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Investigating multiple candidate genes and nutrients in the folate metabolism pathway to detect genetic and nutritional risk factors for lung cancer.


ABSTRACT:

Purpose

Folate metabolism, with its importance to DNA repair, provides a promising region for genetic investigation of lung cancer risk. This project investigates genes (MTHFR, MTR, MTRR, CBS, SHMT1, TYMS), folate metabolism related nutrients (B vitamins, methionine, choline, and betaine) and their gene-nutrient interactions.

Methods

We analyzed 115 tag single nucleotide polymorphisms (SNPs) and 15 nutrients from 1239 and 1692 non-Hispanic white, histologically-confirmed lung cancer cases and controls, respectively, using stochastic search variable selection (a Bayesian model averaging approach). Analyses were stratified by current, former, and never smoking status.

Results

Rs6893114 in MTRR (odds ratio [OR]?=?2.10; 95% credible interval [CI]: 1.20-3.48) and alcohol (drinkers vs. non-drinkers, OR?=?0.48; 95% CI: 0.26-0.84) were associated with lung cancer risk in current smokers. Rs13170530 in MTRR (OR?=?1.70; 95% CI: 1.10-2.87) and two SNP*nutrient interactions [betaine*rs2658161 (OR?=?0.42; 95% CI: 0.19-0.88) and betaine*rs16948305 (OR?=?0.54; 95% CI: 0.30-0.91)] were associated with lung cancer risk in former smokers. SNPs in MTRR (rs13162612; OR?=?0.25; 95% CI: 0.11-0.58; rs10512948; OR?=?0.61; 95% CI: 0.41-0.90; rs2924471; OR?=?3.31; 95% CI: 1.66-6.59), and MTHFR (rs9651118; OR?=?0.63; 95% CI: 0.43-0.95) and three SNP*nutrient interactions (choline*rs10475407; OR?=?1.62; 95% CI: 1.11-2.42; choline*rs11134290; OR?=?0.51; 95% CI: 0.27-0.92; and riboflavin*rs8767412; OR?=?0.40; 95% CI: 0.15-0.95) were associated with lung cancer risk in never smokers.

Conclusions

This study identified possible nutrient and genetic factors related to folate metabolism associated with lung cancer risk, which could potentially lead to nutritional interventions tailored by smoking status to reduce lung cancer risk.

SUBMITTER: Swartz MD 

PROVIDER: S-EPMC3553105 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Investigating multiple candidate genes and nutrients in the folate metabolism pathway to detect genetic and nutritional risk factors for lung cancer.

Swartz Michael D MD   Peterson Christine B CB   Lupo Philip J PJ   Wu Xifeng X   Forman Michele R MR   Spitz Margaret R MR   Hernandez Ladia M LM   Vannucci Marina M   Shete Sanjay S  

PloS one 20130123 1


<h4>Purpose</h4>Folate metabolism, with its importance to DNA repair, provides a promising region for genetic investigation of lung cancer risk. This project investigates genes (MTHFR, MTR, MTRR, CBS, SHMT1, TYMS), folate metabolism related nutrients (B vitamins, methionine, choline, and betaine) and their gene-nutrient interactions.<h4>Methods</h4>We analyzed 115 tag single nucleotide polymorphisms (SNPs) and 15 nutrients from 1239 and 1692 non-Hispanic white, histologically-confirmed lung canc  ...[more]

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