title: Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Harvind S
authors.initials: HS
authors.lastname: Chahal
authors.affiliation: Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin &Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana 46202, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Ransohoff
authors.affiliation: 23andMe Inc., Mountain View, California 94041, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hinds
authors.affiliation: Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin &Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana 46202, USA.
authors.forename: Wenting
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin &Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana 46202, USA.|Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital and Institute, National Clinical Research Center for Cancer, Tianjin &Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Hong-Ji
authors.initials: HJ
authors.lastname: Dai
authors.affiliation: Department of Dermatology, Warren Alpert Medical School, Brown University, Providence, Rhode Island 02903, USA.|Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island 02903, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Abrar A
authors.initials: AA
authors.lastname: Qureshi
authors.affiliation: Department of Dermatology, Warren Alpert Medical School, Brown University, Providence, Rhode Island 02903, USA.|Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island 02903, USA.
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Li
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.|Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Jean Y
authors.initials: JY
authors.lastname: Tang
authors.affiliation: Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin &Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana 46202, USA.|Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital and Institute, National Clinical Research Center for Cancer, Tianjin &Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Kavita Y
authors.initials: KY
authors.lastname: Sarin
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002874:Chromosome Mapping; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins