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Background
B vitamins and factors related to one-carbon metabolism help to maintain DNA integrity and regulate gene expression, and may affect cancer risk.
Objective
To investigate if one‐carbon metabolism factors are associated with onset of lung cancer.
Design, setting and participants
The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 519,978 participants from ten countries between 1992 and 2000, of whom 385,747 donated blood. By 2006, 899 lung cancer cases were identified and 1,770 controls were individually matched by country, sex, date of birth and date of blood collection. Serum levels were measured for six one-carbon metabolism factors as well as cotinine.
Main outcome measure
Odds ratios of lung cancer by serum levels of four B vitamins (B2, B6, folate and B12), methionine and homocysteine.
Results
Within the entire EPIC cohort the age standardised incidence rates of lung cancer (standardised to the world population, aged 35‐79) were 6.6, 44.9 and 156.1/100,000 person years (pyrs) among never, former, and current smokers for men, respectively. The corresponding incidence rates for women were 7.1, 23.9, and 100.9/100,000 pyrs, respectively.
After accounting for smoking, a lower risk for lung cancer was seen for elevated serum levels of B6 (odds ratio of 4th vs 1st quartile [OR4v1] = 0.44; 95% confidence interval [95% CI], 0.33‐0.60; p for trend [ptrend]< 0.000001), as well as for serum methionine (OR4v1=0.52; 95% CI, 0.39‐0.69; ptrend<0.000001). Similar and consistent decreases in risk were observed in never, former and current smokers, indicating that results were not due to confounding by smoking.
The magnitude of risk was also constant with increasing length of follow‐up, indicating that the associations were not explained by pre‐clinical disease. A lower risk was also seen for serum folate, (OR4v1=0.68; 95% CI, 0.51‐0.90; ptrend=0.001), although this was apparent only for former and current smokers.
When participants were classified by median levels of serum methionine and B6, having above median levels of both resulted in a substantially lower lung cancer risk overall (OR=0.41; 95% CI, 0.31‐0.54), as well as separately among never (OR=0.36; 95% CI, 0.18‐0.71), former (OR=0.51; 95% CI, 0.34‐0.76), and current smokers (OR=0.42; 95% CI, 0.27‐0.65).
Conclusions
Serum levels of vitamin B6 and methionine were inversely associated with risk of lung cancer.