A DRD1 polymorphism predisposes to lung cancer among those exposed to secondhand smoke during childhood

Ana I. Robles, Ping Yang, Jin Jen, Andrew C. McClary, Kara Calhoun, Elise D. Bowman, Kirsi Vähäkangas, K. Leigh Greathouse, Yi Wang, Susan Olivo-Marston, Angela S. Wenzlaff, Bo Deng, Ann G. Schwartz, Bríd M. Ryan

Research output: Contribution to journalArticlepeer-review

Abstract

Lung cancer has a familial component which suggests a genetic contribution to its etiology. Given the strong evidence linking smoking with lung cancer, we studied miRNA-related loci in genes associated with smoking behavior. CHRNA, CHRNB gene families, CYP2A6, and DRD1 (dopamine receptor D1) were mined for SNPs that fell within the seed region of miRNA binding sites and then tested for associations with risk in a three-stage validation approach. A 3'UTR (untranslated region) SNP in DRD1 was associated with a lower risk of lung cancer among individuals exposed to secondhand smoke during childhood [OR, 0.69; 95% confidence interval (CI), 0.60-0.79; P <0.0001]. This relationship was evident in both ever (OR, 0.74; 95% CI, 0.62-0.88; P = 0.001) and never smokers (OR, 0.61; 95% CI, 0.47-0.79; P <0.0001), European American (OR, 0.65; 95% CI, 0.53-0.80; P <0.0001), and African American (OR, 0.73; 95% CI, 0.62-0.88; P = 0.001) populations. Although much remains undefined about the long-term risks associated with exposure to secondhand smoke and heterogeneity between individuals in regard to their susceptibility to the effects of secondhand smoke, our data show an interaction between an SNP in the 3'UTR of DRD1 and exposure to secondhand smoke during childhood. Further work is needed to explore the mechanistic underpinnings of this SNP and the nature of the interaction between DRD1 and exposure to secondhand smoke during childhood.

Original languageEnglish (US)
Pages (from-to)1210-1218
Number of pages9
JournalCancer Prevention Research
Volume7
Issue number12
DOIs
StatePublished - Dec 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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