Fine Mapping of the Major Histocompatibility Complex Region and Association of the HLA-B*52:01 Allele With Cervical Cancer in Japanese Women

Masuda, Tatsuo; Ito, Hidemi; Hirata, Jun; Sakaue, Saori; Ueda, Yutaka; Kimura, Tadashi; Takeuchi, Fumihiko; Murakami, Yoshinori; Matsuda, Koichi; Matsuo, Keitaro; Okada, Yukinori

doi:10.1001/jamanetworkopen.2020.23248

Cited by 7 publications

(6 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another study on cross-trait analysis in gynaecological cancers with some overlap with the Japanese Biobank identified two novel cervical cancer variants at INS-IGF2 (rs150806792) and SOX9 (rs140991990), requiring further validation [152]. The most recent Japanese Biobank cervical cancer GWAS did not identify any new variants at GWS, although it confirmed previous findings [120] (Table 1).…”

Section: Other Gwas Loci For Cervical Cancer or Dysplasiasupporting

confidence: 71%

See 1 more Smart Citation

Genomic Risk Factors for Cervical Cancer

Ramachandran

Dörk

2021

Cancers

View full text Add to dashboard Cite

Cervical cancer is the fourth common cancer amongst women worldwide. Infection by high-risk human papilloma virus is necessary in most cases, but not sufficient to develop invasive cervical cancer. Despite a predicted genetic heritability in the range of other gynaecological cancers, only few genomic susceptibility loci have been identified thus far. Various case-control association studies have found corroborative evidence for several independent risk variants at the 6p21.3 locus (HLA), while many reports of associations with variants outside the HLA region remain to be validated in other cohorts. Here, we review cervical cancer susceptibility variants arising from recent genome-wide association studies and meta-analysis in large cohorts and propose 2q14 (PAX8), 17q12 (GSDMB), and 5p15.33 (CLPTM1L) as consistently replicated non-HLA cervical cancer susceptibility loci. We further discuss the available evidence for these loci, knowledge gaps, future perspectives, and the potential impact of these findings on precision medicine strategies to combat cervical cancer.

show abstract

Section: Other Gwas Loci For Cervical Cancer or Dysplasiasupporting

confidence: 71%

“…Even where the causal variants were determined, it still remains a challenge to assign biological function to the variants and identify the causal gene(s). Furthermore, only a handful of results so far has been attempted for fine-mapping or functional validation via chromatin conformation or eQTL analysis [119,128,132,142,152,170].…”

Section: Discussionmentioning

confidence: 99%

Genomic Risk Factors for Cervical Cancer

Ramachandran

Dörk

2021

Cancers

View full text Add to dashboard Cite

show abstract

“…9,10,[12][13][14]16,19,22,37,38 Recently, some GWAS confirmed the previously identified loci at 6p21.3-where the HLA region is located-as associated with CIN III 39 and CC 19,40 in European descent populations and a Chinese population. 41 However, the role of amino acids at specific positions of the HLA peptide-binding cleft was not extensively explored yet, 19,21 and there is no data F I G U R E 4 3D images of the peptide-binding cleft structure of HLA molecules built at the PyMol molecular graphics software, using the crystal structure of HLA-C (PDB ID: 5VGD) 30,31 (A, B) and HLA-DRB1 (PDB ID: 5NI9) 32,33 42 and each group present ancestry components from all of these groups. The average of each ancestry component (Americans, Africans, and Europeans) differs between groups, 42 but intragroup heterogeneity also exists.…”

Section: Discussionmentioning

confidence: 99%

“…Another limitation is our restricted sample size, which limits our statistical power. Nevertheless, considering that few studies have previously investigated the association between amino acid positions of HLA molecules and CIN/CC in the literature, 19,21 we performed an exploratory study aiming to bring new perspectives to the field.…”

Section: Discussionmentioning

confidence: 99%

“…8 As antigen presentation to these cells depends on HLA molecules, and HLA genes are the most polymorphic and polyallelic loci in the human genome, several studies investigated its influence on HPV-related cervical diseases. [9][10][11][12][13][14][15][16][17][18][19] Classical HLA class I and II alleles such as HLA-B*07, 20 HLA-B*52:01, 21 and HLA-DRB1*15 18,22,23 were previously associated with higher CC risk. In contrast, HLA-DRB1*13 was associated with disease protection 10,20,24 in different populations.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inside the pocket: Critical elements of HLA‐mediated susceptibility to cervical precancerous lesions

Gonçalves

França

Xavier

et al. 2021

HLA

View full text Add to dashboard Cite

Human papillomavirus (HPV) infection is a necessary cause for cervical cancer (CC), but it also depends on genetic factors, such as HLA polymorphism. However, few reports addressed the role of amino acids residues at the HLA peptide-binding cleft in HPV-related cervical disease. Therefore, we aimed to investigate the association between HLA-B, HLA-C, and HLA-DRB1 polymorphism and amino acid residues composing the pockets of the peptide-binding cleft of the respective polypeptide chains with cervical intraepithelial neoplasia (CIN II/III). HLA typing was performed by PCR-SSOP in 184 women with CIN II/III and 174 controls from South Brazil. Associations were estimated by multivariate logistic regression. FDR test was performed to correct the p-value for multiple comparisons. HLA-DRB1*13:01 was associated with protection against CIN II/III, while HLA-C*03:04 was associated with susceptibility. The amino acid residues isoleucine, tyrosine, and leucine at positions 95, 116, and 163 of HLA-C, respectively, were associated with CIN II/III susceptibility. In

show abstract

HLA imputation and its application to genetic and molecular fine-mapping of the MHC region in autoimmune diseases

Naito

Okada

2021

Semin Immunopathol

Self Cite

View full text Add to dashboard Cite

Variations of human leukocyte antigen (HLA) genes in the major histocompatibility complex region (MHC) significantly affect the risk of various diseases, especially autoimmune diseases. Fine-mapping of causal variants in this region was challenging due to the difficulty in sequencing and its inapplicability to large cohorts. Thus, HLA imputation, a method to infer HLA types from regional single nucleotide polymorphisms, has been developed and has successfully contributed to MHC fine-mapping of various diseases. Different HLA imputation methods have been developed, each with its own advantages, and recent methods have been improved in terms of accuracy and computational performance. Additionally, advances in HLA reference panels by next-generation sequencing technologies have enabled higher resolution and a more reliable imputation, allowing a finer-grained evaluation of the association between sequence variations and disease risk. Risk-associated variants in the MHC region would affect disease susceptibility through complicated mechanisms including alterations in peripheral responses and central thymic selection of T cells. The cooperation of reliable HLA imputation methods, informative fine-mapping, and experimental validation of the functional significance of MHC variations would be essential for further understanding of the role of the MHC in the immunopathology of autoimmune diseases.

show abstract

Fine Mapping of the Major Histocompatibility Complex Region and Association of the HLA-B*52:01 Allele With Cervical Cancer in Japanese Women

Cited by 7 publications

References 26 publications

Genomic Risk Factors for Cervical Cancer

Genomic Risk Factors for Cervical Cancer

Inside the pocket: Critical elements of HLA‐mediated susceptibility to cervical precancerous lesions

HLA imputation and its application to genetic and molecular fine-mapping of the MHC region in autoimmune diseases

Contact Info

Product

Resources

About