Breast Carcinogenesis: Alcohol Drinking as a Paradigm

Title: Molecular Epidemiology and Mechanisms for Breast Cancer

Principal Investigator: Jo Freudenheim, PhD

Funding Agency: DOD Breast Cancer Research Program (Georgetown University)

Period: 07/01/03 - 07/31/09

Abstract: Many of the causes of breast cancer are known, but many are not. One established risk factor is alcohol drinking. In fact, it is the best documented other than familial and hormonal risk factors, such as number of pregnancies and age at menopause. The reasons why alcohol drinking causes breast cancer have not been well studied. This is an important issue because many women make lifestyle choices about drinking, and there is data that moderate drinking prevents heart disease. Also, alcohol drinking can adversely interact with hormone replacement therapy to increase breast cancer risk further. It also is important to study alcohol drinking because many of the reasons why it causes breast cancer are the same for other risk factors, such as the diet.

We are studying four ways that alcohol drinking can cause breast cancer. Our hypotheses are that breast cancer risk is increased with drinking because:

1) it affects estrogens in the body and a woman's responses to estrogens;
2) it increases oxidative stress and damage to DNA and proteins;
3) it causes mutations via metabolites of alcohol and;
4) by interacting with dietary folic acid to affect gene regulation and mutations.

Further, we hypothesize that each of these mechanisms are affected by genetic traits, as well as diet. It is expected that some of the mechanisms will play greater roles than others. Definitive conclusions will come from examining the evidence from complementary and corroborative study designs.