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.
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- Stuart Craig
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