Native American Ancestry Affects the Risk for Gene Methylation in the Lungs of Hispanic Smokers From New Mexico

Am J Respir Crit Care Med. 2013 Nov 1;188(9):1110-6. doi: 10.1164/rccm.201305-0925OC.

Abstract

Rationale: Gene promoter methylation detected in sputum predicts lung cancer risk in smokers. Compared with non-Hispanic whites (NHW), Hispanics have a lower age-standardized incidence for lung cancer.

Objectives: This study compared the methylation prevalence in sputum of NHWs with Hispanics using the Lovelace Smokers cohort (n = 1998) and evaluated the effect of Native American ancestry (NAA) and diet on biomarkers for lung cancer risk.

Methods: Genetic ancestry was estimated using 48 ancestry markers. Diet was assessed by the Harvard University Dietary Assessment questionnaire. Methylation of 12 genes was measured in sputum using methylation-specific polymerase chain reaction. The association between NAA and risk for methylation was assessed using generalized estimating equations. The ethnic difference in the association between pack-years and risk for lung cancer was assessed in the New Mexico lung cancer study.

Measurements and main results: Overall Hispanics had a significantly increased risk for methylation across the 12 genes analyzed (odds ratio, 1.18; P = 0.007). However, the risk was reduced by 32% (P = 0.032) in Hispanics with high versus low NAA. In the New Mexico lung cancer study, Hispanic non-small cell lung cancer cases have significantly lower pack-years than NHW counterparts (P = 0.007). Furthermore, compared with NHW smokers, Hispanic smokers had a more rapidly increasing risk for lung cancer as a function of pack-years (P = 0.058).

Conclusions: NAA may be an important risk modifier for methylation in Hispanic smokers. Smoking intensity may have a greater impact on risk for lung cancer in Hispanics compared with NHWs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • American Native Continental Ancestry Group / genetics*
  • Carcinoma, Non-Small-Cell Lung / ethnology*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Cohort Studies
  • DNA Methylation / physiology*
  • Diet*
  • Female
  • Folic Acid / physiology
  • Hispanic Americans / genetics*
  • Humans
  • Longitudinal Studies
  • Lung Neoplasms / ethnology*
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Multivariate Analysis
  • New Mexico
  • Promoter Regions, Genetic / physiology
  • Risk Factors
  • Smoking / ethnology*
  • Smoking / genetics
  • Sputum / chemistry

Substances

  • Folic Acid