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Vitamin D receptor polymorphisms and risk of colorectal adenomas (United States)

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Abstract

Objective: The purpose of this study was to determine whether vitamin D receptor (VDR) gene polymorphisms influence risk of colorectal adenoma.

Methods: Polymorphisms in the 5′ and 3′ ends of the VDR gene were genotyped for 373 colorectal adenoma cases and 394 controls.

Results: Overall, there was no significant association between the 5′ (FokI) or the 3′ (BsmI) polymorphisms and adenoma risk. However, risk of large (>1 cm) adenomas decreased with increasing copies of the FokI f allele (p = 0.04). Compared to the FF genotype, odds ratios for the Ff and ff genotypes were 0.79 (95% CI 0.44–1.41) and 0.32 (95% CI 0.11–0.91), respectively. FokI genotype was more strongly related to large adenoma risk among subjects with low dietary calcium intake (ORFf = 0.48; 95% CI 0.17–1.3; ORff = 0.21; 95% CI 0.04–1.3), low dietary vitamin D intake (ORFf = 0.25; 95% CI 0.09–0.69; ORff = 0.22; 95% CI 0.04–1.2), or dark skin color (ORFf = 0.66; 95% CI 0.27–1.6; ORff = 0.10; 95% CI 0.01–1.0).

Conclusion: These results suggest that VDR FokI genotype influences development of colorectal adenomas, and that the effect may be modified by calcium and vitamin D status.

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References

  1. Garland CF, Garland FC (1980) Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol 9: 227–231.

    Google Scholar 

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

    Google Scholar 

  3. Garland CF, Comstock GW, Garland FC, Helsing KJ, Shaw EK, Gorham ED (1989) Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet 2: 1176–1178.

    Google Scholar 

  4. Braun MM, Helzlsouer KJ, Hollis BW, Comstock GW (1995) Colon cancer and serum vitamin D metabolite levels 10–17 years prior to diagnosis. Am J Epidemiol 142: 608–611.

    Google Scholar 

  5. Tangrea J, Helzlsouer K, Pietinen P, et al. (1997) Serum levels of vitamin D metabolites and the subsequent risk of colon and rectal cancer in Finnish men. Cancer Causes Control 8: 615–662.

    Google Scholar 

  6. Studzinski GP, McLane JA, Uskokovic MR (1993) Signaling pathways for vitamin D-induced differentiation: implications for therapy of proliferative and neoplastic diseases. [Review] Crit Rev Eukaryot Gene Exp 3: 279–312.

    Google Scholar 

  7. Lointier P, Meggouh F, Dechelotte P, et al. (1991) 1,25-Dihydroxyvitamin D3 receptors and human colon adenocarcinoma. Br J Surg 78: 435–439.

    Google Scholar 

  8. Buras RR, Schumaker LM, Davoodi F, et al. (1994) Vitamin D receptors in breast cancer cells. Breast Cancer Res Treat 31: 191–202.

    Google Scholar 

  9. Pechl DM, Skowronski RJ, Leung GK, Wong ST, Stamey TA, Feldman D (1994) Antiproliferative effects of 1,25-dihydroxyvitamin D3 on primary cultures of human prostatic cells. Cancer Res 54: 805–810.

    Google Scholar 

  10. Shabahang M, Buras RR, Davoodi F, Schumaker LM, Nauta RJ, Evans SR (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 

  11. Cross HS, Pavelka M, Slavik J, Peterlik M (1992) Growth control of human colon cancer cells by vitamin D and calcium in vitro. J Natl Cancer Inst 84: 1355–1357.

    Google Scholar 

  12. Evans SR, Nolla J, Hanfelt J, Shabahang M, Nauta RJ, Schepotin 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 

  13. Cooper GS, Umbach DM (1996) Are vitamin D receptor polymorphisms associated with bone mineral density? A meta-analysis. J Bone Miner Res 11: 1841–1849.

