Association of RFC 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: The present 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% confidence interval (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 for 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 levels (<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 for 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.