Abstract 766: A genome-wide association study identifies the association of common variants in the major histocompatibility complex with cervical cancer in black South African women

Abstract

Abstract Cervical cancer is the second most common female gynaecological malignancy in sub-Saharan Africa (SSA). Previous genome-wide association studies (GWASs) identified genetic variants associated with cervical cancer in women of European and Asian ancestry, particularly within the major histocompatibility complex (MHC). However, owing to the complexity of linkage disequilibrium and varied environmental exposures in different ancestral populations, regional GWASs are needed to investigate the genetic contribution to the pathogenesis of cervical cancer in continental African populations. A total of 1,637 cervical cancer patients and 761 controls in women of African ancestry were identified from the Johannesburg Cancer Study and the AWI-Gen study, respectively. DNA samples were genotyped on the 2.3 million H3Africa GWAS SNP array and genotyped SNPs imputed to a total of 13,937,308 SNPs. The association between genetic variants and cervical cancer was tested using linear mixed models, adjusting for five principal components and cryptic relatedness. We identified one locus within the MHC region associated with cervical cancer at genome-wide significance, led by rs3129965 (odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.87-0.92, P = 2.292 x 10-11) near HLA-DRA. Four other loci were strongly associated with cervical cancer (P<5x10-7), including rs575105445 (OR=0.77, 95%CI=0.70-0.85, P = 2.188 x 10-07) near HLA-C,rs184053148 (OR =0.79, 95% CI = 0.72-0.86, P = 4.19 x 10-07) in TRIM31,rs12496921 (OR=0.88, 95%CI = 0.84-0.92, P = 1.32 x 10-07) in ROPN1B and rs114031308 (OR= 1.27, 95% CI =1.16-1.39, P =3.06 x 10-07) near TTC26. The genes in these loci are implicated in numerous pathways including antiviral immunity, DNA repair, the regulation of p53, apoptosis, cell growth and differentiation. These discoveries demonstrate the important contribution of common genetic variants to cervical cancer susceptibility and provide insights into its pathogenesis in women of African ancestry. Citation Format: Abram Bunya Kamiza, Wenlong Carl Chen, Jean-Tristan Brandenberg, Michele Ramsay, Christopher G. Mathew. A genome-wide association study identifies the association of common variants in the major histocompatibility complex with cervical cancer in black South African women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 766.