Cancer Causes & Control

, Volume 15, Issue 9, pp 863–872 | Cite as

Associations between BMI, energy intake, energy expenditure, VDR genotype and colon and rectal cancers (United States)

  • Martha L. SlatteryEmail author
  • Maureen Murtaugh
  • Bette Caan
  • Khe Ni Ma
  • Roger Wolff
  • Wade Samowitz


Components of energy balance are important elements associated with colorectal cancer risk. In this study we examine the association between VDR genotypes, BMI, physical activity, and energy intake and risk of colorectal cancer. Data from a population-based case–control study of colon (1174 cases and 1174 controls) and rectal (785 cases and 1000 controls) cancer was used to evaluate the associations. The Bsm1, polyA, and Fok1 VDR polymorphisms were evaluated. For colon cancer, those who are obese were at greater risk of colon cancer if they had the SS or BB (OR=3.50; 95 CI=1.75–7.03; p interaction 0.03) or ff (OR=2.62; 95 CI=1.15–5.99; p interaction 0.12/) VDR genotypes. On the other hand, those who were least physically active were at greater risk of colon cancer if they had theff VDR genotype (OR=3.46; 95 CI=1.58–7.58; p interaction 0.05. The association between energy intake and colon cancer appears to be driven more by energy intake than Bsm1 or polyA VDR genotypes, although there was a significant interaction between the Fok1 VDR polymorphism and energy intake and risk of both colon and rectal cancer (p interaction 0.01 for colon and 0.04 for rectal). These data suggest a relationship between VDR genotype and factors related to energy balance in modifying colorectal cancer risk.


BMI body size colorectal cancer energy balance energy expenditure energy intake physical activity VDR 



