Source: UNIVERSITY OF ARIZONA submitted to NRP
THE ROLE OF CAROTENOID-RICH VEGETABLES, CRUCIFEROUS VEGETABLES AND CITRUS FRUIT IN REDUCING OXIDATIVE DAMAGE AMONG BREAST CANCER SURVIVORS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
0192764
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Jul 1, 2002
Project End Date
Sep 30, 2006
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
UNIVERSITY OF ARIZONA
888 N EUCLID AVE
TUCSON,AZ 85719-4824
Performing Department
NUTRITIONAL SCIENCES
Non Technical Summary
Diets low in fruits and vegetables may increase oxidative damage leading to higher breast cancer recurrence rates among breast cancer survivors. The purpose of this study is to determine if a high fruit and vegetable diet can reduce oxidative damage among women previously treated for breast cancer.
Animal Health Component
75%
Research Effort Categories
Basic
25%
Applied
75%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
70260101010100%
Goals / Objectives
Study objectives: To assess baseline, year one and four dietary intake of carotenoids, cruciferous vegetables and citrus fruit among breast cancer survivors participating in the WHEL study. To measure biological levels of carotenoids in plasma from subjects. To measure urinary and blood levels of oxidative damage biomarkers, including 8-hydroxydeoxyguanasine, 8-epiprostaglandin and the COMET assay in study subjects. To correlate dietary intake with levels of oxidative damage Overview/Description of the Study This research is an ancillary study in a randomized, prospective, controlled multi-center clinical trial investigating the role of a diet high in vegetables, fruit and low in dietary fat in altering oxidative damage, a possible precursor of breast cancer recurrence. The research is a sub-study of the WHEL study established to investigate the effect of a high vegetable and fruit, low fat, high fiber diet on breast cancer recurrence. The study will focus on short-term biological markers of oxidative damage which may mediate the effects of the intervention on breast cancer recurrence. Specifically, this study will measure urinary OhdG and EPG levels and the COMET assay in breast cancer survivors and describe the association between intake of carotenoids, cruciferous vegetables and citrus fruit and oxidative damage biomarkers.
Project Methods
Plasma samples will be collected at baseline, years one and four. Analysis of plasma carotenoids will be performed by Dr. Cheryl Rock, PhD,RD at the University of California San Diego and include b-carotene, a-carotene, lutein/zeaxanthin, lycopene and b-cryptoxanthin. Plasma carotenoids are separated and quantified with HPLC methodology using a Varian Star 9010, 9050 system. For each sample designated for carotenoid analysis, determinations of total plasma cholesterol concentrations are performed with the Kodak Ektachem Analyzer system. Urine samples will be collected at baseline, years one and four. Each participant will be instructed on sample collection procedures. All urine excreted during the first a.m. void will be collected and will be transported to the study clinic within 2 hours of collection. The urine will be gently mixed and separated into four separate 2 ml aliquotes for oxidative biomarker analysis. Samples will be stored at -80C. Frozen samples will be thawed at room temperature and then analyzed for oxidative damage biomarkers. Body Composition: Height, weight, waist-hip ratio and body composition will be measured on each participant at baseline, year one and four. Body composition will be measured using the Body Composition Analyzer available from Valhala Scientific and will include percent body fat, percent lean body mass, kilograms body fat and kilograms lean body mass, percent body water. All measurements will be taken following an overnight fast. Body composition is used to standardize oxidative damage biomarkers. Dietary recalls and Food Frequency data will be collected from all study participants at baseline and one year. Recalls will be completed by trained dietary assessors from the WHEL study Coordinating Center in San Diego, CA. Participants will be asked to recall intake for four separate days over a three-week time period. Dietary intake will be evaluated for nutrients, carotenoids, macronutrients and food groups using the NDS Nutrient Analysis database. Statistical analysis: to test the hypotheses for this research the following statistical analyses will be performed. 1) Descriptives of study population 2) Descriptives of dietary intake, plasma carotenoids and oxidative damage biomarkers. 3) T-test of change in diet, carotenoids and oxidative damage by treatment group at the years one and four. 4) Correlational analyses to determine if significant associations exist between dietary intake, plasma carotenoid levels and oxidative damage.

