Association of a polymorphism of the phospholipase D2 gene with the prevalence of colorectal cancer.

Autor: Yoshiji Yamada, Nobuyuki Hamajima, Tomoyuki Kato, Hiroji Iwata, Yoshitaka Yamamura, Masayuki Shinoda, Motokazu Suyama, Tetsuya Mitsudomi, Kazuo Tajima, Suzuno Kusakabe, Hitoshi Yoshida, Yoshiko Banno, Yukihiro Akao, Masashi Tanaka, Yoshinori Nozawa
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Zdroj: Journal of Molecular Medicine; Feb2003, Vol. 81 Issue 2, p126-131, 6p
Abstrakt: 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 D2 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 D2 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 D2. These results suggest that the phospholipase D2 gene is a susceptibility locus for colorectal cancer in Japanese individuals, although a functional effect of the 1814C→T (Thr577Ile) polymorphism was not detected. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index