New common variants affecting susceptibility to basal cell carcinoma

• Published in: Nature genetics Vol. 41; no. 8; pp. 909 - 914
• Main Authors: Gudjonsson, Sigurjon A, Sigurdsson, Asgeir, Bonenkamp, Johannes J, Magnusdottir, Droplaug N, Thorisdottir, Kristin, Masson, Gisli, Juberias, Pablo, Rodolfo, Monica, Frigge, Michael L, Nelson, Heather H, Hansson, Johan, Saemundsdottir, Jona, Pehamberger, Hubert, Stacey, Simon N, Corredera, Cristina, Sigurgeirsson, Bardur, Gurzau, Eugene, Nagore, Eduardo, Gulcher, Jeffrey R, Gudmundsson, Julius, Benediktsdottir, Kristrun R, Höiom, Veronica, Thorsteinsdottir, Unnur, Fuentelsaz, Victoria, Saez, Berta, Mayordomo, José I, Thorleifsson, Gudmar, Wendt, Judith, Hochleitner, Pia, Kong, Augustine, Jakobsdottir, Margret, Soriano, Virtudes, Olafsson, Jon H, Stefansson, Kari, Rivoltini, Licia, Santinami, Mario, Aben, Katja K H, Karagas, Margaret R, Maurichi, Andrea, Blondal, Thorarinn, Botella-Estrada, Rafael, Gilaberte, Yolanda, Rudnai, Peter, Grasa, Matilde, van Rossum, Michelle M, Okamoto, Ichiro, Hemminki, Kari, Gudbjartsson, Daniel F, Holm, Hilma, Gretarsdottir, Solveig, Ragnarsson, Rafn, Kumar, Rajiv, Di Mauro, Maria G, Kiemeney, Lambertus A, Rafnar, Thorunn, Koppova, Kvetoslava, Lindblom, Annika, de Vries, Esther, Bjarnason, Hjördis, Kristjansson, Kristleifur, Bjornsdottir, Gyda, Sulem, Patrick, Steinthorsdottir, Valgerdur, Scherer, Dominique
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2009; Nature Publishing Group
• Subjects: Agriculture; Animal Genetics and Genomics; Basal cell carcinoma; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Carcinoma, Basal Cell - complications; Carcinoma, Basal Cell - genetics; Carcinoma, Squamous Cell - genetics; Cells; Chromosomes, Human, Pair 7 - genetics; Chromosomes, Human, Pair 9 - genetics; Coronary Artery Disease - complications; Coronary Artery Disease - genetics; Cyclin-dependent kinases; Dermatology; Disease susceptibility; Environmental health; Fundamental and applied biological sciences. Psychology; Gene Function; Genetic aspects; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Health aspects; Human Genetics; Humans; Keratin; Keratin-5 - genetics; letter; Linkage Disequilibrium - genetics; Medical sciences; Medicin och hälsovetenskap; Melanoma; Melanoma - pathology; Membrane Proteins - genetics; Molecular Sequence Data; Multivariate analysis; Neoplasm Proteins - genetics; Pigmentation; Polymorphism, Single Nucleotide - genetics; Risk factors; Sample size; Single nucleotide polymorphisms; Skin Neoplasms - complications; Skin Neoplasms - genetics; Tumors of the skin and soft tissue. Premalignant lesions; Ultraviolet radiation; Sweden; Spain; Variant; Skin disease; Basal cell carcinoma; Malignant tumor; Cancer
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.412

In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 × 10−9). A variant at 9p21 near CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P = 6.9 × 10−9), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR = 1.23, P = 5.7 × 10−10). The effect of rs157935[T] is dependent on the parental origin of the risk allele. None of these variants were found to be associated with melanoma or fair-pigmentation traits. A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. Finally, we report conclusive evidence that rs401681[C] in the TERT-CLPTM1L locus confers susceptibility to BCC but protects against melanoma.