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[Cancer Research 60, 5017-5020, September 15, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Population-based Mapping of Pulmonary Adenoma Susceptibility 1 Locus1

Tommaso A. Dragani2, Setsuo Hirohashi, Takeo Juji, Kaname Kawajiri, Masahiro Kihara3, Masako Ono-Kihara3, Giacomo Manenti, Tomoko Nomoto, Haruhiko Sugimura, Keiichiro Genka, Jun Yokota, Takashi Takahashi, Tetsuya Mitsudomi and Minako Nagao

National Cancer Center Research Institute, Tokyo, Japan [T. A. D., S. H., T. N., J. Y., M. N.]; Istituto Nazionale Tumori, 20133 Milan, Italy [T. A. D., G. M.]; Japanese Red Cross Central Blood Center, Tokyo, Japan [T. J.]; Saitama Cancer Center Research Institute, Saitama, Japan [K. K.]; Kanagawa Cancer Center Research Institute, Yokohama, Japan [M. K., M. O-K.]; Hamamatsu University of Medicine, Hamamatsu, Japan [H. S.]; National Okinawa Hospital, Okinawa, Japan [K. G.]; and Aichi Cancer Center Research Institute, Nagoya, Japan [T. T., T. M.]

Pulmonary adenoma susceptibility 1 (Pas1), the major locus affecting inherited predisposition to lung tumor development in mice, maps near the Kras2 gene. We previously reported a significant association between a KRAS2/RsaI polymorphism and the risk and prognosis of lung adenocarcinoma (ADCA) in the Italian population. In the present case-control study, we examined 269 lung ADCA patients, 121 squamous cell lung carcinoma patients, and 632 healthy individuals (general population controls) in the Japanese population with genetic markers spanning ~1200 kb in the KRAS2 region. Allele-specific oligonucleotide hybridization revealed the same KRAS2/RsaI polymorphism associated with risk and prognosis as in Italian lung ADCA patients; the 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.




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