Identification of Susceptibility Loci for Cutaneous Squamous Cell Carcinoma

Abstract

We report a genome-wide association study (GWAS) of cutaneous squamous cell carcinoma (SCC) conducted among non-Hispanic white (NHW) members of the Kaiser Permanente Northern California (KPNC) health care system. The study includes a genome-wide screen of 61,457 members (6,891 cases and 54,566 controls) genotyped on the Affymetrix Axiom European array and a replication phase involving an independent set of 6,410 additional members (810 cases and 5600 controls). Combined analysis of screening and replication phases identified ten loci containing single-nucleotide polymorphisms (SNPs) with P-values < 5×10-8. Six loci contain genes in the pigmentation pathway; SNPs at these loci appear to modulate SCC risk independently of the pigmentation phenotypes. Another locus contains HLA class II genes studied in relation to elevated SCC risk following immunosuppression. SNPs at the remaining three loci include an intronic SNP in FOXP1 at locus 3p13, an intergenic SNP at 3q28 near TP63, and an intergenic SNP at 9p22 near BNC2. These findings provide insights into the genetic factors accounting for inherited SCC susceptibility.

Cutaneous squamous cell cancer (cSCC) risk and the human leukocyte antigen (HLA) system

“…This locus lies 35 kb upstream of HLA-DQB1 , a gene also associated with squamous cell cervical cancer risk [12]. Asgari et al [13] found that HLA locus 6p21 reached genome-wide significance and was strongly associated with cSCC risk. This locus is associated with expression levels of HLA-DQA1 , HLA-DQB1 , and HLA-DRB5 .…”

“…Table 2 includes HLA locus 6p21 identified by Asgari et al [13], as it was strongly associated with cSCC risk and the risk ratio per allele was not seen to vary by immunosuppression status. Table 2 also summarizes a reanalysis by Glover et al in 1993 [6] of the data reported in their 1991 study [14], but with some controls reclassified as cSCC cases upon more detailed screening.…”

A GWAS of Cutaneous Squamous Cell Carcinoma—Letter

“…Here we report a comparison of these results with those of a previous GWAS involving 7,701 non-Hispanic White (NHW) cSCC patients and 60,186 NHW control subjects in the Kaiser Permanente Northern California (KPNC) health care system (2). …”

Prevalência e diversidade de beta-papilomavírus em amostras anogenitais e orais de homens do estudo HIM

“…Homens residentes no EUA (OR = 0,55, 95% intervalo de confiança [IC] de 0,38-0,80) e Brasil (OR = 0,49, 95% CI 0, 73) foram significativamente menos propensos a serem detectados com algum β-HPV no canal anal, comparado aos residentes no México. A idade foi marginalmente associada à maior prevalência de HPV na região do canal anal sendo que de homens mais velhos (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)OR = 1,30,95% CI 0,82;OR = 1,59,95% CI 0,58) foram mais propensos a serem positivos para DNA de β-HPV, comparado a homens mais jovens (18-30 anos). A prevalência de algum β-HPV na cavidade oral também foi significativamente associada ao país de residência e idade.…”

“…Samples were tested for PCR amplification with PGMY09/11 primers, and HPV genotyping was conducted with the Roche Linear Array (Roche Molecular Diagnostics, Alameda, CA, USA), which is able to discriminate 37 α-HPV types (oncogenic types 16,18,31,33,35,39,45,51,52,56,58,59, and 66; non-oncogenic types 6,11,26,40,42,53,54,55,61,62,64,[67][68][69][70][71][72][73][81][82][83][84]IS39,and CP6108) [14]. Samples that tested PCR-positive and Linear Array-negative with all specific HPV probes were considered to be unclassified and included in the present study.…”