Genetic susceptibility to cervical squamous cell carcinoma is associated with HLA-DPB1 polymorphisms in Taiwanese women

Abstract

Cervical cancer is a multifactorial disease, and increasing evidence suggests that host immunogenetic background may contribute to its pathogenesis. Genetic variations in human leukocyte antigen (HLA) genes may alter the efficiency of immune response to human papillomavirus (HPV) antigens and have been implicated in the risk of cervical cancer. We investigated whether polymorphisms in the HLA-DPB1 gene were associated with cervical cancer risk in a Taiwanese population. HLA-DPB1 alleles and +550 G/A polymorphism were genotyped in a case-control study of 473 women with cervical squamous cell carcinoma (CSCC) and 676 healthy controls. The presence and genotypes of HPV in CSCC were determined. We found that the DPB1*05:01 and +550 A alleles were associated with decreased and increased risk of CSCC, respectively [odds ratio (OR) = 0.72, Pc = 0.001; OR = 1.25, Pc = 0.03]. In subgroup analysis based on HPV type 16 positivity, significant associations were shown in the DPB1*05:01 and *13:01 alleles (OR = 0.65, Pc = 0.0007; OR = 1.83, Pc = 0.004). Furthermore, the DPB1*05:01-G and *13:01-G haplotypes conferred decreased and increased risk of both CSCC and HPV-16 positive CSCC women, respectively (OR = 0.72, Pc = 0.0009; OR = 0.63, Pc = 0.0004 for DPB1*05:01-G; OR = 1.55, Pc = 0.03; OR = 1.84, Pc = 0.004 for DPB1*13:01-G). A risk haplotype DPB1*02:01-A was also observed in the HPV-16 positive CSCC women (OR = 1.51, Pc = 0.05). These findings suggest that HLA-DPB1 gene is involved in the CSCC development.

Diagnostic and prognostic biomarkers of Human Leukocyte Antigen complex for hepatitis B virus-related hepatocellular carcinoma

“…Hu et al reported, for the first time, that genetic variants in the HLA-DP/DQ loci might be marker polymorphisms for both HBV infection and risk of developing HCC 44. HLA-DPB1 polymorphisms increased the risk for cervical squamous cell carcinoma in Taiwanese women 45.…”

A significant association between rs8067378 at 17q12 and invasive cervical cancer originally identified by a genome-wide association study in Han Chinese is replicated in a Japanese population

“…We also investigated whether HLA-DPB1 alleles are associated with cervical cancer risk in the Japanese population, because this association was found to be significant in Chinese and Taiwanese populations. [12][13][14] …”

A four-DNA methylation signature as a novel prognostic biomarker for survival of patients with gastric cancer

“…The biological involvement of HLA-DPB is mainly in the immune response. HLA-DP is participates in the origin and development of cervical cancer, and different HLA-DP polymorphisms correspond to different cervical cancer risks in the Chinese and Swedish populations [51]. Genetic polymorphism of HLA-DP is also associated with the prognosis of Hodgkin's lymphoma [52].…”