Population based mapping of pulmonary adenoma susceptibility 1 locus

Pulmonary adenoma susceptibility 1 (Pas1), the major locus affecting inheri ted predisposition to lung tumor development in mice, maps near the Kras2 g ene. We previously reported a significant association between a KRAS2/RsaI polymorphism and the risk and prognosis of lung adenocarcinoma (ADCA) in th e Italian population. In the present case-control study, we examined 269 lu ng ADCA patients, 121 squamous cell lung carcinoma patients, and 632 health y individuals (general population controls) in the Japanese population with genetic markers spanning similar to 1200 kb in the KRAS2 region. Allele-sp ecific oligonucleotide hybridization revealed the same KRAS2/RsaI polymorph ism associated with risk and prognosis as in Italian lung ADCA patients; th e polymorphism was significantly associated with clinical stage (P < 0.001) and survival rate (log rank = 0.0014), confirming the mapping of PAS1 and pointing to the role of this locus in human lung cancer.