Population-based mapping of pulmonary adenoma susceptibility 1 locus.
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 approximately 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.
Dragani
T A
TA
National Cancer Center Research Institute, Tokyo, Japan. dragani@istitutotumori.mi.it
Hirohashi
S
S
Juji
T
T
Kawajiri
K
K
Kihara
M
M
Ono-Kihara
M
M
Manenti
G
G
Nomoto
T
T
Sugimura
H
H
Genka
K
K
Yokota
J
J
Takahashi
T
T
Mitsudomi
T
T
Nagao
M
M
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D000368:Aged; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D016019:Survival Analysis; D018631:ras Proteins
D005819:Genetic Markers; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D015252:Deoxyribonucleases, Type II Site-Specific; C040158:GTAC-specific type II deoxyribonucleases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins