Genome-wide association studies of pigmentation and skin cancer: a review and meta-analysis

Abstract

Recent genome-wide association studies (GWAS) identified genetic loci associated with pigmentation, nevi, and skin cancer. We performed a review and meta-analysis of GWAS results, grouping them into four categories: (i) loci associated with pigmentation (hair, eye, and/or skin color), cutaneous UV-response (sun sensitivity and/or freckling), and skin cancer; (ii) loci associated with nevi and melanoma; (iii) loci associated with pigmentation and/or cutaneous UV-response but not skin cancer; and (iv) loci associated distinctly with skin cancer, mostly basal cell carcinoma, but not pigmentation or cutaneous UV-response. These findings suggest at least two pathways for melanoma development (via pigmentation and via nevi), and two pathways for basal cell carcinoma development (via pigmentation and independent of pigmentation). However, further work is necessary to separate the association with skin cancer from the association with pigmentation. As with any GWAS, the identified loci may not include the causal variants and may need confirmation by direct genome sequencing.

Figure 1

Association between SNPs and melanoma risk from meta-analysis of GWAS and replication studies. SNPs were included if reported in at least three studies. Fixed effects meta-analyses are used for rs7023329, rs1126809, rs910873, and rs1885120 SNPs, whose results showed no heterogeneity across studies; for the remaining SNPs, results based on random effects model are shown. Black squares indicate the odds ratios (OR), with the size of the square inversely proportional to its variance. Horizontal lines represent 95% confidence intervals (CI). All heterogeneity test results and estimates based on both fixed and random effects models for all SNPs shown here as well as meta-analysis results of SNPs based on two studies only are reported in Supplemental Table Ig.