphocyte Presence in Primary Melanomas in the Population-Based GEM Study

Genome-wide association studies have reported that genetic variation at ( ) is associated with risk of several chronic diseases including coronary artery disease, coronary artery calcification, myocardial infarction, and type 2 diabetes mellitus. is located at the locus, which encodes multiple melanoma tumor suppressors. We investigated the association of these variants with melanoma prognostic characteristics. The Genes, Environment, and Melanoma Study enrolled 3,285 European origin participants with incident invasive primary melanoma. For each of ten disease-associated SNPs at or near , we used linear and logistic regression modeling to estimate, respectively, the per allele mean changes in log of Breslow thickness and ORs for presence of ulceration and tumor-infiltrating lymphocytes (TIL). We also assessed effect modification by tumor mutational status. Rs518394, rs10965215, and rs564398 passed false discovery and were each associated ( ≤ 0.005) with TILs, although only rs564398 was independently associated ( = 0.0005) with TILs. Stratified by mutational status, rs564398*A was significantly positively associated with TILs among mutant, but not wild-type, cases. We did not find SNP associations with Breslow thickness or ulceration. rs564398 was associated with TIL presence in primary melanomas, and this association may be limited to -mutant cases. Pathways related to variants warrant exploration in relationship to TILs in melanoma, especially given the impact of TILs on immunotherapy and survival.