Genetics of Smoking Behaviors in American Indians

Authors

Collaborative to Improve Native Cancer Outcomes (CINCO), a P50 Center for Population Health and Health Disparities program project sponsored by the National Cancer Institute

Publication Date

11-1-2020

Journal

Cancer Epidemiology, Biomarkers & Prevention

DOI

10.1158/1055-9965.EPI-20-0026

PMID

32855268

PMCID

PMC8597394

PubMedCentral® Posted Date

11-17-2021

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Smoking, Surveys and Questionnaires, Young Adult, American Indian or Alaska Native, genomics; single nucleotide polymorphisms; tobacco dependence; nicotine metabolism; Indians, North American

Abstract

BACKGROUND: The smoking behavior of American Indians (AI) differs from that of non-Hispanic whites (NHW). Typically light smokers, cessation interventions in AIs are generally less effective. To develop more effective cessation programs for AIs, clinicians, researchers, and public health workers need a better understanding of the genetic factors involved in their smoking behavior. Our aim was to assess whether SNPs associated with smoking behavior in NHWs are also associated with smoking in AIs.

METHODS: We collected questionnaire data on smoking behaviors and analyzed blood and saliva samples from two Tribal populations with dramatically different cultures and smoking prevalence, one in the Northern Plains (n=323) and the other in the Southwest (n=176). A total of 384 SNPs were genotyped using an Illumina custom GoldenGate platform. Samples were also assessed for cotinine and 3-hydroxycotinine as markers of nicotine intake and nicotine metabolite ratio.

RESULTS: Among 499 participants, we identified, in the NP sample only, a variant of the gamma-aminobutyric acid receptor subunit alpha-2 (GABRA2) (rs2119767) on chromosome 4p that was associated with many of the intake biomarkers of smoking we examined, suggesting a role for this gene in modifying smoking behavior in this population. We also identified 3 SNPs, in the SW sample only, as significant correlates of only cigarettes per day: rs4274224, rs4245147 (both dopamine receptor D2 gene), and rs1386493 (tryptophan hydroxylase 2 gene).

CONCLUSIONS: The contribution of many genes known to underlie smoking behaviors in NHWs may differ in AIs.

IMPACT: Once validated, these variants could be useful in developing more effective cessation strategies.

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