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Identification of D19S246 as a Novel Lung Adenocarcinoma Susceptibility Locus by Genome Survey with 10-cM Resolution Microsatellite Markers¹

Biology Division, National Cancer Center Research Institute, Tokyo 104-0045 [N. Y., T. K., J-G. K., J. Y.]; First Department of Internal Medicine, Gunma University School of Medicine, Gunma 371-8511 [N. Y., Y. T., S. T., R. S.]; and Division of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045 [H. K., T. T.], Japan

Adenocarcinoma is now the most common histological subtype of lung cancer;however, genetic factors that affect cancer susceptibility are largely unknown. In this study, we performed a systematic survey of the human genome with an average resolution of 10 cM to identify loci that could help us target novel risk genes for lung adenocarcinoma using linkage disequilibrium. Genotyping of DNA "pools" from 100 lung adenocarcinoma cases and 100 controls, respectively, for 322 microsatellite loci dispersed in the human genome led us to identify 5 loci at which allele distribution was significantly (P < 0.05) or marginally (0.05 P < 0.1) different between the cases and controls. One of the 5 loci, D19S246 at chromosome 19q13.3, showed significant differences both in the allele and genotype distributions in the subsequent analysis in which 239 lung adenocarcinoma cases and 63 controls were added to the 100 cases and 100 controls used for the initial screening (P = 0.037 and P = 0.026, respectively), whereas the remaining 4 loci did not. These results suggest that the chromosome 19q13.3 region encompassing D19S246 contains a gene(s) of which the genetic polymorphisms are associated with lung adenocarcinoma risk and are in linkage disequilibrium with the D19S246 locus.

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