Affected sib-pair analysis of the contribution of HLA class I and class II loci to development of cervical cancer

Abstract

Cervical cancer is a multifactorial disease and infection by oncogenic human papilloma viruses represents the main environmental risk factor. Only a subset of infections becomes persistent and develops into cancer, implying that genetic susceptibility factors are needed for malignant progression. Here, we use a population-based cohort of affected sib-pairs (ASPs) to examine the role of the human leukocyte antigen (HLA) class I and class II loci in cervical cancer susceptibility. Analysis of 278 ASPs revealed significant excess genetic sharing for all three HLA class II loci studied, DPB1, DQB1 and DRB1, with the strongest evidence for DQB1 and DRB1. No evidence of excess sharing was observed for the HLA class I HLA-B and HLA-A loci. When the material was stratified on the basis of the DQB1*0602/DRB1*1501 susceptibility haplotype, carriers showed significant sharing for all loci, whereas non-carriers showed no evidence of excess genetic sharing at any of the loci. However, for the DPB1 locus there was no difference in allele frequency between carriers and non-carriers indicating that the effect seen in DPB1 is not simply due to linkage disequilibrium. Our results show that the HLA class II represents a major genetic susceptibility locus to cervical cancer in contrary to the class I that do not appear to have a significant impact on predisposition to the disease. The strongest class II effects are coming from the DQB1 and DRB1 loci, but the DPB1 locus also contributes to the susceptibility to cervical cancer.

Human Leukocyte Antigens I and II Haplotypes Associated With Human Papillomavirus 16-Positive Invasive Cervical Cancer in Mexican Women

“…12,29 Several studies have shown some evidence supporting that certain HLA class II alleles or allele combinations could explain higher susceptibility in women with CC. 19,25,30,31 Our findings support previous studies that found the HLA-DR15/DQ*0602 haplotype to be positively associated with cervical neoplasia, 7,25,32 but this is inconsistent with other reports that have suggested a negative association. 33 Haplotypes HLA-B7/DQ*0302, 34 DR11/ DQ*0301, 29 DR4/DQ*0301, and DR1/DQ*0301 30 have been associated with CC susceptibility in Latin-American, Senegalese, and white American women.…”

Genetic polymorphisms of FAS and EVER genes in a Greek population and their susceptibility to cervical cancer: a case control study

“…Cohort 1 was based on a nested study within the Northern Sweden Health and Disease Study Cohort [9]. Cohort 2 included women from families with at least two affected women from all of Sweden [17]. Two of the SNPs studied (rs2290907 and rs16970849) were found to be significantly correlated with cervical cancer (CIN3 and ICC) [16].…”

Human Leukocyte Antigen Class I and II Alleles and Cervical Adenocarcinoma

“…Studies in Scandinavian countries, with well-established population registries, provide evidence for familial aggregation in cervical cancer incidence (and that of its immediate precursor, CIN3) (7–11). Those studies reported that cervical cancer risk associations are strongest for full-relatives, intermediate for half-siblings, and lowest for non-biological relatives.…”