The second additional locus identified was at 4q21, with the nonsynonmous variant rs1494961 located in the HEL308 gene (preplication = 2×10−5, pcombined = 1×10−8) (Table 1). In combined analysis, the association tended to be more pronounced in younger ages and smokers (Figure 4). Given the possible role of the HEL308 in DNA repair, we also investigated the possibility that rs1494961 may play a role in lung cancer susceptibility by genotyping rs1494961 in a series of 5,652 lung cancer cases and 9,338 controls. We noted a similar association between rs1494961 and lung cancer (OR = 1.09, p = 3×10−4) from nine lung cancer studies, even when we excluded 1,844 cases and 2,735 controls where controls overlapped with the central European UADT study (OR = 1.09, p = 0.005).
