Nucleotide variations in genes encoding plasminogen activator inhibitor-2 and serine proteinase inhibitor B10 associated with prostate cancer.
Genes encoding the serine proteinase inhibitor B family (SERPINBs) are mainly clustered on human chromosome 18 (18q21). Several serpins are known to affect malignant phenotypes of tumor cells, so aberrant genetic variants in this molecular family are candidates for conferring susceptibility for risk of cancer. We investigated whether eight selected non-synonymous variations within SERPINB loci at 18q21 might be associated with risk of prostate cancer in Japanese men. A case-control study involving 292 prostate-cancer patients and 384 controls revealed significant differences in regard to distribution of four missense variations in genes encoding plasminogen activator inhibitor 2 (PAI2) and SERPINB10. The most significant association was detected for the N120D polymorphism in the PAI2 gene (P = 5.0 x 10(-5)); men carrying the 120-N allele (120-N/N and 120-N/D genotypes) carried a 2.4-fold increased risk of prostate cancer (95% confidence interval 1.45-4.07). Associations were also detected for three other missense polymorphisms in those two genes. Strong linkage disequilibrium in the region encompassing PAI2 and SERPINB10 extended to about 50 kbp. The results suggested that missense variations in one or both of these genes confer important risks for prostate cancer, and may be themselves tumorigenic. Although confirmative replication studies on larger cohorts are awaited, clinical examination of these variations may become useful for identifying individuals at high risk for prostate cancer.
Shioji
Go
G
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.|Department of Urology, Nippon Medical School, Tokyo, Japan.
Ezura
Yoichi
Y
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan. ezura.mph@mri.tmd.ac.jp.|Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan. ezura.mph@mri.tmd.ac.jp.
Nakajima
Toshiaki
T
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.
Ohgaki
Kenji
K
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.|Department of Urology, Nippon Medical School, Tokyo, Japan.
Fujiwara
Hiromichi
H
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.|Department of Urology, Nippon Medical School, Tokyo, Japan.
Kubota
Yoshinobu
Y
Department of Urology, Yokohama City University Medical School, Yokohama, Japan.
Ichikawa
Tomohiko
T
Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Inoue
Katsuki
K
Department of Urology, Showa University Fujigaoka Hospital, Yokohama, Japan.
Shuin
Taro
T
Department of Urology, Kochi Medical University, Kochi, Japan.
Habuchi
Tomonori
T
Department of Urology, Akita University, Akita, Japan.
Ogawa
Osamu
O
Department of Urology, University of Kyoto Medical School, Kyoto, Japan.
Nishimura
Taiji
T
Department of Urology, Nippon Medical School, Tokyo, Japan.
Emi
Mitsuru
M
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.
D000483:Alleles; D016022:Case-Control Studies; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020125:Mutation, Missense; D017396:Plasminogen Activator Inhibitor 2 / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D040641:Quantitative Trait Loci / Q000235:genetics*; D012307:Risk Factors; D015843:Serpins / Q000235:genetics* / Q000378:metabolism
D017396:Plasminogen Activator Inhibitor 2; C096854:SERPINB10 protein, human; D015843:Serpins