vitamin D receptor


restriction fragment length polymorphisms

3′ UTR I′

3 untranslated region


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Slattery, ML,  et al. 1997Energy balance and colon cancer–beyond physical activityCancer Res577580Google Scholar
  2. Caan, BJ,  et al. 1998Body size and the risk of colon cancer in a large case-control studyInt J Obes Relat Metab Disord22178184Google Scholar
  3. Martinez, ME 1997Leisure-time physical activity, body size, and colon cancer in women. Nurse’s Health Study Research GroupJ Natl Cancer Inst899489551997Google Scholar
  4. Giovannucci, E,  et al. 1995Physical activity, obesity, and risk for colon cancer and adenoma in menAnn Intern Med122327334Google Scholar
  5. Thun, MJ,  et al. 1992Risk factors for fatal colon cancer in a large prospective study.J Natl Cancer Inst8414911500Google Scholar
  6. Slattery, M.L,  et al. 2003Body mass index and colon cancer: an evaluation of the modifying effects of estrogen (United States)Cancer Causes Control147584Google Scholar
  7. Terry, PD, Miller, AB, Rohan, TE 2002Obesity and colorectal cancer risk in womenGut51191194Google Scholar
  8. Friedenreich, CM, Orenstein, MR 2002Physical activity and cancer prevention: etiologic evidence and biological mechanismsJ Nutr1323456S3464SSuppl 11Google Scholar
  9. Slattery, ML,  et al. 1997Physical activity and colon cancer: a public health perspectiveAnn Epidemiol7137145Google Scholar
  10. McTiernan, A,  et al. 1995Physical activity and cancer etiology: associations and mechanismsCancer Causes Control9487509Google Scholar
  11. Slattery, ML,  et al. 1997Dietary energy sources and colon cancer riskAm J Epidemiol145199210Google Scholar
  12. Willett, W, Stampfer, MJ 1986Total energy intake: implications for epidemiologic analysesAm J Epidemiol1241727Google Scholar
  13. Bostick, RM,  et al. 1994Sugar, meat, and fat intake, and non-dietary risk factors for colon cancer incidence in Iowa women (United States)Cancer Causes Control53852Google Scholar
  14. Kritchevsky, D,  et al. 1986Calories, fat and cancerLipids21272274Google Scholar
  15. Reddy, BS 1987Dietary fat and colon cancer: animal modelsPrev Med16460467Google Scholar
  16. Marchand, L,  et al. 1997Associations of sedentary lifestyle, obesity, smoking, alcohol use, and diabetes with the risk of colorectal cancerCancer Res5747874794Google Scholar
  17. Russo, A,  et al. 1998Body size and colorectal-cancer riskInt J Cancer78161165Google Scholar
  18. Adachi R, et al. (2003) Structural Determinants for Vitamin D Receptor Response to Endocrine and Xenobiotic Signals. Mol Endocrinol.Google Scholar
  19. Chokkalingam, AP,  et al. 2001Vitamin D receptor gene polymorphisms, insulin-like growth factors, and prostate cancer risk: a population-based case-control study in ChinaCancer Res6143334336Google Scholar
  20. Zeitz, U,  et al. 2003Impaired insulin secretory capacity in mice lacking a functional vitamin D receptorFASEB J17509511Google Scholar
  21. Chokkalingam, AP,  et al. 2001Vitamin D Receptor Gene Polymorphisms, Insulin-like Growth Factors, and Prostate Cancer Risk: A Population-based Case-Control Study in ChinaCancer Res6143334336Google Scholar
  22. Ingles, SA,  et al. 1997Strength of linkage disequilibrium between two vitamin D receptor markers in five ethnic groups: implications for association studiesCancer Epidemiol Biomarkers Prev69398Google Scholar
  23. Slattery, ML,  et al. 2001Variants of the VDR gene and risk of colon cancer (United States)Cancer Causes Control12359364Google Scholar
  24. Shakoori, AR,  et al. 1994Variations in vitamin D receptor transcription factor complexes associated with the osteocalcin gene vitamin D responsive element in osteoblasts and osteosarcoma cellsJ Cell Biochem55218229Google Scholar
  25. Staal, A,  et al. 1996Distinct conformations of vitamin D receptor/retinoid X receptor-alpha heterodimers are specified by dinucleotide differences in the vitamin D-responsive elements of the osteocalcin and osteopontin genesMol Endocrinol1014441456Google Scholar
  26. Kim, H.S,  et al. 2001Vitamin D receptor polymorphism and the risk of colorectal adenomas: evidence of interaction with dietary vitamin D and calciumCancer Epidemiol Biomarkers Prev10869874Google Scholar
  27. Ingles, SA,  et al. 2001Vitamin D receptor polymorphisms and risk of colorectal adenomas (United States)Cancer Causes Control12607614Google Scholar
  28. Wong, HL,  et al. 2003Vitamin D receptor start codon polymorphism and colorectal cancer risk: effect modification by dietary calcium and fat in Singapore ChineseCarcinogenesis2410911095Google Scholar
