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.