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
References
Jul 15, 1991·Cancer·D B CzarneckiB Tait
Jan 1, 1988·Dermatologica·D CerimeleG V Campus
Jan 1, 1993·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M T GloverI M Leigh
Apr 25, 2003·The New England Journal of Medicine·Sylvie EuvrardAlain Claudy
Mar 25, 2006·Nature Reviews. Immunology·E Yvonne JonesChristian Siebold
Apr 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Clare Baecher-AllanDavid A Hafler
Dec 30, 2006·PLoS Genetics·Nick PattersonDavid Reich
May 10, 2007·The British Journal of Dermatology·M TrakatelliD Abeni
Aug 9, 2007·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Linda S LindströmKamila Czene
Dec 17, 2008·Annals of the Rheumatic Diseases·A L FeitsmaR E M Toes
Nov 6, 2010·Science·UNKNOWN International HIV Controllers StudyMeng Zhao
Nov 10, 2010·International Immunology·Marcus O ButlerNaoto Hirano
Mar 26, 2011·Science·Robert D SchreiberMark J Smyth
May 14, 2011·Genomics·Thomas J HoffmannNeil Risch
Sep 10, 2011·Genomics·Thomas J HoffmannNeil Risch
Jan 31, 2012·Nature Genetics·Soumya RaychaudhuriPaul I W de Bakker
Jan 8, 2013·Journal of the National Cancer Institute·Michael J SilverbergMaryam M Asgari
Jun 14, 2013·PloS One·Xiaoming JiaPaul I W de Bakker
Jun 28, 2014·Blood·Christian A FernandezMary V Relling
Dec 2, 2014·Epigenetics : Official Journal of the DNA Methylation Society·Jian Ming HuFeng Li
Jan 13, 2015·American Journal of Human Genetics·Hanna M OllilaEmmanuel Mignot
Feb 28, 2015·GigaScience·Christopher C ChangJames J Lee
Mar 31, 2015·Seminars in Cancer Biology·Dass S VinayByoung S Kwon
Jun 21, 2015·Genetics·Mark N KvaleNeil Risch
Jan 7, 2016·European Journal of Human Genetics : EJHG·Eric JorgensonLing Shen
Feb 2, 2016·The Journal of Investigative Dermatology·Maryam M AsgariAlice S Whittemore
Feb 18, 2016·ELife·Prithvi RajEdward K Wakeland
Jul 19, 2016·Nature Communications·Harvind S ChahalKavita Y Sarin
Citations
Jun 23, 2020·Journal of Viral Hepatitis·Yang DengGuangwen Cao
Apr 27, 2019·International Journal of Molecular Sciences·Matthew J BottomleyIrene Leigh
Oct 17, 2018·Nature Communications·Nilah M IoannidisAlice S Whittemore
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