Abstract
BackgroundFolate and homocysteine are involved in DNA synthesis and methylation processes, which are deregulated during carcinogenesis.ObjectivesThe 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 designThe 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.ResultsSerum 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).ConclusionThese results suggest that, in the population consisting of heavy smokers, high folate levels add to the cancerogenic effect of smoking.
Highlights
Lung cancer accounts for the highest number of cancer deaths globally [1], with cigarette smoking remaining the most prominent risk factor [2].Folate plays a pivotal role in cell metabolism by providing metabolites necessary for DNA synthesis and repair, as well as for methylation of DNA, proteins and lipids
Serum folate concentrations above the median (> 17.5 nmol/l among the healthy controls) were associated with an increased lung cancer risk
An analogous trend was observed when the population was analysed after subdivision according to red blood cell (RBC) folate concentrations, that is, above a value of 506.5 nmol/l (OR, 1.53; 95% confidence intervals (CI), 0.95–2.47; P = 0.084)
Summary
Folate (vitamin B9) plays a pivotal role in cell metabolism by providing metabolites necessary for DNA synthesis and repair, as well as for methylation of DNA, proteins and lipids. While reduced folates are crucial C1 (one-carbon, methyl group) cycle intermediates, several enzymes involved in their metabolism require other cofactors from the B-vitamin group, such as B12 (Fig 1). High homocysteine concentration is a marker of increased stroke risk, and this has been suggested to result from long-term inadequate B-vitamins levels and endothelial dysfunction. There is accumulating evidence that folic acid interventions aimed at lowering homocysteine levels decrease the incidence of stroke [5]. Folate and homocysteine are involved in DNA synthesis and methylation processes, which are deregulated during carcinogenesis
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