title: Association of a polymorphism of the phospholipase D2 gene with the prevalence of colorectal cancer.
abstract: Phospholipase D plays an important role in transmembrane signaling in a variety of cell types and its activity is increased in certain cancers, suggesting that it also contributes to tumorigenesis. A C-->T transition at nucleotide 1814 of the human phospholipase D(2) gene, which results in a Thr-->Ile substitution at amino acid 577, was noted in the GenBank database. The relationship of this polymorphism to the prevalence of cancer of the esophagus, stomach, colon-rectum, lung, and breast in Japanese was investigated in a case-control study. The genotype of the phospholipase D(2) gene was determined by the polymerase chain reaction with confronting two-pair primers. Multivariate logistic regression analysis with adjustment for age, gender, and smoking status revealed that the frequency of the T allele of the 1814C-->T polymorphism was significantly higher in individuals with colorectal cancer than in controls. A significant association of the polymorphism with the prevalence of colorectal cancer was found in analyses assuming either dominant (TT+CT vs. CC) or additive (CT vs. CC) effects of the T allele, but the T allele was not associated with the prevalence of esophageal, gastric, lung, or breast cancer. The activities of phospholipase D in cell lysates or membrane fractions did not differ between cells transfected with cDNAs encoding the Thr-577 or Ile-577 variants of phospholipase D(2). These results suggest that the phospholipase D(2) gene is a susceptibility locus for colorectal cancer in Japanese individuals, although a functional effect of the 1814C-->T (Thr577Ile) polymorphism was not detected.
authors.affiliation: Department of Gene Therapy, Gifu International Institute of Biotechnology, 2193-128 Mitake, 505-0116, Gifu, Japan.
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kato
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yamamura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shinoda
authors.forename: Motokazu
authors.initials: M
authors.lastname: Suyama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima
authors.forename: Suzuno
authors.initials: S
authors.lastname: Kusakabe
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Banno
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akao
authors.forename: Masashi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nozawa
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010739:Phospholipase D / Q000235:genetics*; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D012907:Smoking
chemical_list: C105606:phospholipase D2; D010739:Phospholipase D