    Google Scholar 

  14. 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 Miner Res 11: 1850–1855.

    Google Scholar 

  15. Arai H, Miyamoto K, Taketani Y, et al. (1997) A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J Bone Miner Res 12: 915–921.

    Google Scholar 

  16. Harris SS, Eccleshall TR, Gross C, Dawson-Hughes B, Feldman D (1997) The vitamin D receptor start codon polymorphism (FokI) and bone mineral density in premenopausal American black and white women. J Bone Miner Res 12: 1043–1048.

    Google Scholar 

  17. Gennari L, Becherini L, Mansani R, et al. (1999) FokI polymorphism at translation initiation site of the vitamin D receptor gene predicts bone mineral density and vertebral fractures in postmenopausal Italian women. J Bone Miner Res 14: 1379–1386.

    Google Scholar 

  18. Taylor JA, Hirvonen A, Watson M, Pittman G, Mohler JL, Bell DA (1996) Association of prostate cancer with vitamin D receptor gene polymorphism. Cancer Res 56: 4108–4110.

    Google Scholar 

  19. 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 

  20. Curran JE, Vaughan T, Lea RA, Weinstein SR, Morrison NA, Griffiths LR (1999) Association of A vitamin D receptor polymorphism with sporadic breast cancer development. Int J Cancer 83: 723–726.

    Google Scholar 

  21. Ingles SA, Garcia DG, Wang W, et al. (2000) Vitamin D receptor genotype and breast cancer in Latinas. Cancer Causes Control 11: 25–30.

    Google Scholar 

  22. Lin H, Probst-Hensch NM, Ingles SA, et al. (1995) Glutathione transferase (GSTM1) null genotype, smoking, and prevalence of colorectal adenomas. Cancer Res 55: 1224–1226.

    Google Scholar 

  23. Haile RW, Witte JS, Longnecker MP (1997) A sigmoidoscopy-based case control study of polyps: macronutrients, fiber and meat consumption. Int J Cancer 73: 497–502.

    Google Scholar 

  24. Morrison NA, Qi JC, Tokita A, et al. (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367: 284–287.

    Google Scholar 

  25. Lucotte G, Mercier G, Burckel A (1999) Fok I polymorphism at the human vitamin D receptor gene locus in Europeans and Africans. Clin Genet 55: 281–282.

    Google Scholar 

  26. Eccleshall TR, Garnero P, Gross C, Delmas PD, Feldman D (1998) Lack of correlation between start codon polymorphism of the vitamin D receptor gene and bone mineral density in premenopausal French women: the OFELY study. J Bone Miner Res 13: 31–35.

    Google Scholar 

  27. Ferrari S, Rizzoli R, Manen D, Slosman D, Bonjour JP (1998) Vitamin D receptor gene start codon polymorphisms (FokI) and bone mineral density: interaction with age, dietary calcium, and 3'-end region polymorphisms. J Bone Miner Res 13: 925–930.

    Google Scholar 

  28. Correa P, Rastad J, Schwarz P, et al. (1999) The vitamin D receptor (VDR) start codon polymorphism in primary hyperparathyroidism and parathyroid VDR messenger ribonucleic acid levels. J Clin Endocrinol Metab 84: 1690–1694.

    Google Scholar 

  29. Zmuda JM, Cauley JA, Danielson ME, Theobald TM, Ferrell RE (1999) Vitamin D receptor translation initiation codon polymorphism and markers of osteoporotic risk in older African-American women. Osteoporosis Int 9: 214–219.

    Google Scholar 

  30. Minamitani K, Takahashi Y, Minagawa M, Yasuda T, Niimi H (1998) Difference in height associated with a translation start site polymorphism in the vitamin D receptro gene. Pediair Res 44: 628–632.

    Google Scholar 

  31. 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 

  32. Ma J, Stampfer MJ, Gann PH, et al. (1998) Vitamin D receptor polymorphisms, circulating vitamin D metabolites, and risk of prostate cancer in United States physicians. Cancer Epidemiol Biomarkers Prev 7: 385–390.

