Abstract
To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide association study of 38.5 million single nucleotide polymorphisms (SNPs) and small indels identified through whole-genome sequencing of 2230 Icelanders. We imputed genotypes for 4208 BCC patients and 109 408 controls using Illumina SNP chip typing data, carried out association tests and replicated the findings in independent population samples. We found new BCC susceptibility loci at TGM3 (rs214782[G], P = 5.5 × 10−17, OR = 1.29) and RGS22 (rs7006527[C], P = 8.7 × 10−13, OR = 0.77). TGM3 encodes transglutaminase type 3, which plays a key role in production of the cornified envelope during epidermal differentiation.
Highlights
Cutaneous basal cell carcinoma (BCC) is the most common cancer of humans
We first examined BCC susceptibility loci that we had previously identified in GWAS studies, in order to validate our approach and to gain further evidence for the published associations
We noted that two variants, in TGM3 and RGS22, which had been observed at suggestive levels of significance in our previous analysis [8], achieved the Bonferroni-adjusted level of genome-wide significance
Summary
Cutaneous basal cell carcinoma (BCC) is the most common cancer of humans. While it is rarely metastatic, it can be locally invasive and can cause considerable morbidity and economic burden [1]. In common with other forms of skin cancer, the most significant environmental risk factor is UV exposure, but both high- and low-penetrance sequence variants . 3046 Human Molecular Genetics, 2014, Vol 23, No 11 affect risk (2 – 8). The way in which some other variants act to promote BCC susceptibility is more obscure
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