Association of a polymorphism of the phospholipase D2 gene with the prevalence of colorectal cancer.
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.
Yamada
Yoshiji
Y
Department of Gene Therapy, Gifu International Institute of Biotechnology, 2193-128 Mitake, 505-0116, Gifu, Japan.
Hamajima
Nobuyuki
N
Kato
Tomoyuki
T
Iwata
Hiroji
H
Yamamura
Yoshitaka
Y
Shinoda
Masayuki
M
Suyama
Motokazu
M
Mitsudomi
Tetsuya
T
Tajima
Kazuo
K
Kusakabe
Suzuno
S
Yoshida
Hitoshi
H
Banno
Yoshiko
Y
Akao
Yukihiro
Y
Tanaka
Masashi
M
Nozawa
Yoshinori
Y
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
C105606:phospholipase D2; D010739:Phospholipase D