HLA-DRB1 alleles and cervical cancer: A meta-analysis of 36 case-control studies

Abstract

Background: Human leukocyte antigens (HLA) are encoded by closely linked genetic loci, and are important in cervical carcinogenesis. The association between HLA-DRB1 alleles with cervical cancer has been studied extensively, but results reported thus far have been inconsistent. Hence, we performed a meta-analysis to precisely assess this association.

Methods: A literature search was conducted in various online databases to identify suitable articles. Case-control studies investigating the association between HLA-DRB1 alleles and cervical cancer were included in this study. Fixed and random-effect models were used to calculate the pooled odds ratio (OR) and 95% confidence intervals (CIs).

Results: A total of 6645 cases and 9095 controls from 36 case-control studies were included. Of the 13 HLA-DRB1 family alleles, DRB1*09 (OR = 1.30) and DRB1 *15 (OR = 1.60) were associated with cervical cancer risk, whilst DRB1*13 (OR = 0.66) exerted a protective effect. Among the 44 HLA-DRB1 specific alleles, DRB1*04:01 (OR = 1.25), DRB1*10:01 (OR = 1.45), DRB1*11:01 (OR = 1.32), DRB1*15:01 (OR = 1.21) and DRB1*15:02 (OR = 1.55) were associated with an increased risk of cervical cancer. However, DRB1*04:06 (OR = 0.52), DRB1*12:02 (OR = 0.61), DRB1*13:01 (OR = 0.62), DRB1*13:02 (OR = 0.57), and DRB1*14:04 (OR = 0.37) were associated with a decreased risk of cervical cancer. Subgroup analysis also revealed that HLA-DRB1 alleles are associated with cervical cancer in Asian, Caucasian, Hispanic or Latin American and black sub-Saharan Africa populations.

Conclusion: Our meta-analysis revealed that multiple HLA-DRB1 alleles are associated with cervical cancer in women of diverse ancestry populations.

Keywords: Cervical cancer; Genetics; HLA-DRB1; Meta-analysis; Polymorphism.