RANDOMIZED TRIAL OF FOLATE AND COLORECTAL ADENOMA

Summary

Principal Investigator: Edward L Giovannucci
Abstract: Given the high rates of colorectal cancer and the potential chemopreventive properties of folate or folic acid, it is crucial to demonstrate in a randomized setting that folic acid supplementation reduces the occurrence of colorectal neoplasia. We thus propose to continue to examine the hypothesis that folic acid supplementation of 1,000 micrograms daily will reduce the recurrence rate of colorectal adenomas, precursors of cancers using a randomized, placebo-controlled intervention trial. This study has been successfully initiated and has been ongoing since 1996 among 750 individuals within two ongoing cohort studies, the Health Professionals Follow-Up Study and the Nurses' Health Study. As planned, we will examine whether any influence of folate is modified by various factors, including baseline folate and vitamin B12 levels, aspirin use, family history of colorectal cancer, and intakes of alcohol and methionine. For this submission, we now propose extending follow-up from three to five years because of recent evidence of a long induction period between folate intake and colorectal cancer, and because recent fortification of food products with folic acid may reduce the contrast of folate status between intervention and placebo groups. We further propose to measure additional folate- related factors (plasma homocysteine, methylene-tetrahydrofolate reductase (MTHFR) genotype) and insulin-like growth factor (IGF) parameters (insulin-like growth factor-1 and insulin-like growth factor binding protein-3), which we have found to be the strongest cluster of etiologic factors for colorectal carcinogenesis in our cohorts. Thus, it is of interest to examine the independent and interacting roles of folate-related and IGF-related factors in adenoma recurrence. Within our existing cohorts, the intervention trial, as well as the proposed additional biomarker and genotype measures, can be conducted at a fraction of the cost of a similarly sized intervention trial of colorectal adenoma recurrence in other typical settings.
Funding Period: 1995-09-15 - 2005-02-28
more information: NIH RePORT

Top Publications

  1. pmc Application of the Rosner-Colditz risk prediction model to estimate sexual orientation group disparities in breast cancer risk in a U.S. cohort of premenopausal women
    S Bryn Austin
    Division of Adolescent and Young Adult Medicine, Children s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 21:2201-8. 2012
  2. pmc An examination of sexual orientation group patterns in mammographic and colorectal screening in a cohort of U.S. women
    S Bryn Austin
    Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Cancer Causes Control 24:539-47. 2013
  3. pmc The mediating effect of childhood abuse in sexual orientation disparities in tobacco and alcohol use during adolescence: results from the Nurses' Health Study II
    Hee Jin Jun
    Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Cancer Causes Control 21:1817-28. 2010
  4. pmc Adult body mass index trajectories and sexual orientation: the Nurses' Health Study II
    Hee Jin Jun
    Channing Laboratory, Brigham and Women s Hospital Harvard Medical School, Boston, Massachusetts, USA
    Am J Prev Med 42:348-54. 2012
  5. pmc Folic acid and prevention of colorectal adenomas: a combined analysis of randomized clinical trials
    Jane C Figueiredo
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
    Int J Cancer 129:192-203. 2011
  6. pmc A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma
    Kana Wu
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Am J Clin Nutr 90:1623-31. 2009
  7. pmc Caffeinated and alcoholic beverage intake in relation to ovulatory disorder infertility
    Jorge E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
    Epidemiology 20:374-81. 2009
  8. pmc Disparities in child abuse victimization in lesbian, bisexual, and heterosexual women in the Nurses' Health Study II
    S Bryn Austin
    Division of Adolescent and Young Adult Medicine, Children s Hospital, Boston, Massachusetts 02115, USA
    J Womens Health (Larchmt) 17:597-606. 2008
  9. pmc Postmenopausal hormone therapy and stroke: role of time since menopause and age at initiation of hormone therapy
    Francine Grodstein
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 181 Longwood Ave, Boston, Massachusetts 02115, USA
    Arch Intern Med 168:861-6. 2008
  10. pmc Protein intake and ovulatory infertility
    Jorge E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Am J Obstet Gynecol 198:210.e1-7. 2008

Scientific Experts

  • J E Chavarro
  • Clement A Adebamowo
  • Kana Wu
  • S Bryn Austin
  • Francine Grodstein
  • Hee Jin Jun
  • Donna Spiegelman
  • Mathew J Pazaris
  • Heather L Corliss
  • Jane C Figueiredo
  • Patricia Case
  • Lauren P Nichols
  • Leila A Mott
  • Matthew J Grainge
  • Edward Giovannucci
  • John A Baron
  • Bernard Cole
  • Richard F Logan
  • Sarah A Wylie
  • Rosalind J Wright
  • Benita Jackson
  • David J Hunter
  • JoAnn E Manson
  • Susan Malspeis
  • Walter C Willett

