Nutritional Intervention and DNA Damage of Patients With HBOC

Effects of a Nutritional Intervention in DNA Damage of Patients With Hereditary Breast and Ovarian Cancer Syndrome

Breast and Ovarian Cancer Syndrome (HBOC) is characterized by mutations in tumor suppressor genes such as BRCA1 and BRCA2, which increase the carrier's risk of developing breast and ovarian cancer, especially before 40. In this pathology the DNA damage is increased because there is a state of chronic inflammation, plus the antineoplastic treatments and changes in body composition result in oxidative stress. The inductions of epigenetic changes by a nutritional intervention with an specific distribution of macronutrients, micronutrients and polyphenols, not only ensures an optimal nutritional status, but also shows a decrease in oxidative stress, and therefore in DNA damage. The aim of this study is to assess if the DNA damage in patients with HBOC decreases after the nutritional intervention.

Study Overview

• Status: Completed
• Conditions: DNA Damage; Nutrition Therapy; HBOC Syndrome
• Intervention / Treatment: Combination product: Antioxidant therapy

Detailed Description

Breast and Ovarian Cancer Syndrome (HBOC) is a genetic disease characterized by mutations in tumor suppressor genes such as BRCA1 and BRCA2, elevation of Reactive Oxygen Species (ROS), inflammation and DNA damage; all this as a result of the pathology itself. Antineoplastic treatments and changes in body composition such as malnutrition, cachexia and obesity lead to an increase of the inflammatory state. The induction of epigenetic changes by a nutritional intervention suggests that an hypo caloric diet, complex carbohydrates, polyunsaturated fatty acids, some amino acids, and some vitamins, minerals and polyphenols as well, can reduce DNA damage because of the interaction between mechanisms related with DNA stability and reparation, cellular replication, induction of apoptosis, and antioxidant systems. Previous studies report that using polyphenols supplements can reduce de DNA damage, but when the administration is only through food there's no benefit at all. So the aim of this study is to assess if the use of different micronutrients and polyphenols in conjoint can make synergism and reduce de DNA damage without the need of supplements.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Benito Juárez
    • Mexico City, Benito Juárez, Mexico, 03420
      • María Fernanda Díaz Yáñez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female patients diagnosed with HBOC according to the Mexican Consensus of Breast Cancer
• Patients over 18 years who voluntarily agree to participate in the study and sign the informed consent.

Exclusion Criteria:

• Patients with end-stage chronic kidney failure, heart failure, liver failure, rheumatoid arthritis, non-inherited AC or HIV.
• Patients who carry out a structured exercise plan (rehabilitation) at the time of inclusion in the study.
• Patients who carry out a structured eating plan (adherence to diet) or who are consuming a food supplement at the time of inclusion in the study.
• Patients with significant primary clinical disorders: hematological (hemoglobin <13 in men and <12 in women), renal (creatinine> 3), neurological (other than epilepsy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Antioxidant therapy; The patient will get a nutritional personalized treatment with the following characteristics: hypocaloric diet, rich in micronutrients related with DNA reparation and polyphenols, with the next distribution: 45% carbohydrates, 30% lipids, 25% protein, <10% saturated fats, >10% unsaturated fats, based on the recommendations of the American Institute for Cancer Research (AICR).

Combination product: Antioxidant therapy; Antioxidant therapy based in the following dietary components: Zinc, Selenium, Magnesium, carotenoids, indole-3-carbinol, curcumin, epigalactocatechin, caffeine, resveratrol, lycopene, genistein, phytoestrogens

