title: Genome-wide association study identifies novel alleles associated with risk of cutaneous basal cell carcinoma and squamous cell carcinoma.
abstract: We conducted a genome-wide association study on cutaneous basal cell carcinoma (BCC) among 2045 cases and 6013 controls of European ancestry, with follow-up replication in 1426 cases and 4845 controls. A non-synonymous SNP in the MC1R gene (rs1805007 encoding Arg151Cys substitution), a previously well-documented pigmentation gene, showed the strongest association with BCC risk in the discovery set (rs1805007[T]: OR (95% CI) for combined discovery set and replication set [1.55 (1.45-1.66); P= 4.3 × 10(-17)]. We identified that an SNP rs12210050 at 6p25 near the EXOC2 gene was associated with an increased risk of BCC [rs12210050[T]: combined OR (95% CI), 1.24 (1.17-1.31); P= 9.9 × 10(-10)]. In the locus on 13q32 near the UBAC2 gene encoding ubiquitin-associated domain-containing protein 2, we also identified a variant conferring susceptibility to BCC [rs7335046 [G]; combined OR (95% CI), 1.26 (1.18-1.34); P= 2.9 × 10(-8)]. We further evaluated the associations of these two novel SNPs (rs12210050 and rs7335046) with squamous cell carcinoma (SCC) risk as well as melanoma risk. We found that both variants, rs12210050[T] [OR (95% CI), 1.35 (1.16-1.57); P= 7.6 × 10(-5)] and rs7335046 [G] [OR (95% CI), 1.21 (1.02-1.44); P= 0.03], were associated with an increased risk of SCC. These two variants were not associated with melanoma risk. We conclude that 6p25 and 13q32 are novel loci conferring susceptibility to non-melanoma skin cancer.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Nan
authors.forename: Mousheng
authors.initials: M
authors.lastname: Xu
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Abrar A
authors.initials: AA
authors.lastname: Qureshi
authors.forename: Constance
authors.initials: C
authors.lastname: Chen
authors.forename: Qun
authors.initials: Q
authors.lastname: Guo
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Gary
authors.initials: G
authors.lastname: Curhan
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002280:Basal Cell Carcinoma / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012878:Skin Neoplasms / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult