Nutritional Intervention and DNA Damage of Patients With HBOC

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
DNA Damage, HBOC Syndrome, Nutrition Therapy

Intervention / Treatment
-----------------
* Combination Product: Antioxidant therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
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).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Antioxidant therapy<br>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<br>* Antioxidant therapy based in the following dietary components: Zinc, Selenium, Magnesium, carotenoids, indole-3-carbinol, curcumin, epigalactocatechin, caffeine, resveratrol, lycopene, genistein, phytoestrogens<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HBOC Syndrome, DNA Damage, Nutrition Therapy