Progress 07/01/02 to 09/30/06

Outputs
Termination Report: This research has focused on the role of diet and specific dietary constituents in reducing oxidative stress among women at risk for breast cancer recurrence. To date we have been able to assess intake of diet and the specific dietary constituents of interest -fruit/vegetables, cruciferous vegetables and citrus as well as to analyze urine samples for oxidative stress in a sub-group of these women and plasma carotenoid levels in a separate subgroup. Our findings suggest that while the intervention diet used in the women's healthy eating and living study resulted in a significant increase in fruit and vegetable intake, including cruciferous vegetable intake AND this increase in plant foods (Thomson, 2007;Newman, Thomson, 2005 and Thomson, in press, 2007) also resulted in significantly increased plasma carotenoid levels (Rock, Thomson, 2003), no significant reduction in oxidative stress was shown over time (Thomson, 2005). Recent analysis testing the association between plasma carotenoids and oxidative stress in the WHEL women also shows that women in the highest quartile of plasma alpha and beta carotene as well as total carotenoids demonstrate significantly lower levels of oxidant stress as compared to those in the lowest quartile. Dietary carotenoids were generally not significantly associated with oxidant stress. We have previously published findings indicating that increased total plasma carotenoid values are associated with significantly reduced risk for breast cancer recurrence (Rock, 2005), and our recent findings suggest that reduction in oxidant stress may be contributing to this protective association.

Impacts
This research provides evidence for clinicians caring for breast cancer survivors and breast cancer survivors themselves to suggest that behavioral change toward a diet high in carotenoidscan reduce oxidative stress and reduce recurrence of breast cancer among women previously treated for this disease.

Publications

  • Thomson CA, Rock CL, Caan BJ, Flatt SW, Al-Delaimy WA, Newman VA, Hajek RA, Chilton RJ, Pierce JP. Increase in Cruciferous Vegetable Intake in Women Previously Treated for Breast Cancer Participating in a Dietary Intervention Trial. Nutrition and Cancer 2006 (Accepted).
  • Thomson CA, Newton TR, Graver EJ, Jackson K, Reid PM, Hartz VL, Cussler EC, Hakim IA. Cruciferous Vegetable Intake Questionnaire Improves Cruciferous Vegetable Intake Estimates. Journal of the American Dietetic Association. (In press, March 2007).
  • Newman V, Thomson CA, Rock CL, Flatt SW, Kealey S, Bardwell WA, Caan BJ, Pierce JP. Achieving Substantial Changes in Eating Behavior Among Women Previously Treated for Breast Cancer: An Intervention Overview. Journal of the American Dietetic Association, 105(3): 382-391, 2005
  • Thomson CA, Rock CS, Giuliano A, Newton TR, Cui Haiyan, Green TL and Alberts DS. Longitudinal changes in body weight and body composition among women at risk for breast cancer recurrence consuming a high-vegetable, fruit and fiber, low fat diet. European Journal of Nutrition, 44: 18-25, 2005.
  • Thomson CA, Giuliano AR, Shaw J, Rock CL, Ritenbaugh CK, Hakim IA, Hollenbach KA, Childs J, Alberts DS and Pierce, JP. Diet and Biomarkers of Oxidative Damage in Women previously treated for Breast Cancer. Nutrition and Cancer, 51(2): 146-155, 2005.
  • Rock CS, Flatt SW, Natarajan L, Thomson CA, Bardwell WA, Newman VA, Hollenbach KA, Jones L, Caan BJ, Pierce JP. Plasma carotenoids and recurrence-free survival in women with a history of breast cancer. Journal of Clinical Oncology, 23(27): 6631-6638, 2005
  • Pierce JP, Newman VA, Flatt SW, Faerber S, Rock CL, Natarajan L, Caan BJ, Gold EB, Hollenbach KA, Wasserman L, Jones L, Ritenbaugh C, Stefanick ML, Thomson CA and Kealey. Telephone Counseling Intervention Increases Intakes of Micronutrients and Phytochemical-Rich Vegetables, Fruit and Fiber in Breast Cancer Survivors. Journal of Nutrition, 134(2): 452-458, 2004
  • Thomson CA, Flatt SW, Rock CL, Ritenbaugh C, Newman V, Pierce JP. Increased fruit, vegetable and fiber intake and lower fat intake reported among women previously treated for invasive breast cancer. Journal of American Dietetic Association, 102(6): 801-808, 2002


Progress 01/01/05 to 12/31/05

Outputs
This research has focused on the role of diet and specific dietary constituents in reducing oxiative stress among women at risk for breast cancer recurrence. To date we have been able to assess intake of diet and the specific dietary constituents of interest -fruit/vegetables, cruciferous vegetables and citrus as well as to analyze urine samples for oxidative stress in a sub-group of these women and plasma carotemoind levels in a separate sub-group. Our findings suggest that while the intervention diet used in the women's healthy eating and living study resulted in a signigicanft increase in fruit and vegetable intake, including cruciferous vegetable intake AND this increase in plant foods (Newman, Thomson, 2005) also resulted in significantly increased plasma carotenoid levels (Rock, Thomson, 2003), no significant reduction in oxidative stress was shown over time (Thomson, 2005). Recent analysis testing the association between plasma carotenoids and oxidative stress in the WHEL women also shows no significant association and a null paper is under development. However, recently we published findings indicating that increased total plasma carotenoid values are associated with significantly improved hazard ratio for recurrence of breast cancer among thw WHEL study subjects randomly assigned to the control group.

