We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk.
In this study, immunohistochemistry and in situ hybridization (ISH) for CYP2A6 with human lung cancer tissues (n=31) obtained by surgical resection showed significantly higher immunoreactivity in the cases with lymph node metastasis.
Other mutant alleles reducing the CYP2A6 activity, besides CYP2A6*4C, also reduced the risk of lung cancer in smokers, particularly of squamous-cell carcinoma and small-cell carcinoma, both smoking-related cancers.
This effect was mainly limited to squamous-cell carcinoma and to non-smokers, although a joint effect of CYP2A6 deletion and tobacco smoking on lung cancer risk was observed among heavy smokers.