    Google Scholar 

  33. McClure L, Eccleshall TR, Gross C, et al. (1997) Vitamin D receptor polymorphisms, bone mineral density, and bone metabolism in postmenopausal Mexican-American women. J Bone Miner Res 12: 234–240.

    Google Scholar 

  34. Tokita A, Matsumoto H, Morrison NA, et al. (1996) Vitamin D receptor alleles, bone mineral density and turnover in premenopausal Japanese women. J Bone Miner Res 11: 1003–1009.

    Google Scholar 

  35. Williams CB, Bedenne L (1990) Management of colorectal polyps: is all the effort worthwhile? [Review]. J Gastroenterol Hepatol 5(Suppl. 1): 144–165.

    Google Scholar 

  36. Kim EC, Lance P (1997) Colorectal polyps and their relationship to cancer [Review]. Gastroenterol Clin N Am 26: 1–17.

    Google Scholar 

  37. Atkin WS, Morson BC, Cuzick J, et al. (1992) Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N Engl J Med 326: 658–662.

    Google Scholar 

  38. Saijo T, Ito M, Takeda E, et al. (1991) A unique mutation in the vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets type II: utility of single-strand conformation polymorphism analysis for heterozygous carrier detection. Am J Hum Genet 49: 668–673.

    Google Scholar 

  39. Miyamoto K, Kesterson RA, Yamamoto H, et al. (1997) Structural organization of the human vitamin D receptor chromosomal gene and its promoter. Mol Endocrinol 8: 1165–1179.

    Google Scholar 

  40. Gross C, Krishnan AV, Malloy PJ, Eccleshall TR, Zhao XY, Feldman D (1998) The vitamin D receptor gene start codon polymorphism: a functional analysis of FokI variants. J Bone Miner Res 13: 1691–1699.

    Google Scholar 

  41. Jurutka PW, Remus LS, Whitfield GK, et al. (2000) The polymorphic N terminus in human vitamin D receptor isoforms influences transcriptional activity by modulating interaction with transcription factor HB. Mol Endocrinol 14: 401–420.

    Google Scholar 

  42. Tajima O, Ashizawa N, Ishii T, et al. (2000) Interaction of the effects between vitamin D receptor polymorphism and exercise training on bone metabolism. J Appl Physiol 88: 1271–1276.

    Google Scholar 

  43. Ames SK, Ellis KJ, Gunn SK, Copeland KC, Abrams SA (1999) Vitamin D receptor gene Fok1 polymorphism predicts calcium absorption and bone mineral density in children. J Bone Miner Res 14: 740–746.

    Google Scholar 

  44. Hutchinson PE, Osborne JE, Lear JT, et al. (2000) Vitamin D receptor polymorphisms are associated with altered prognosis in patients with malignant melanoma. Clin Cancer Res 6: 498–504.

    Google Scholar 

  45. Wargovich MJ, Eng VW, Newmark HL (1984) Calcium inhibits the damaging and compensatory proliferative effects of fatty acids on mouse colon epithelium. Cancer Lett 23: 253–258.

    Google Scholar 

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Authors and Affiliations

  1. Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA

    Sue Ann Ingles, Jun Wang & Robert W. Haile

  2. Department of Urology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA

    Gerhard A. Coetzee

  3. Division of Gastroenterology, Bellflower Kaiser Permanente Medical Centers, Los Angeles, CA, USA

    Eric R. Lee

  4. Division of Gastroenterology, Sunset Kaiser Permanente Medical Centers, Los Angeles, CA, USA

    Harold D. Frankl

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  1. Sue Ann Ingles
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Ingles, S.A., Wang, J., Coetzee, G.A. et al. Vitamin D receptor polymorphisms and risk of colorectal adenomas (United States). Cancer Causes Control 12, 607–614 (2001). https://doi.org/10.1023/A:1011292002475

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