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Variants of the VDR gene and Risk of Colon Cancer (United States)

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Abstract

Objectives: Genetic factors involved in regulating cell growth, such as the vitamin D receptor (VDR) gene, may contribute to the etiology of colon cancer. Methods: Using data from a population-based case–control study of colon cancer and from a family-based study of cases with colon cancer and population-based controls, we evaluated the association between four variants of the VDR gene and risk of colon cancer. Results: The polyA (short), BsmI (BB), and TaqI (tt) variants of the VDR gene were in linkage disequilibrium in this mostly Caucasian population. These variants were associated with reduced risk of colon cancer (OR 0.5, 95% CI 0.3–0.9). The FokI variant was not associated with colon cancer risk. Although estimates of association were imprecise, there were suggestions that associations were slightly stronger for women than men, for people diagnosed at a younger age, and for those with proximal tumors. Consistent associations were observed from sporadic cases of colon cancer from a population-based study as well as from colon cancer cases from a family-based study. There were no interactions observed by family history. Conclusions: These data suggest that molecular variants of the VDR gene may be related to the development of colon cancer. To further define the impact of the VDR gene on cancer etiology, studies to evaluate the association of these variants with diet and lifestyle factors are needed.

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References

  1. Adenis A, Peyrat JP, Hecquet B, et al. (1995) Type I insulin-like growth factor receptors in human colorectal cancer. Eur J Cancer 31A: 50–55.

    Google Scholar 

  2. Baciuchka M, Remacle-Bonnet M, Garrouste F, Favre R, Sastre B, Pommier G (1998) Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) proteolysis in patients with colorectal cancer: possible association with the metastatic potential of the tumor. Int J Cancer 79: 460–467.

    Google Scholar 

  3. Blakesley VA, Stannard BS, Kalebic T, Helman IJ, LeRoith D (1997) Role of the IGF-I receptor in mutagenesis and tumor promotion. J Endocrinol 152: 339–344.

    Google Scholar 

  4. Shabahang M, Buras RR, Davoodi F, Schumaker LM, Nauta RJ, Evans SRT (1993) 1,25-dihydroxyvitamin D3 receptor as a marker of human colon carcinoma cell line differentiation and growth inhibition. Cancer Res 53: 3712–3718.

    Google Scholar 

  5. Feldman D, Malloy PJ, Gross C (1996) Vitamin D: metabolism and action. In: Marcus R, Feldman D, Kelsey J, eds. Osteoporosis. New York: Academic Press, pp. 205–235.

    Google Scholar 

  6. Rozen F, Yang XF, Huynh H, Pollak M (1997) Antiproliferative action of vitamin D-related compounds and insulin-like growth factor-binding protein 5 accumulation. J Natl Cancer Inst 89: 652–656.

    Google Scholar 

  7. Schmidt J, Wittenhagen P, Horder M (1998) [Molecular effects of vitamin D on cell cycle and oncogenesis]. Ugeskr Laeger 160: 4411–4414.

    Google Scholar 

  8. Cross HS, Hulla W, Tong W, Peterlik M (1995) Growth regulation of human colon adenocarcinoma-derived dells by calcium, vitamin D and epidermal growth factor. J Nutr 125: 2004S–2008S.

    Google Scholar 

  9. Tong WM, Kallay E, Hofer H, et al. (1998) Growth regulation of human colon cancer cells by epidermal growth factor and 1,25-dihydroxyvitamin D3 is mediated by mutual modulation of receptor expression. Eur J Cancer 13: 2119–2125.

    Google Scholar 

  10. Ingles SA, Ross RK, Yu MC, et al. (1997) Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptor. J Natl Cancer Inst 89: 166–170.

    Google Scholar 

  11. Feskanich D, Hunter DJ, Willett WC, et al. (1998) Vitamin D receptor genotype and the risk of bone fractures in women. Epidemiology 9: 535–539.

    Google Scholar 

  12. Ruggiero M, Pacini S, Aterini S, Fallai C, Ruggiero C, Pacini P (1998) Vitamin D receptor gene polymorphism is associated with metastatic breast cancer. Oncol Res 10: 43–46.

