Identification of the causal variants for these loci will be challenging, contingent on resequencing and fine mapping studies. While in part speculative current data provides information on the probable genetic basis of the associations at 15q25.1, 5p15.33, and 6p21.33. While there is strong evidence that a major component (some would assert all) of the lung cancer risk associated with 15q25.1 is mediated through propensity to smoke and hence a higher exposure to smoking-related carcinogens(3, 11), it does not exclude the possibility 15q25.1 variation also has a direct effect on lung cancer risk as has also been proposed(2, 11).