Detail Information

Publications19

  1. pmc Application of the Rosner-Colditz risk prediction model to estimate sexual orientation group disparities in breast cancer risk in a U.S. cohort of premenopausal women
    S Bryn Austin
    Division of Adolescent and Young Adult Medicine, Children s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 21:2201-8. 2012
    ..Lesbian and bisexual women may be at greater risk of breast cancer than heterosexual women during the premenopausal period due to disparities in risk factors...
  2. pmc An examination of sexual orientation group patterns in mammographic and colorectal screening in a cohort of U.S. women
    S Bryn Austin
    Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Cancer Causes Control 24:539-47. 2013
    ..Underutilization of cancer screening has been found especially to affect socially marginalized groups. We investigated sexual orientation group patterns in breast and colorectal cancer screening adherence...
  3. pmc The mediating effect of childhood abuse in sexual orientation disparities in tobacco and alcohol use during adolescence: results from the Nurses' Health Study II
    Hee Jin Jun
    Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Cancer Causes Control 21:1817-28. 2010
    ..To examine the mediating effect of childhood abuse on sexual orientation disparities in tobacco and alcohol use during adolescence...
  4. pmc Adult body mass index trajectories and sexual orientation: the Nurses' Health Study II
    Hee Jin Jun
    Channing Laboratory, Brigham and Women s Hospital Harvard Medical School, Boston, Massachusetts, USA
    Am J Prev Med 42:348-54. 2012
    ..Cross-sectional research has documented elevated prevalence of obesity in lesbian and bisexual women relative to heterosexual women, but little is known about disparities in longitudinal patterns in BMI change during adulthood...
  5. pmc Folic acid and prevention of colorectal adenomas: a combined analysis of randomized clinical trials
    Jane C Figueiredo
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
    Int J Cancer 129:192-203. 2011
    ..7% vs. 0.5%, p = 0.002). In conclusion, after up to 3.5 years of folic acid use, there is no clear decrease or increase in the occurrence of new adenomas in patients with a history of adenoma...
  6. pmc A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma
    Kana Wu
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Am J Clin Nutr 90:1623-31. 2009
    ..Evidence from observational studies suggests that inadequate folate status enhances colorectal carcinogenesis, but results from some randomized trials do not support this hypothesis...
  7. pmc Caffeinated and alcoholic beverage intake in relation to ovulatory disorder infertility
    Jorge E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
    Epidemiology 20:374-81. 2009
    ..However, most of these studies have retrospectively collected information on alcohol and caffeine intake, making the results susceptible to biases...
  8. pmc Disparities in child abuse victimization in lesbian, bisexual, and heterosexual women in the Nurses' Health Study II
    S Bryn Austin
    Division of Adolescent and Young Adult Medicine, Children s Hospital, Boston, Massachusetts 02115, USA
    J Womens Health (Larchmt) 17:597-606. 2008
    ..One underlying factor may be heightened risk for abuse victimization in childhood in lesbian and bisexual women...
  9. pmc Postmenopausal hormone therapy and stroke: role of time since menopause and age at initiation of hormone therapy
    Francine Grodstein
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 181 Longwood Ave, Boston, Massachusetts 02115, USA
    Arch Intern Med 168:861-6. 2008
    ..We evaluated stroke risk associated with hormone therapy (HT) in younger women, in recently menopausal women, and in older women...
  10. pmc Protein intake and ovulatory infertility
    Jorge E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Am J Obstet Gynecol 198:210.e1-7. 2008
    ..The objective of the study was to evaluate whether intake of protein from animal and vegetable origin is associated with ovulatory infertility...
  11. ncbi Diet and lifestyle in the prevention of ovulatory disorder infertility
    Jorge E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston MA 02115, USA
    Obstet Gynecol 110:1050-8. 2007
    ..To evaluate the relation of a dietary pattern and other lifestyle practices to risk of ovulatory disorder infertility...
  12. pmc A prospective study of dietary carbohydrate quantity and quality in relation to risk of ovulatory infertility
    J E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Eur J Clin Nutr 63:78-86. 2009
    ..To evaluate whether the amount or quality of carbohydrate in diet is associated with ovulatory infertility...
  13. pmc Use of multivitamins, intake of B vitamins, and risk of ovulatory infertility
    Jorge E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Fertil Steril 89:668-76. 2008
    ..To examine whether use of multivitamins and intake of specific nutrients in multivitamins is associated with ovulatory infertility...
  14. ncbi A prospective study of dairy foods intake and anovulatory infertility
    J E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Hum Reprod 22:1340-7. 2007
    ..Yet, few studies have been conducted in humans and their results are inconsistent. We evaluated whether intake of dairy foods was associated with anovulatory infertility and whether this association differed according to fat content...
  15. ncbi Dietary fatty acid intakes and the risk of ovulatory infertility
    Jorge E Chavarro
    Department of Nutrition, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Am J Clin Nutr 85:231-7. 2007
    ..Pharmacologic activation of the peroxisome proliferator-activated receptor gamma (PPAR-gamma) improves ovulatory function in women with polycystic ovary syndrome, and specific dietary fatty acids can affect PPAR-gamma activity...
  16. ncbi Iron intake and risk of ovulatory infertility
    Jorge E Chavarro
    Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Obstet Gynecol 108:1145-52. 2006
    ..To evaluate whether iron supplement use or greater intake of total, heme and nonheme iron is associated with lower risk of ovulatory infertility...
  17. ncbi Disclosure of sexual orientation and behavior in the Nurses' Health Study II: results from a pilot study
    Patricia Case
    Fenway Institute, Fenway Community Health, Boston MA 02115, USA
    J Homosex 51:13-31. 2006
    ..To examine disclosure of sexual orientation and response rates in a pilot study of questions on sexual orientation and gender of sexual partners in the Nurses' Health Study II...
  18. ncbi High school dietary dairy intake and teenage acne
    Clement A Adebamowo
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    J Am Acad Dermatol 52:207-14. 2005
    ..We examined data from the Nurses Health Study II to retrospectively evaluate whether intakes of dairy foods during high school were associated with physician-diagnosed severe teenage acne...
  19. ncbi Dietary flavonols and flavonol-rich foods intake and the risk of breast cancer
    Clement A Adebamowo
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Int J Cancer 114:628-33. 2005
    ..76 (0.57, 1.00; p-value for test of trend=0.03). While we found no overall association between intake of flavonols and risk of breast cancer, there was an inverse association with intake of beans or lentils that merits further evaluation...