    Google Scholar 

  13. Gross C, Eccleshall TR, Malloy PJ, Villa ML, Marcus R, Feldman D (1996) The presence of a polymorphism at the translation initiation site of the vitamin D receptor gene is associated with low bone mineral density in postmenopausal Mexican-American women. J Bone Min Res 11: 1850–1855.

    Google Scholar 

  14. Slattery ML, Potter JD, Caan BJ, et al. (1997) Energy balance and colon cancer: beyond physical activity. Cancer Res 57: 75–80.

    Google Scholar 

  15. Lewis CM, Neuhausen SL, Daley D, et al. (1996) Genetic heterogeneity and upmapped genes for colorectal cancer. Cancer Res 56: 1382–1388.

    Google Scholar 

  16. McClure L, Ecclehall TR, Gross C, et al. (1997) Vitamin D receptor polymorphisms bone mineral density, and bone metabolism in postmenopausal Mexican-American women. J Bone Min Res 12: 234–239.

    Google Scholar 

  17. Lundin AC, Soderkvist P, Eriksson B, Bergman-Jungestrom M, Wingren S (1999) Association of breast cancer progression with a vitamin D receptor gene polymorphism. South-East Sweden Breast Cancer Group. Cancer Res 59: 2332–2334.

    Google Scholar 

  18. Harris SS, Eccleshall TR, Gross C, Dawson-Hughes B, Feldman D (1997) The vitamin D receptor start condon polymorphism (FokI) and bone metabolism in postmenopausal American black and white women. J Bone Min Res 12: 1043–1048.

    Google Scholar 

  19. Ingles SA, Coetzee GA, Ross RK, et al. (1998) Association of prostate cancer with vitamin D receptor haplotypes in African Americans. Cancer Res 58: 1620–1623.

    Google Scholar 

  20. Evans SRT, Nolla J, Hanfelt J, Shabahang M, Nauta RJ, Shchepotin IB (1998) Vitamin D receptor expression as a predictive marker of biological behavior in human colorectal cancer. Clin Cancer Res 4: 1591–1595.

    Google Scholar 

  21. Durrin LK, Haile RW, Ingles SA, Coetzee GA (1999) Vitamin D receptor 3′-untranslated region polymorphisms: lack of effect on mRNA stability. Biochim Biophys Acta 1453: 311–320.

    Google Scholar 

  22. Ingles SA, Haile RW, Henderson BE, et al. (1997) Strength of linkage disequilibrium between two vitamin D receptor markers in five ethnic groups: implications for association studies. Cancer Epidemiol Biomarkers Prev 6: 93–98.

    Google Scholar 

  23. Martinez ME, Willett WC (1998) Calcium, vitamin D, and colorectal cancer: a review of the epidemiologic evidence. Cancer Epidemiol Biomarkers Prev 7: 163–168.

    Google Scholar 

  24. Lee IM, Paffenbarger RS (1994) Physical activity and its relation to cancer risk: a prospective study of college alumni. Med Sci Sports Exerc 7: 831–837.

    Google Scholar 

  25. Slattery ML, Edwards SL, Ma KN, Friedman FG, Potter JD (1997) Physical activity and colon cancer: a public health perspective. Annals Epidemiol 7: 137–145.

    Google Scholar 

  26. Potter JD, Slattery ML, Bostick RM, Gapstur SM (1993) Colon cancer: a review of the epidemiology. Epidemiol Rev 15: 499–545.

    Google Scholar 

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Authors and Affiliations

  1. Health Research Center, Department of Family and Preventive Medicine, University of Utah, 391 Chipeta Way, Suite G, Salt Lake City, Utah, 84108, USA

    Martha L. Slattery

  2. Department of Medical Informatics, University of Utah, Salt Lake City, Utah, USA

    Kazuko Yakumo, Michael Hoffman & Susan Neuhausen

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  1. Martha L. Slattery
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  2. Kazuko Yakumo
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  3. Michael Hoffman
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  4. Susan Neuhausen
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Slattery, M.L., Yakumo, K., Hoffman, M. et al. Variants of the VDR gene and Risk of Colon Cancer (United States). Cancer Causes Control 12, 359–364 (2001). https://doi.org/10.1023/A:1011280518278

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