Impact of Risk Factors and Genetic Polymorphism in Metabolic Enzymes on Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers and Non-Mutation Carriers

摘要

One mutation in each BRCA gene, a BRCA2 founder mutation and a rare BRCAl mutation account for most familial breast cancer in a well defined population. Our previous studies show that the penetrance of the BRCA2 mutation varies greatly, suggesting the involvement of modifying factors, genetic and/or environmental. The study group consists of all women in Iceland who have had breast cancer and are alive at the time of study, their female relatives and age matched controls, estimated 5000 women. Hypotheses tested are that environmental risk factors and genetic variation in metabolic enzymes affect, 1. Penetrance of BRCA mutations 2. Breast cancer risk in the population Hypothesis 1. is studied in women with breast cancer who have a BRCA mutation and mutation carrier relatives without breast cancer. Comparison group are women with breast cancer without BRCA mutations and unaffected mutation negative relatives. Risk factors investigated: Reproductive factors, ionizing radiation, physical exercise, alcohol use, smoking, height and weight. The enzymes investigated affect levels of sex hormones and formation of carcinogenic substances. 2. is studied in 1200 women with breast cancer, representative for breast cancer patients in the population, and 1200 age-matched controls without breast cancer, representative for women without breast cancer.