ArticleCancer medicine2014
A cis-eQTL of HLA-DRB1 and a frameshift mutation of MICA contribute to the pattern of association of HLA alleles with cervical cancer.
Article in Cancer medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 21 citations in OpenAlex.
- Evidence of the association between asthma and lung cancer risk from mendelian randomization analysis.Scientific reports · 2024Article
- Genomic Risk Factors for Cervical Cancer.Cancers · 2021Review
- Polymorphic variants INSIG2 rs6726538, HLA-DRB1 rs9272143, and GCNT1P5 rs7780883 contribute to the susceptibility of cervical cancer in the Bangladeshi women.Cancer medicine · 2021Article
- Nongenic cancer-risk SNPs affect oncogenes, tumour-suppressor genes, and immune function.British journal of cancer · 2020Article
- Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women.Gynecologic oncology · 2019Article
- Pandemrix-induced narcolepsy is associated with genes related to immunity and neuronal survival.EBioMedicine · 2019Article
- Association of HLA-DRB1, HLA-DQB1 Polymorphisms with HPV 16 E6 Variants among Young Cervical Cancer Patients in China.Journal of Cancer · 2017Article
- The correlation between HLA-DRB1 and HLA-DQB1 gene polymorphisms and cytokines in HPV16 infected women with advanced cervical cancer.International journal of clinical and experimental medicine · 2015Article
- Article
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2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The association of classic human leukocyte antigen (HLA) alleles with risk of cervical cancer has been extensively studied, and a protective effect has consistently been found for DRB1*1301, DQA1*0103, and/or DQB1*0603 (these three alleles are in perfect linkage disequilibrium [LD] and often occur on the same haplotype in Europeans), while reports have differed widely with respect to the effect of HLA-B*07, DRB1*1501, and/or DQB1*0602 (the last two alleles are also in perfect LD in Europeans). It is not clear whether the reported HLA alleles are responsible for the differences in cervical cancer susceptibility, or if functional variants at other locations within the major histocompatibility complex (MHC) region may explain the effect. In order to assess the relative contribution of both classic HLA alleles and single-nucleotide polymorphisms (SNPs) within the MHC region to cervical cancer susceptibility, we have imputed classic HLA alleles in 1034 cervical cancer patients and 3948 controls in a Swedish population for an integrated analysis. We found that the protective haplotype DRB1*1301-DQA1*0103-DQB1*0603 has a direct effect on cervical cancer and always occurs together with the C allele of a HLA-DRB1 cis-eQTL (rs9272143), which increases the expression of HLA-DRB1. The haplotype rs9272143C-DRB1*1301-DQA1*0103-DQB1*0603 conferred the strongest protection against cervical cancer (odds ratio [OR] = 0.41, 95% confidence interval [CI] = 0.32-0.52, P = 6.2 × 10(-13)). On the other hand, the associations with HLA-B*0702 and DRB1*1501-DQB1*0602 are attributable to the joint effects of both the HLA-DRB1 cis-eQTL (rs9272143) and a frameshift mutation (G inserion of rs67841474, also known as A5.1) of the MHC class I polypeptide-related sequence A gene (MICA). Variation in LD between the classic HLA loci, rs9272143 and rs67841474 between populations may explain the different associations of HLA-B*07 and DRB1*1501-DQB1*0602 with cervical cancer between studies. The mechanism suggested may also explain similar inconsistent results for other HLA-associated diseases.
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