Impacts
This research provides evidence that while fruit/vegetable and plasma carotenoid values may be significantly increased in response to participation in a dietary intervention trial that provides significant support for dietary behavior change, this "healthy volunteer" population of breast cancer survivors showed low levels of oxidative stress at baseline and these levels were not significantly changed with the significant increase in antioxidant-rich foods.

Publications

  • Thomson CA, Harris RB, Craft NE Hakim IA A cross-sectional analysis demonstrated the healthy volunteer effect in smokers. Journal of Clinical Epidemiology, 58: 378-382, 2005.
  • Newman V, Thomson CA, Rock CL, Flatt SW, Kealey S, Bardwell WA, Caan BJ, Pierce JP. Achieving Substantial Changes in Eating Behavior Among Women Previously Treated for Breast Cancer: An Intervention Overview. Journal of the American Dietetic Association, 105(3): 382-391, 2005
  • Thomson CA, Rock CS, Giuliano A, Newton TR, Cui Haiyan, Green TL and Alberts DS. Longitudinal changes in body weight and body composition among women at risk for breast cancer recurrence consuming a high-vegetable, fruit and fiber, low fat diet. European Journal of Nutrition, 44: 18-25, 2005.
  • Thomson CA, Giuliano AR, Shaw J, Rock CL, Ritenbaugh CK, Hakim IA, Hollenbach KA, Childs J, Alberts DS and Pierce, JP. Diet and Biomarkers of Oxidative Damage in Women previously treated for Breast Cancer. Nutrition and Cancer, 51(2): 146-155, 2005.
  • Rock CS, Flatt SW, Natarajan L, Thomson CA, Bardwell WA, Newman VA, Hollenbach KA, Jones L, Caan BJ, Pierce JP. Plasma carotenoids and recurrence-free survival in women with a history of breast cancer. Journal of Clinical Oncology, 23(27): 6631-6638, 2005
  • Thomson CA, Newton T, Jackson K, Reid P, Hakim I. Use of a validated cruciferous vegetable food frequency questionnaire to improve measurement of cruciferous vegetables intake. Journal Amer Dietetic Assoc, 2006 (in press).
  • Pierce JP, Newman VA, Flatt SW, Faerber S, Rock CL, Natarajan L, Caan BJ, Gold EB, Hollenbach KA, Wasserman L, Jones L, Ritenbaugh C, Stefanick ML, Thomson CA and Kealey. Telephone Counseling Intervention Increases Intakes of Micronutrients and Phytochemical-Rich Vegetables, Fruit and Fiber in Breast Cancer Survivors. Journal of Nutrition, 134(2): 452-458, 2004
  • Rock CL, Thomson CA, Caan BJ, Flatt SW, Newman V, Ritenbaugh C, Marshall JR, Hollenbach KA, Stefanick ML, Pierce JP. Reduction in fat intake is not associated with weight loss in most women after breast cancer diagnosis: Evidence from a randomized controlled trial. Cancer, 91(1): 25-34, 2001.
  • Thomson CA, Flatt SW, Rock CL, Ritenbaugh C, Newman V, Pierce JP. Increased fruit, vegetable and fiber intake and lower fat intake reported among women previously treated for invasive breast cancer. Journal of American Dietetic Association, 102(6): 801-808, 2002


Progress 01/01/04 to 12/31/04

Outputs
The objectives of this research are to: 1. Assess baseline, year 1 and year 4 dietary intake of carotenoids, cruciferous vegetables and citrus fruit among breast cancer survivors participating in the Womens Health Eating and Living Study. 2. Measure biological levels of carotenoids in serum in a sub-sample of WHEL study participants. 3. Measure urinary and blood levels of oxidative damage biomarkers including 8-hydroxy-2-deoxy-guanasine, 8-epi-prostaglandin-F-2-alpha and the COMET assay in a sub-sample of WHEL subjects. 4. Correlate dietary intake with levels of oxidative damage among WHEL study subjects including analysis of potential confounding factors such as dietary supplement use, alcohol intake and levels of physical activity. To date, baseline, year 1 and year 4 data have been collected and biological samples for urinary oxidative damage biomarkers and serum carotenoids have been analyzed for baseline and year 1. Year 4 samples will be analyzed for oxidative damage and carotenoid values during 2005-2006 grant year. A publication summarizing the findings regarding changes in oxidative damage from baseline to year 1 has been accepted by the journal Nutrition and Cancer. Of note, the level of oxidative damage in this study sample, even at baseline, was well below reported levels for other study populations reported in the literature. Dietary vitamin E was associated with a decrease in 8-epiprostaglandin F2-alpha and arachidonic acid intake was associated with increased 8-hydroxy-deoxyguanasine levels. A second analysis looking at associations between serum carotenoid levels and oxidative damage at baseline and year 1 is currently underway and a publication will be submitted during this next report period. In addition, a validated instrument to collect cruciferous vegetable intake data has been developed for use in this project and it along with a previously developed citrus intake questionnaire are currently being administered by mail to the breast cancer survivors at seven research sites participating in the Womens Healthy Eating and Living Study. To date the average response rate for the first mailing is 62%; a second mailing of the questionnaires is scheduled for this spring in an effort to increase the response rate by an additional 10 to 15%.

