Circulating pyridoxal-5'-phosphate (PLP) has been linked to
lung cancer risk. The PAr index, defined as the ratio
4-pyridoxic acid/(
pyridoxal + PLP), reflects increased
vitamin B6 catabolism during
inflammation. PAr has been defined as a marker of
lung cancer risk in a prospective cohort study, but analysis of a larger numbers of cases are needed to deepen the significance of this study. Here, we conducted a nested case-control study within the European Prospective Investigation into
Cancer and Nutrition (EPIC, n = 521,330), which included 892 incident
lung cancer cases and 1,748 controls matched by center, gender, date of blood collection, and date of birth. The association of PAr with risk of
lung cancer was evaluated by using conditional logistic regression. Study participants with elevated PAr experienced higher risk of
lung cancer in a dose-response fashion, with a doubling in PAr levels associated with 52% higher odds of
lung cancer after adjustment for tobacco smoking, serum
cotinine levels, educational attainment, and BMI [OR, 1.52; 95% confidence interval (CI) 1.27-1.81; P < 0.001]. Additional adjustment for intake of vegetables and fruits and physical activity did not materially affect risk association. The association of PAr with
lung cancer risk was similar in both genders but slightly stronger in former smokers and in participants diagnosed with
squamous cell carcinoma. This study provides robust evidence that increased
vitamin B6 catabolism is independently associated with a higher risk of future
lung cancer.Significance: This large cohort study firmly establishes an association between an index of
vitamin B6 levels with
lung cancer risk.
Cancer Res; 78(1); 302-8. ©2017 AACR.