Specific aims
1. To accurately measure the association between circulating levels of vitamin B6, methionine and folate, as well as other B-vitamins and related compounds (including homocysteine, vitamin B2 and vitamin B12) and subsequent lung cancer risk
2. To provide accurate risk estimates for groups stratified by B-vitamin levels and smoking status (in particular in never and ex-smokers)
3. To analyze the effect of having low levels of multiple B-vitamins and related compounds, and test the hypothesis that their effects are, at least partially, independent
4. To calculate the within-person variation of B-vitamins and adjust results for regression dilution that occurs because of this variation
5. To analyze SNPs known to be associated with B-vitamin levels based on recent genome-wide studies, including additional case-control studies from the ILCCO consortium, in order to obtain independent and robust evidence of a causal effect of these B-vitamins
Participating cohorts
1. To provide 500 µL plasma or serum for prospectively collected lung cancer cases and controls (individually matched 1:1)
2. To provide repeated plasma or serum samples for a subset of included controls
3. To provide detailed questionnaire data on risk factors including smoking variables, demographic, and dietary variables
4. To provide DNA (500 ng) in order to analyze specific single nucleotide polymorphisms known to influence factors of one-carbon metabolism
5. To provide follow-up data on vital status and cause of death

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