Dataset Information

Folate/homocysteine metabolism and lung cancer risk among smokers.

ABSTRACT: BACKGROUND:Folate and homocysteine are involved in DNA synthesis and methylation processes, which are deregulated during carcinogenesis. OBJECTIVES:The aim of this study was to assess the relationship between folate/homocysteine concentrations, the functional polymorphisms of folate/homocysteine genes and lung cancer risk among cigarette smokers. STUDY DESIGN:The study included 132 lung cancer patients and 396 controls from northern Poland, matched by sex, age and smoking status. The median cigarette pack-years of smoking among both cases and controls was 30.0. Serum, red blood cell (RBC) folates and serum homocysteine concentrations were measured. The genotypes in selected polymorphic sites of the MTHFR, CBS, SHMT1, MTHFD1, MTRR, MTR, TYMS DHFR, TCN2, and SLC19A1 genes were determined. All study participants underwent scanning with low-dose computed tomography. RESULTS:Serum folate concentrations above the median (> 17.5 nmol/l among the healthy controls) were associated with an increased lung cancer risk (odds ratio [OR], 1.54, 95% confidence intervals [CI], 1.04-2.29, P = 0.031). An analogous trend was observed when the population was analysed after subdivision according to RBC folate concentrations, that is, above a value of 506.5 nmol/l (OR, 1.53; 95% CI, 0.95-2.47; P = 0.084). Additionally, in a subset of women, an increased risk of lung cancer development was associated with the SLC19A1 c.80AA genotype (c.80AA versus GG OR, 3.14; 95% CI, 1.32-7.46; P = P = 0.010). CONCLUSION:These results suggest that, in the population consisting of heavy smokers, high folate levels add to the cancerogenic effect of smoking.

SUBMITTER: Stanislawska-Sachadyn A

PROVIDER: S-EPMC6445430 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Folate/homocysteine metabolism and lung cancer risk among smokers.

Stanisławska-Sachadyn Anna A Borzyszkowska Joanna J Krzemiński Michał M Janowicz Alicja A Dziadziuszko Rafał R Jassem Jacek J Rzyman Witold W Limon Janusz J

PloS one 20190402 4

<h4>Background</h4>Folate and homocysteine are involved in DNA synthesis and methylation processes, which are deregulated during carcinogenesis.<h4>Objectives</h4>The aim of this study was to assess the relationship between folate/homocysteine concentrations, the functional polymorphisms of folate/homocysteine genes and lung cancer risk among cigarette smokers.<h4>Study design</h4>The study included 132 lung cancer patients and 396 controls from northern Poland, matched by sex, age and smoking s ...[more]

PMID: 30939165

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Project description:BackgroundA low level of methylation at cg05575921 in the aryl-hydrocarbon receptor repressor (AHRR) gene is robustly associated with smoking, and some studies have observed associations between cg05575921 methylation and increased lung cancer risk and mortality. To prospectively examine whether decreased methylation at cg05575921 may identify high risk subpopulations for lung cancer screening among heavy smokers, and mortality in cases, we evaluated associations between cg05575921 methylation and lung cancer risk and mortality, by histotype, in heavy smokers.MethodsThe β-Carotene and Retinol Efficacy Trial (CARET) included enrollees ages 45-69 with ≥ 20 pack-year smoking histories and/or occupational asbestos exposure. A subset of CARET participants had cg05575921 methylation available from HumanMethylationEPIC assays of blood collected on average 4.3 years prior to lung cancer diagnosis in cases. Cg05575921 methylation β-values were treated continuously for a 10% methylation decrease and as quintiles, where quintile 1 (Q1, referent) represents high methylation and Q5, low methylation. We used conditional logistic regression models to examine lung cancer risk overall and by histotype in a nested case-control study including 316 lung cancer cases (diagnosed through 2005) and 316 lung cancer-free controls matched on age (±5 years), sex, race/ethnicity, enrollment year, current/former smoking, asbestos exposure, and follow-up time. Mortality analyses included 372 lung cancer cases diagnosed between 1985 and 2013 with available methylation data. We used Cox proportional hazards models to examine mortality overall and by histotype.ResultsDecreased cg05575921 methylation was strongly associated with smoking, even in our population of heavy smokers. We did not observe associations between decreased pre-diagnosis cg05575921 methylation and increased lung cancer risk, overall or by histotype. We observed linear increasing trends for lung cancer-specific mortality across decreasing cg05575921 methylation quintiles for adenocarcinoma and small cell carcinoma (P-trends = 0.01 and 0.04, respectively).ConclusionsIn our study of heavy smokers, decreased cg05575921 methylation was strongly associated with smoking but not increased lung cancer risk. The observed association between cg05575921 methylation and increased mortality in adenocarcinoma and small cell histotypes requires further examination. Our results do not support using decreased cg05575921 methylation as a biomarker for lung cancer screening risk stratification.

Dataset Information

Folate/homocysteine metabolism and lung cancer risk among smokers.

Publications

Folate/homocysteine metabolism and lung cancer risk among smokers.

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