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  • The C/C−13910 genotype of adult-type hypolactasia is associated with an increased risk of colorectal cancer in the Finnish population

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Colorectal cancer
The C/C−13910 genotype of adult-type hypolactasia is associated with an increased risk of colorectal cancer in the Finnish population
  1. H Rasinperä1,
  2. C Forsblom2,
  3. N S Enattah3,
  4. P Halonen4,
  5. K Salo5,
  6. M Victorzon6,
  7. J-P Mecklin7,
  8. H Järvinen8,
  9. S Enholm1,
  10. G Sellick9,
  11. H Alazzouzi10,
  12. R Houlston9,
  13. J Robinson11,
  14. P-H Groop2,
  15. I Tomlinson12,
  16. S Schwartz Jr10,
  17. L A Aaltonen1,
  18. I Järvelä13,
  19. The FinnDiane Study Group
  1. 1Department of Medical Genetics, University of Helsinki, Finland
  2. 2Department of Medicine, Division of Nephrology, Helsinki University Hospital, and Folkhälsan Institute of Genetics, Folkhälsan Research Centre, Helsinki, Finland
  3. 3Department of Medical Genetics, University of Helsinki, Finland, and Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
  4. 4Information Technology Centre, University of Kuopio, Kuopio, Finland
  5. 5Department of Pathology, Vaasa Central Hospital, Vaasa, Finland
  6. 6Department of Gastrointestinal Surgery, Vaasa Central Hospital, Vaasa, Finland
  7. 7Department of Surgery, Jyväskylä Central Hospital, Jyväskylä, Finland
  8. 8Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
  9. 9Institute of Cancer Research, Sutton, Surrey, UK
  10. 10Centre d’Investigacions en Bioquímica i Biologia Molecular (CIBBIM), Hospital Universitari Vall d’Hebron, Barcelona, Spain
  11. 11Colorectal Cancer Unit, Cancer Research UK, St Mark’s Hospital, Watford Rd, Harrow, UK
  12. 12Colorectal Cancer Unit, Cancer Research UK, St Mark’s Hospital, Watford Road, Harrow, UK, and Molecular and Population Genetics Laboratory, Cancer Research UK, Lincoln’s Inn Fields, London, UK
  13. 13Helsinki University Central Hospital, Laboratory of Molecular Genetics, Helsinki, Finland, and Department of Medical Genetics, University of Helsinki, Finland
  1. Correspondence to:
    Dr I Järvelä
    Helsinki University Central Hospital, Laboratory of Molecular Genetics, Haartmaninkatu 2, PO Box 140, FIN-00290 Helsinki, Finland; irma.jarvelahus.fi

Abstract

Background and aims: The role of nutrition in the pathogenesis of colorectal cancer is not fully understood. Milk products are an essential part of human nutrition in Western countries. Absorption of lactose, the main sugar of milk, is regulated by the activity of the lactase enzyme in the gut wall. The activity of lactase is genetically determined and is associated with a C/T single nucleotide polymorphism residing 13910 bp upstream of the lactase coding sequence. Here we have studied the relationship between the C/T−13910 polymorphism and colorectal cancer in Finnish, British, and Spanish populations.

Patients and methods: A total of 2766 subjects, including 963 Finnish, 283 British, and 163 Spanish subjects with colorectal cancer, and 773 Finnish, 363 British, and 221 Spanish control subjects, were genotyped for the C/T−13910 variant by polymerase chain reaction minisequencing.

Results: The C/C−13910 genotype, which is a robust molecular marker of low lactase activity (lactase non-persistence), was found to significantly associate with the risk of colorectal cancer (p = 0.015) in the Finnish subjects, with an odds ratio of 1.40 (95% confidence interval 1.07–1.85). No association was found with site, histology, or stage of the tumour. No significant risk was detected in the British or Spanish populations.

Conclusion: Low lactase enzyme activity, defined by genotyping of the C/T−13910 variant, may increase the risk of colorectal cancer. Further studies are warranted to investigate the role of milk and other dairy products in the pathogenesis of colon cancer in different populations.

  • LPH, lactase-phlorizin hydrolase
  • PCR, polymerase chain reaction
  • OR, odds ratio
  • LM, lactose malabsorption
  • adult-type hypolactasia
  • colorectal cancer
  • single nucleotide polymorphism
  • lactase
  • risk

https://doi.org/10.1136/gut.2004.055939

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    Footnotes

    • Conflict of interest: None declared.