Association of Reduced Folate Carrier G80A Polymorphism With Lung Cancer Susceptibility in a Hypertensive Population: A Nested Case–Control Study

Background

Polymorphisms of the folate-associated one-carbon metabolism (OCM) pathway genes may regulate certain susceptibilities to cancer. G80A, a polymorphism in the reduced folate carrier (RFC) gene, may be associated with cancer risk, although the results obtained from previous studies have been inconsistent.

Objectives

This study aimed to evaluate the association of G80A with lung cancer among a Chinese population and to examine the potential effect modifiers.

Methods

A nested, case–control study was performed in a population from the China H-type Hypertension Registry Study (CHHRS), in which 492 cases of lung cancer incidence and 1:1 matched controls were enrolled. RFC G80A variants were genotyped, and a series of metabolites in the OCM metabolic pathway were detected. Conditional logistic regression was used to model the association between this variant and lung cancer.

Results

After adjusting for potential confounders, compared with GG carriers, AG carriers showed a trend of increased lung cancer risk [adjusted odds ratio (OR): 1.37; 95% CI: 0.97, 1.94], and AA carriers showed a significantly increased risk (adjusted OR: 1.86; 95% CI: 1.16, 2.97; P = 0.010; P-trend = 0.009). In subsequent stratification analyses, a significant interaction effect from the pronounced risk-enhancing effect of the 80AA/GG genotypes was observed in participants with lower baseline serum methionine concentrations (<4.6 μg/mL—adjusted OR: 2.63; 95% CI: 1.40, 4.96; compared with ≥4.6 μg/mL—adjusted OR: 1.17; 95% CI: 0.82, 1.66; P-interaction = 0.030).

Conclusions

Taken together, these findings suggest that RFC G80A may influence the susceptibility of lung cancer and may also be a potential biomarker for lung cancer prevention.