  29. Peters, U,  et al. 2001Vitamin D, calcium, and vitamin D receptor polymorphism in colorectal adenomasCancer Epidemiol Biomarkers Prev1012671274Google Scholar
  30. Tsuritani, I,  et al. 1998Does Vitamin D Receptor Polymorphism Influence the Response of Bone to Brisk Walking in Postmenopausal WomenHorm Res50315319Google Scholar
  31. Ortlepp, JR,  et al. 2003The vitamin D receptor gene variant and physical activity predicts fasting glucose levels in healthy young menDiabet Med20451454Google Scholar
  32. Ye, WZ,  et al. 2001Vitamin D receptor gene polymorphisms are associated with obesity in type 2 diabetic subjects with early age of onsetEur J Endocrinol145181186Google Scholar
  33. Edwards, S,  et al. 1994Objective system for interviewer performance evaluation for use in epidemiologic studiesAm J Epidemiol14010201028Google Scholar
  34. Slattery, ML,  et al. 1994A computerized diet history questionnaire for epidemiologic studiesJ Am Diet Assoc94761766Google Scholar
  35. McDonald, A,  et al. 1991The CARDIA dietary history: development, implementation, and evaluationJ Am Diet Assoc9111041112Google Scholar
  36. Liu, K,  et al. 1994A study of the reliability and comparative validity of the cardia dietary historyEthn Dis41527Google Scholar
  37. Ingles, SA,  et al. 1997Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptorJ Natl Cancer Inst89166170Google Scholar
  38. Curran, JE,  et al. 1999Association of A vitamin D receptor polymorphism with sporadic breast cancer developmentInt J Cancer83723726Google Scholar
  39. Hosmer, DW, Lemeshow, S 1992Confidence interval estimation of interactionEpidemiology3452456Google Scholar
  40. Slattery, ML,  et al. 1998NAT2, GSTM-1, cigarette smoking, and risk of colon cancerCancer Epidemiol Biomarkers Prev710791084Google Scholar
  41. Steinbach, G,  et al. 1993Effects of caloric restriction and dietary fat on epithelial cell proliferation in rat colonCancer Res5327452749Google Scholar
  42. Gerber, M, Corpet, D 1999Energy balance and cancersEur J Cancer Prev87789Google Scholar
  43. Kaaks, R, Lukanova, A 2001Energy balance and cancer: the role of insulin and insulin-like growth factor-IProc Nutr Soc6091106Google Scholar
  44. Nanda, K,  et al. 1999Hormone replacement therapy and the risk of colorectal cancer: a meta-analysisObstet Gynecol93880888Google Scholar
  45. Giovannucci, E 1999Insulin-like growth factor-I and binding protein-3 and risk of cancerHorm Res513441Suppl 3Google Scholar
  46. Ma, J,  et al. 2000A prospective study of plasma levels of insulin-like growth factor I (IGF-I) and IGF-binding protein-3, and colorectal cancer risk among menGrowth Horm IGF Res10S28S29Suppl AGoogle Scholar
  47. Sandhu, MS, Dunger, DB, Giovannucci, EL 2002Insulin, insulin-like growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancerJ Natl Cancer Inst94972980Google Scholar
  48. Hansen, BC 1995Obesity, diabetes, and insulin resistance: implications from molecular biology, epidemiology, and experimental studies in humans and animals. Synopsis of the American Diabetes Association’s 29th Research Symposium and Satellie Conference of the 7th International Congress on Obesity, Boston, Massachusets.Diabetes Care18A2A9Google Scholar
  49. Bonadonna, RC,  et al. 1990Obesity and insulin resistance in humans: a dose-response studyMetab39452459Google Scholar
  50. Ogunkolade, BW,  et al. 2002Vitamin D receptor (VDR) mRNA and VDR protein levels in relation to vitamin D status, insulin secretory capacity, and VDR genotype in Bangladeshi AsiansDiabetes5122942300Google Scholar
  51. Barger-Lux, MJ,  et al. 1995Vitamin D receptor gene polymorphism, bone mass, body size, and vitamin D receptor densityCalcif Tissue Int57161162Google Scholar
  52. Tsuritani, I,  et al. 1998Does vitamin D receptor polymorphism influence the response of bone to brisk walking in postmenopausal womenHorm Res50315319Google Scholar
  53. Slattery, ML,  et al. 2004Dietary calcium, vitamin D, VDR genotypes and colorectal cancerInt J Cancer111750756Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Martha L. Slattery
    • 1
    • 2
    Email author
  • Maureen Murtaugh
    • 1
  • Bette Caan
    • 3
  • Khe Ni Ma
    • 1
  • Roger Wolff
    • 1
  • Wade Samowitz
    • 4
  1. 1.Health Research CenterUniversity of UtahSalt Lake CityUtah
  2. 2.Department of Family and Health Research CenterPreventive MedicineSalt Lake CityUS
  3. 3.Kaiser Permanente Medical Research ProgramOaklandCalifornia
  4. 4.Department of Surgical PathologyUniversity of UtahSalt Lake CityUtah

Personalised recommendations