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

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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 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.

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Abbreviations

PLD :

Phospholipase D

PC :

Phosphatidylcholine

PA :

Phosphatidic acid

PIP 2 :

Phosphatidylinositol 4,5-bisphosphate

SNP :

Single nucleotide polymorphism

PCR-CTPP :

Polymerase chain reaction with confronting two-pair primers

PE :

Phosphatidylethanolamine

DPPC :

Dipalmitoylphosphatidylcholine

PBut :

Phosphatidylbutanol

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Acknowledgements

We thank Michiyo Tani for genotyping. This work was supported in part by Grants-in-Aid for Scientific Research on Priority Areas 09273104 and 10212204 and Grants-in-Aid for Scientific Research (B) 12470042 and (C) 12680633 from the Ministry of Education, Science, Sports, and Culture of Japan.

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Authors and Affiliations

  1. Department of Gene Therapy, Gifu International Institute of Biotechnology, 2193-128 Mitake, 505-0116, Gifu, Japan

    Yoshiji Yamada & Masashi Tanaka

  2. Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan

    Nobuyuki Hamajima & Kazuo Tajima

  3. Department of Digestive Surgery, Aichi Cancer Center, Nagoya, Japan

    Tomoyuki Kato & Yoshitaka Yamamura

  4. Department of Breast Surgery, Aichi Cancer Center, Nagoya, Japan

    Hiroji Iwata

  5. Department of Rehabilitation Service, Aichi Cancer Center, Nagoya, Japan

    Masayuki Shinoda

  6. Department of Outpatient Clinic, Aichi Cancer Center, Nagoya, Japan

    Motokazu Suyama

  7. Department of Thoracic Surgery, Aichi Cancer Center, Nagoya, Japan

    Tetsuya Mitsudomi

  8. Department of Environmental Cell Response, Gifu International Institute of Biotechnology, 2193-128 Mitake, 505-0116, Gifu, Japan

    Suzuno Kusakabe & Yoshinori Nozawa

  9. Department of Genetic Diagnosis, Gifu International Institute of Biotechnology, 2193-128 Mitake, 505-0116, Gifu, Japan

    Hitoshi Yoshida & Yukihiro Akao

  10. Department of Biochemistry, Gifu University School of Medicine, Gifu, Japan

    Yoshiko Banno

Authors
  1. Yoshiji Yamada
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  2. Nobuyuki Hamajima
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  3. Tomoyuki Kato
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  4. Hiroji Iwata
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  5. Yoshitaka Yamamura
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  6. Masayuki Shinoda
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  7. Motokazu Suyama
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  8. Tetsuya Mitsudomi
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  9. Kazuo Tajima
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  10. Suzuno Kusakabe
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  11. Hitoshi Yoshida
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  12. Yoshiko Banno
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  13. Yukihiro Akao
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  14. Masashi Tanaka
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  15. Yoshinori Nozawa
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Corresponding author

Correspondence to Yoshinori Nozawa.

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Yamada, Y., Hamajima, N., Kato, T. et al. Association of a polymorphism of the phospholipase D2 gene with the prevalence of colorectal cancer. J Mol Med 81, 126–131 (2003). https://doi.org/10.1007/s00109-002-0411-x

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  • DOI: https://doi.org/10.1007/s00109-002-0411-x

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