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNA damage change	A blood sample will be taken to assess DNA damage (ELISA) by 8-hydroxy-2-deoxyguanosine (8-OHdG), a modified nitrogen base indicating oxidative damage to DNA, before and after nutritional intervention.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body composition change	A bioelectrical impedance analysis will be used to assess the body composition through the reactance and resistance values (both measured in Ohm), before and after nutritional intervention.	12 weeks
Muscular strength change	A hand grip dynamometer will be used to assess the muscular strength in kg, both before and after the nutritional intervention.	12 weeks
Dietary change: Energy	A 24-hour recalls will be performed to evaluate amount of energy (measured in kilocalories), before and after the nutritional intervention.	12 weeks
Dietary change: Macronutrients	A 24-hour recalls will be performed to evaluate amount of carbohydrate, protein and fat (all measured in percentage and grams), before and after the nutritional intervention.	12 weeks
Dietary change: Micronutrients	A 24-hour recalls will be performed to evaluate amount of vitamin E, calcium, zinc and magnesium (all measured in milligrams), before and after the nutritional intervention. A 24-hour recalls will be performed to evaluate amount of folate, vitamin A and D, selenium, lycopene, and flavones (all measured in micrograms), before and after the nutritional intervention.	12 weeks

Collaborators and Investigators

• Sponsor: Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado
• Investigators: Study Chair: Mónica Escamilla Tilch, PhD, CMN "20 de Noviembre"; Principal Investigator: María Fernanda Díaz Yáñez, BSc, CMN "20 de Noviembre"; Principal Investigator: Martha Fernanda Medero López, BSc, CMN "20 de Noviembre"; Study Director: Juan Antonio Pineda Juárez, PhD, CMN "20 de Noviembre"; Study Chair: Martha Orozco Quiyono, MSc, CMN "20 de Noviembre"

Publications and helpful links

General Publications

• Kowalska E, Narod SA, Huzarski T, Zajaczek S, Huzarska J, Gorski B, Lubinski J. Increased rates of chromosome breakage in BRCA1 carriers are normalized by oral selenium supplementation. Cancer Epidemiol Biomarkers Prev. 2005 May;14(5):1302-6. doi: 10.1158/1055-9965.EPI-03-0448.
• Kasai H. Analysis of a form of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutat Res. 1997 Dec;387(3):147-63. doi: 10.1016/s1383-5742(97)00035-5.
• Gopalakrishnan S, Van Emburgh BO, Robertson KD. DNA methylation in development and human disease. Mutat Res. 2008 Dec 1;647(1-2):30-8. doi: 10.1016/j.mrfmmm.2008.08.006. Epub 2008 Aug 20.
• Ferguson LR, Chen H, Collins AR, Connell M, Damia G, Dasgupta S, Malhotra M, Meeker AK, Amedei A, Amin A, Ashraf SS, Aquilano K, Azmi AS, Bhakta D, Bilsland A, Boosani CS, Chen S, Ciriolo MR, Fujii H, Guha G, Halicka D, Helferich WG, Keith WN, Mohammed SI, Niccolai E, Yang X, Honoki K, Parslow VR, Prakash S, Rezazadeh S, Shackelford RE, Sidransky D, Tran PT, Yang ES, Maxwell CA. Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition. Semin Cancer Biol. 2015 Dec;35 Suppl(Suppl):S5-S24. doi: 10.1016/j.semcancer.2015.03.005. Epub 2015 Apr 11.
• Higdon JV, Delage B, Williams DE, Dashwood RH. Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. Pharmacol Res. 2007 Mar;55(3):224-36. doi: 10.1016/j.phrs.2007.01.009. Epub 2007 Jan 25.

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2017
• Primary Completion (Actual): March 22, 2020
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: March 28, 2020
• First Submitted That Met QC Criteria: March 23, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: DNA Damage; Nutrition Therapy; HBOC Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Endocrine System Diseases; Disease; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Breast Diseases; Genetic Diseases, Inborn; Neoplastic Syndromes, Hereditary; Ovarian Neoplasms; Breast Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Syndrome; Hereditary Breast and Ovarian Cancer Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants
• Other Study ID Numbers: ONCONOV001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Will individual participant data be available (including data dictionaries)? No

What data in particular will be shared? Not available

What other documents will be available? Study Protocol, Statistical will be available? Analysis Plan, Informed Consent Form, Clinical Study Report

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No