Genetic variants in the HLA class II region associated with risk of cutaneous squamous cell carcinoma

Cancer Immunology, Immunotherapy : CII
Wei WangMaryam M Asgari

Abstract

The immune system has been implicated in the pathophysiology of cutaneous squamous cell carcinoma (cSCC) as evidenced by the substantially increased risk of cSCC in immunosuppressed individuals. Associations between cSCC risk and single nucleotide polymorphisms (SNPs) in the HLA region have been identified by genome-wide association studies (GWAS). The translation of the associated HLA SNPs to structural amino acids changes in HLA molecules has not been previously elucidated. Using data from a GWAS that included 7238 cSCC cases and 56,961 controls of non-Hispanic white ancestry, we imputed classical alleles and corresponding amino acid changes in HLA genes. Logistic regression models were used to examine associations between cSCC risk and genotyped or imputed SNPs, classical HLA alleles, and amino acid changes. Among the genotyped SNPs, cSCC risk was associated with rs28535317 (OR = 1.20, p = 9.88 × 10- 11) corresponding to an amino-acid change from phenylalanine to leucine at codon 26 of HLA-DRB1 (OR = 1.17, p = 2.48 × 10- 10). An additional independent association was observed for a threonine to isoleucine change at codon 107 of HLA-DQA1 (OR = 1.14, p = 2.34 × 10- 9). Among the classical HLA alleles, cSCC was associated with ...Continue Reading

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Citations

Apr 27, 2019·International Journal of Molecular Sciences·Matthew J BottomleyIrene Leigh
Dec 14, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Priyadharsini NagarajanAmanda Ewart Toland
Nov 2, 2019·The Journal of Investigative Dermatology·Yuhree KimMaryam M Asgari

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