Impacts
This research will provide additional evidence of the potential health benefits of dietary carotenoids, specifically for women previuosly treated for breast cancer.

Publications

  • Thomson CA, Giuliano AR, Shaw J, Rock CL, Ritenbaugh CK, Hakim IA, Hollenbach KA, Childs J, Alberts DS and Pierce, JP.(2005) Diet and Biomarkers of Oxidative Damage in Women previously Treated for Breast Cancer. Nutrition and Cancer, vol 51(2) (accepted)
  • Newman V, Thomson CA, Rock CL, Flatt SW, Kealey S, Bardwell WA, Caan BJ, Pierce JP. (2005) Achieving Substantial Changes in Eating Behavior Among Women Previously Treated for Breast Cancer: An Intervention Overview. J Amer Dietetic Assoc 105:382-391.


Progress 01/01/03 to 12/31/03

Outputs
The objectives of this research are to: 1. Assess baseline, year 1 and year 4 dietary intake of carotenoids, cruciferous vegetables and citrus fruit among breast cancer survivors participating in the Women's Health eating and Living Study. 2. Measure biological levels of carotenoids in serum in a sub-sample of WHEL study participants. 3. Measure urinary and blood levels of oxidative damage biomarkers - including 8-hydroxy-2'-deoxy-guanasine, 8-epi-prostaglandin-F-2-alpha and the COMET assay in a sub-sample of WHEL subjects. 4. Correlate dietary intake with levels of oxidative damage among WHEL study subjects including analysis of potential confounding factors such as dietary supplement use, alcohol intake and levels of physical activity. To date, baseline and year 1 data have been collected and biological samples for urinary oxidative damage biomarkers and serum carotenoids have been analyzed. Year 4 samples are currently being collected. The first paper focused on the change in oxidative damage from baseline to one year shows a non-significant decrease in damage over 12 months for the total study sample, even when analyzed for level of adherence to a cancer-preventive eating pattern. Of note, the level of oxidative damage in this study sample, even at baseline, was well below reported levels for other study populations reported in the literature. Factors associated with change in oxidative damage included age and use of vitamin E supplements. This paper will be submitted to the Journal of Nutrition in the Spring of 2004. A second analysis looking at associations between serum carotenoid levels and oxidative damage at baseline and year 1 is currently underway and a publication will be submitted during this next report period.

Impacts
This research will provide additional evidence of the potential health benefits of dietary carotenoids, specifically for women previuosly treated for breast cancer.

Publications

  • No publications reported this period


Progress 01/01/02 to 12/31/02

Outputs
The objectives of this research are to:1.To assess baseline, year 1 and year 4 dietary intake of carotenoids, cruciferous vegetables and citrus fruit among breast cancer survivors participating in the WHEL study. 2.To measure biological levels of carotenoids in serum of a sub-sample of WHEL study subjects.3.To measure urinary and blood levels of oxidative damage biomarkers -including 8-hydroxy-2'-deoxy-guanasine, 8-epiprostaglandin -F-2'a and the COMET assay in a sub-sample of WHEL study subjects.4.To correlate dietary intake with levels of oxidative damage among WHEL study subjects including analyses of potential confounding factors such as dietary supplement use, alcohol intake and levels of physical activity. To date, baseline and year one dietary data and biological samples have been collected on 187 breast cancer survivors participating in the WHEL study. Plasma carotenoid analysis is currently underway using samples collected at these same time points. In addition, dietary data has been cleaned and is currently being analyzed. Data to explore confounding variables, including physical activity, age, ethnicity., compliance level, dietary supplement use are also being placed in the statistical model to determine significant associations. Urinary analysis for oxidative damamge biomarkers including 8OHdG and 8epi-prostaglandinF2-alpha have also been completed for the baseline and twelve month data sets.

Impacts
This research will provide insight into the potential use of dietary modulation in reducing oxidative damage, a proposed risk factor for breast cancer recurrence.

Publications

  • No publications reported this period