Genetic studies in familial breast cancer

Sammanfattning: This study focuses on familial breast cancer, where some alteration is supposed to be inherited and predispose the individuals to breast cancer. Even when the majority of breast cancer cases are sporadic, a familial breast cancer study might light on over certain genes involved in the ethiology of the disease. A cohort of 236 families from the Stockholm region is involved in this thesis. The families represented 129 families with hereditary breast or breast-ovarian cancer, 80 families with two close relatives with breast cancer and 27 families with at least 1 case of breast cancer and two or more cases with other types of cancer. Fifty-two of the 236 families were selected from a population of all existing breast cancer patients in Stockholm in a study done 1988-89. The remaining families were recruited through the Cancer Family Clinic at the Karolinska Hospital during 1990-1995. Loss of heterozygosity (LOH) study on chromosome 17q in tumors from breast ovarian cancer families showed few losses in the BRCA1 region. Three different regions of LOH could be distinguished on 17q in familial tumors. No strong correlation was found with lymph node metastases. Mutation screening of TP53 gene in 109 patients revealed no germline mutations, and few somatic mutations in 51 tumors. Mutation screening of the BRCA1 gene resulted in a lower frequency of BRCA1 mutations than expected (33% of breast-ovarian cancer families and less than 1% of the site specific breast cancer families). The alteration in codon 160 of the estrogen receptor gene (ESR) which has been reported in British and Norwegian breast cancer families is not present in this cohort of families. The 999del5 mutation described in the BRCA2 gene, in the Icelandic population could not be found in these families either. Other genes besides BRCA1, BRCA2 and TP53 are likely to be segregating in breast cancer families in the Stockholm region. ISBN 91-628-2495-3 Stockholm 1997