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. 2016 Apr;25(4):714-20.
doi: 10.1158/1055-9965.EPI-15-1070. Epub 2016 Feb 12.

A Genome-Wide Association Study of Cutaneous Squamous Cell Carcinoma among European Descendants

Satu J Siiskonen  1 , Mingfeng Zhang  2 , Wen-Qing Li  3 , Liming Liang  4 , Peter Kraft  4 , Tamar Nijsten  1 , Jiali Han  5 , Abrar A Qureshi  6
Affiliations

A Genome-Wide Association Study of Cutaneous Squamous Cell Carcinoma among European Descendants

Satu J Siiskonen et al. Cancer Epidemiol Biomarkers Prev. 2016 Apr.

Abstract

Background: No GWAS on the risk of cutaneous squamous cell carcinoma (SCC) has been published. We conducted a multistage genome-wide association study (GWAS) to identify novel genetic loci for SCC.

Methods: The study included 745 SCC cases and 12,805 controls of European descent in the discovery stage and 531 SCC cases and 551 controls of European ancestry in the replication stage. We selected 64 independent loci that showed the most significant associations with SCC in the discovery stage (linkage disequilibrium r(2) < 0.4) for replication.

Results: Rs8063761 in the DEF8 gene on chromosome 16 showed the strongest association with SCC (P = 1.7 × 10(-9) in the combined set; P = 1.0 × 10(-6) in the discovery set and P = 4.1 × 10(-4) in the replication set). The variant allele of rs8063761 (T allele) was associated with a decreased expression of DEF8 (P = 1.2 × 10(-6)). Besides, we validated four other SNPs associated with SCC in the replication set, including rs9689649 in PARK2 gene (P = 2.7 × 10(-6) in combined set; P = 3.2 × 10(-5) in the discovery; and P = 0.02 in the replication), rs754626 in the SRC gene (P = 1.1 × 10(-6) in combined set; P = 1.4 × 10(-5) in the discovery and P = 0.02 in the replication), rs9643297 in ST3GAL1 gene (P = 8.2 × 10(-6) in combined set; P = 3.3 × 10(-5) in the discovery; and P = 0.04 in the replication), and rs17247181 in ERBB2IP gene (P = 4.2 × 10(-6) in combined set; P = 3.1 × 10(-5) in the discovery; and P = 0.048 in the replication).

Conclusion: Several genetic variants were associated with risk of SCC in a multistage GWAS of subjects of European ancestry.

Impact: Further studies are warranted to validate our finding and elucidate the genetic function of these variants. Cancer Epidemiol Biomarkers Prev; 25(4); 714-20. ©2016 AACR.

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Conflict of interest statement

Conflicts of Interest: Other authors declare no conflict of interest.

Figures

Figure 1
Figure 1. Regional plot of the DEF8 gene
Regional Manhattan Plots for the SCC GWAS within 200kb surrounding the DEF8 gene on chromosome 6.
See this image and copyright information in PMC

Comment in

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