Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Journal Sections
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Collections
      • COVID-19 & Cancer Resource Center
      • Precision Medicine and Therapeutic Resistance
      • Clinical Trials
      • Immuno-oncology
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
    • Journal Press Releases
  • COVID-19
  • Webinars
  • 10th Anniversary
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Cancer Discovery
Cancer Discovery
  • Home
  • About
    • The Journal
    • AACR Journals
    • Journal Sections
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Collections
      • COVID-19 & Cancer Resource Center
      • Precision Medicine and Therapeutic Resistance
      • Clinical Trials
      • Immuno-oncology
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
    • Journal Press Releases
  • COVID-19
  • Webinars
  • 10th Anniversary
  • Search More

    Advanced Search

Research Watch

Variants at an HLA and an IL Locus Are Associated with NKTCL

DOI: 10.1158/2159-8290.CD-RW2020-008 Published February 2020
  • Article
  • Info & Metrics
Loading
  • Major Finding: A genome-wide association study identified two risk loci for natural killer T-cell lymphoma (NKTCL).

  • Concept: In vitro experiments implicate class II histone leukocyte antigen and IL18 in NKTCL pathogenesis.

  • Impact: This work genetically pinpoints two susceptibility loci and provides supporting biological evidence.

Extranodal natural killer T-cell lymphoma (NKTCL; nasal type) is known to predominantly affect people of Asian or Latin American descent and has been linked to infection with Epstein-Barr virus (EBV); however, EBV infection is very common in adults, and the genetic basis for the disparity in prevalence among populations is not well established. In one genome-wide association study (GWAS), common variants of HLA-DPB1 were found to be associated with an increased NKTCL risk. In a larger GWAS by the same group involving patients and matched control participants from multiple East Asian populations, Lin, Xu, Chen, Huang, Chen, Song, Chan, Li, and colleagues identified two previously unknown susceptibility loci: IL18RAP and HLA-DRB1. Participants homozygous for all three now-identified risk variants had the greatest risk (18- to 51-fold higher) of developing NKTCL. The fact that both HLA-DPB1 and HLA-DRB1 have now been pinpointed as risk loci for NKTCL implicates the class II histone leukocyte antigen (HLA) in the etiology of NKTCL. Interestingly, IL18RAP, encoding IL18 receptor accessory protein, represents the first known risk locus for NKTCL outside the HLA region. In two NKTCL cell lines, IL18RAP knockdown substantially decreased cell growth and appeared to cause cell-cycle arrest at the G0–G1 and G2–M transitions, suggesting that IL18RAP may mediate proliferation through effects on cell-cycle progression. Although the larger GWAS performed in this study had sufficient statistical power to identify variants with moderate or greater effect sizes, the work has some limitations; specifically, in vivo evidence would add weight to these findings, as would a more detailed molecular characterization of the mechanisms at play in NKTCL pathogenesis potentially driven by these variants. Further, a larger study would be needed to identify risk variants with smaller effect sizes, and research on participants from other populations (e.g., those of European or African descent) is needed. In summary, this study identifies two new susceptibility loci for NKTCL and provides hints about how variants at these loci may promote disease.

Lin GW, Xu C, Chen K, Huang HQ, Chen J, Song B, et al. Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study in multiple populations. Lancet Oncol 2019 Dec 23 [Epub ahead of print].

Notes

Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.

  • ©2020 American Association for Cancer Research.
PreviousNext
Back to top
Cancer Discovery: 10 (2)
February 2020
Volume 10, Issue 2
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Editorial Board (PDF)

Sign up for alerts

View this article with LENS

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Discovery article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Variants at an HLA and an IL Locus Are Associated with NKTCL
(Your Name) has forwarded a page to you from Cancer Discovery
(Your Name) thought you would be interested in this article in Cancer Discovery.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Variants at an HLA and an IL Locus Are Associated with NKTCL
Cancer Discov February 1 2020 (10) (2) OF9; DOI: 10.1158/2159-8290.CD-RW2020-008

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Variants at an HLA and an IL Locus Are Associated with NKTCL
Cancer Discov February 1 2020 (10) (2) OF9; DOI: 10.1158/2159-8290.CD-RW2020-008
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Notes
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Research Watch

  • Cell-Intrinsic Programs Partition Nutrients in Tumor Microenvironment
  • Extrachromosomal DNA Can Promote Oncogene Transcription in Trans
  • Transient Rest Reverses Exhaustion of Chimeric Antigen Receptor T Cells
Show more Research Watch

Genetics

  • Noncanonical Open Reading Frames Produce Functional Proteins in Cancer
  • The Spindle Assembly Checkpoint Is a Vulnerability of Aneuploid Cells
  • Chromothripsis Generates Oncogene-Containing Extrachromosomal DNA
Show more Genetics
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • OnlineFirst
  • Current Issue
  • Past Issues

Info For

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Discovery

  • About the Journal
  • Editors
  • Journal Sections
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Discovery
eISSN: 2159-8290
ISSN: 2159-8274

Advertisement