Miniatura

Fitxers

846881.pdf (1.29 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2023-10-24

Llicència de publicació

cc-by (c) Tsai, Y-Y. et al., 2023
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/208511

Heterozygote advantage at HLA class I and II loci and reduced risk of colorectal cancer

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.3389/fimmu.2023.1268117

Resum

Objective: Reduced diversity at Human Leukocyte Antigen (HLA) loci may adversely affect the host's ability to recognize tumor neoantigens and subsequently increase disease burden. We hypothesized that increased heterozygosity at HLA loci is associated with a reduced risk of developing colorectal cancer (CRC). Methods: We imputed HLA class I and II four-digit alleles using genotype data from a population-based study of 5,406 cases and 4,635 controls from the Molecular Epidemiology of Colorectal Cancer Study (MECC). Heterozygosity at each HLA locus and the number of heterozygous genotypes at HLA class -I (A, B, and C) and HLA class -II loci (DQB1, DRB1, and DPB1) were quantified. Logistic regression analysis was used to estimate the risk of CRC associated with HLA heterozygosity. Individuals with homozygous genotypes for all loci served as the reference category, and the analyses were adjusted for sex, age, genotyping platform, and ancestry. Further, we investigated associations between HLA diversity and tumor-associated T cell repertoire features, as measured by tumor infiltrating lymphocytes (TILs; N=2,839) and immunosequencing (N=2,357). Results: Individuals with all heterozygous genotypes at all three class I genes had a reduced odds of CRC (OR: 0.74; 95% CI: 0.56-0.97, p= 0.031). A similar association was observed for class II loci, with an OR of 0.75 (95% CI: 0.60-0.95, p= 0.016). For class-I and class-II combined, individuals with all heterozygous genotypes had significantly lower odds of developing CRC (OR: 0.66, 95% CI: 0.49-0.87, p= 0.004) than those with 0 or one heterozygous genotype. HLA class I and/or II diversity was associated with higher T cell receptor (TCR) abundance and lower TCR clonality, but results were not statistically significant. Conclusion: Our findings support a heterozygote advantage for the HLA class-I and -II loci, indicating an important role for HLA genetic variability in the etiology of CRC.

Matèries

Càncer colorectal, Antígens CD, Genètica

Matèries (anglès)

Colorectal cancer, CD antigens, Genetics

Citació

Col·leccions

Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

TSAI, Ya-yu, QU, Chenxu, BONNER, Joseph d., SANZ PAMPLONA, Rebeca, LINDSEY, Sidney s., MELAS, Marilena, MCDONNELL, Kevin j., IDOS, Gregory e., WALKER, Christopher p., TSANG, Kevin k., DA SILVA, Diane m., MORATALLA NAVARRO, Ferran, MAOZ, Asaf, RENNERT, Hedy s., KAST, W. martin, GREENSON, Joel k., MORENO AGUADO, Víctor, RENNERT, Gad, GRUBER, Stephen b., SCHMIT, Stephanie l.. Heterozygote advantage at HLA class I and II loci and reduced risk of colorectal cancer. _Frontiers in Immunology_. 2023. Vol. 14. [consulta: 23 de gener de 2026]. ISSN: 1664-3224. [Disponible a: https://hdl.handle.net/2445/208511]

Exportar metadades

JSON - METS

Compartir registre