Identification of D19S246 as a novel lung adenocarcinoma susceptibility locus by genome survey with 10-cM resolution microsatellite markers.
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.
Yanagitani
Noriko
N
Biology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Kohno
Takashi
T
Kim
Jeong-Gyoon
JG
Kunitoh
Hideo
H
Tamura
Tomohide
T
Takei
Yoshikazu
Y
Tsuchiya
Satoshi
S
Saito
Ryusei
R
Yokota
Jun
J
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000235:genetics; D003625:Data Collection; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology / Q000235:genetics; D013223:Statistics as Topic
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm