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Cross-Cancer Pleiotropic Associations with Lung Cancer Risk in African Americans.

Carissa C Jones1,2, Yuki Bradford3, Christopher I Amos4

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Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
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PubMed
Summary
This summary is machine-generated.

This study identified novel genetic associations for lung cancer risk in African Americans. These findings highlight potential shared biological pathways across different cancer types in diverse populations.

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Area of Science:

  • Genetics
  • Cancer Epidemiology
  • Genomic Association Studies

Background:

  • Pleiotropic genetic variants can reveal shared biological pathways across multiple cancers.
  • Previous studies predominantly focused on European-descent populations, potentially missing population-specific associations.
  • This research addresses the gap by examining cross-cancer pleiotropic associations with lung cancer risk specifically in African Americans.

Purpose of the Study:

  • To identify novel genetic variants associated with lung cancer risk in African Americans.
  • To explore cross-cancer pleiotropic associations within this underrepresented population.
  • To uncover shared biological mechanisms contributing to lung cancer development.

Main Methods:

  • A pleiotropic analysis was conducted on 1,410 African American lung cancer cases and 2,843 controls.
  • 36,958 genetic variants previously linked to cancer were examined.
  • Logistic regression models adjusted for key covariates including age, sex, global ancestry, study site, and smoking status.

Main Results:

  • Three novel genomic regions on chromosomes 5q14.3, 16q22.2, and 17q12 were significantly associated with lung cancer risk (FDR-corrected P <0.10).
  • Variant rs7186207 on 16q22.2 showed association with reduced lung cancer risk and modifies DHODH gene expression.
  • Variants rs336958 (5q14.3) and rs11658063 (17q12) were associated with increased and reduced lung cancer risk, respectively.

Conclusions:

  • Novel cross-cancer pleiotropic associations with lung cancer risk were identified in African Americans.
  • These associations involve genes HNF1B, DHODH, and HAPLN1, previously implicated in various cancers.
  • This study is the first to investigate cross-cancer pleiotropic associations for lung cancer in the African American population.