Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits

Abstract

To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 x 10(-12)) and rs801114 on 1q42 (OR = 1.28, P = 5.9 x 10(-12)). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers.

PTEN regulates RPA1 and protects DNA replication forks

“…No Rpa1 −/− mice were obtained, likely due to embryonic lethality. As azoxymethane (AOM) followed by three rounds of dextran sodium sulfate (DSS) [29] exposure produces a well-recognized model which mimics the genomic instability in human CRC [30][31][32], we generated an AOM/DSS-induced CRC model in Rpa1 +/− and Rpa1 +/+ mice in vivo as shown in Figure 5F. According to the AOM/DSS protocol ( Figure 5F), mice were euthanized and evaluated for cancer.…”

Exploratory Investigation of Genetic Associations with Basal Cell Carcinoma Risk: Genome-Wide Association Study in Jeju Island, Korea

“…Using large populations with mostly Caucasian individuals, GWAS have produced sufficient evidence of the genetic associations with BCC risk (Stokowski et al, 2007;Sulem et al, 2007;Brown et al, 2008;Han et al, 2008;Stacey et al, 2008;Sulem et al, 2008;Falchi et , 2009b;Rafnar et al, 2009;Stacey et al, 2009;Duffy et al, 2010). However, a paucity of studies based on data from non-Caucasian deals with the genetic associations with BCC risk (Cho et al, 2001;Kim et al, 2002;Kang et al, 2007).…”

Common variants modify the age of onset for basal cell carcinomas in Gorlin syndrome

“…Nine SNPs, previously published as being associated with increased BCC risk [13][14][15] (rs1805007 chr16.hg19:89919709C4T, rs12210050 chr6.hg19:475489C4T, rs7335046 chr13.hg19:99389484G4C, rs7538876 chr1.hg19:17395867G4A, rs801114 chr1.hg19:228862088G4A, rs401681 chr5.hg19:1321972G4A, rs2151280 chr9.hg19:22034720G4A, rs157935 chr7.hg19:130900794T4G and rs11170164 chr12.hg19:52913668G4T), were genotyped using pre-designed Taqman SNP genotyping allelic discrimination assays (Applied Biosystems, Warrington, UK). SNPs can be found on dbSNP (URL: http://www.ncbi.nlm.nih.gov/SNP/).…”

“…13 An independent GWAS of over 2000 BCC cases of Icelandic and Eastern European origin reported two loci at 1p36 (rs7538876) and 1q42 (rs801114) associated with BCC susceptibility. 14 In a follow-up GWAS of over 3000 BCC cases, by the same group, further variants including keratin 5 (KRT5, rs11170164), and the 9p21 (rs2151280), 7q32 (rs157935) and TERT-CLPTM1L (rs401681) loci were associated with an increased BCC risk. 15 In this study, we genotyped nine variants previously associated with increased BCC risk, in a cohort of individuals with Gorlin syndrome, to assess their effect on the age of BCC onset.…”