Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma

• Published in: Nature communications Vol. 7; no. 1; pp. 12048 - 8
• Main Authors: Chahal, Harvind S., Lin, Yuan, Ransohoff, Katherine J., Hinds, David A., Wu, Wenting, Dai, Hong-Ji, Qureshi, Abrar A., Li, Wen-Qing, Kraft, Peter, Tang, Jean Y., Han, Jiali, Sarin, Kavita Y.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.07.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/205/2138; 631/208/68; 631/67/1813/1352; Adult; Aged; Cancer; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Case-Control Studies; Chromosome Mapping; Dermatology; Epidemiology; Female; Genetic Loci; Genetic Predisposition to Disease; Genome, Human; Genome-Wide Association Study; Genomes; Humanities and Social Sciences; Humans; Inheritance Patterns; Male; Melanoma; Meta-analysis; Middle Aged; multidisciplinary; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Pigmentation; Public health; Regression analysis; Science; Science (multidisciplinary); Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; White people; Rhode Island; California; United States > US; Massachusetts
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms12048

Cutaneous squamous cell carcinoma represents the second most common cutaneous malignancy, affecting 7–11% of Caucasians in the United States. The genetic determinants of susceptibility to cutaneous squamous cell carcinoma remain largely unknown. Here we report the results of a two-stage genome-wide association study of cutaneous squamous cell carcinoma, totalling 7,404 cases and 292,076 controls. Eleven loci reached genome-wide significance ( P <5 × 10 −8 ) including seven previously confirmed pigmentation-related loci: MC1R , ASIP , TYR , SLC45A2 , OCA2 , IRF4 and BNC2 . We identify an additional four susceptibility loci: 11q23.3 CADM1 , a metastasis suppressor gene involved in modifying tumour interaction with cell-mediated immunity; 2p22.3; 7p21.1 AHR , the dioxin receptor involved in anti-apoptotic pathways and melanoma progression; and 9q34.3 SEC16A , a putative oncogene with roles in secretion and cellular proliferation. These susceptibility loci provide deeper insight into the pathogenesis of squamous cell carcinoma. Cutaneous squamous cell carcinoma is the second most common type of skin cancer. In this genome-wide association study, which includes over 7,000 cases, the authors identify 4 new susceptibility loci for this cancer and also provide independent replication of 9 previously reported susceptibility loci.