Limited significance of family history for presence of BRCA1 gene mutation in Polish breast and ovarian cancer cases

Izabela Brozek,Jadwiga Rachtan,Anna Kluska,Michalina Dabrowska,Anna Niwinska,Aneta Balabas,Magdalena Piatkowska,Jan Steffen,Janusz Limon,Dorota Nowakowska,Magdalena Ratajska

doi:10.1007/s10689-012-9519-5

Abstract

It is estimated that about 5–10% of ovarian and 2–5% of all breast cancer patients are carriers of a germline BRCA1 or BRCA2 gene mutation. Most families with detected BRCA1 or BRCA2 gene mutation are qualified for molecular testing on the basis of family history of breast or ovarian cancers. The purpose of our study was to establish the frequency of positive family history of cancer in a series of Polish consecutive breast and ovarian cancer patients in two groups, with and without the BRCA1 gene mutations. We analysed the prevalence of four of the most common BRCA1 mutations: 5382insC (c.5266dupC), 300T>G (p.181T>G), 185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5). The patient group consisted of 1,845 consecutive female breast and 363 ovarian cancer cases. 19 out of 37 (51%) of BRCA1-positive ovarian cancer patients and 21 out of 55 (39%) BRCA1-positive breast cancer had negative family history of breast and/or ovarian cancer among first- and second-degree relatives. In ovarian cancer patients, negative family history was more frequent in those with 300T>G BRCA1 gene mutation than in 5382insC carriers. This finding indicates the necessity of searching for 300T>G mutation in families with a single diagnosis of ovarian cancer in family. The high frequency of mutations detected in breast cancer patients lacking obvious family history shows that breast cancer patients should be qualified for genetic testing on the basis of wide clinical and pathological criteria.

Highlights

It is currently accepted that about 5–10% of ovarian cancers and 2–5% of breast cancers have a hereditary background arising in BRCA1/2 genes germline mutation carriers
We observed the difference in frequency of positive family history in BRCA1-positive patient groups depending on the Consecutive, newly-diagnosed female breast cancer cases were collected without regard to age or family history of breast and ovarian cancer in two provinces, Malopolska and Mazowsze, between 2003 and 2005
Many centres undertook the screening programme to estimate the prevalence of BRCA1 mutations in breast cancer cases unselected for age and family history of cancer

Summary

Introduction

It is currently accepted that about 5–10% of ovarian cancers and 2–5% of breast cancers have a hereditary background arising in BRCA1/2 genes germline mutation carriers. Because of high costs and cumbersome procedure the mutation testing is offered to patients in whom family history indicates high probability of finding the mutation. Some families with detected mutation have negative family history or limited family structure [1,2,3,4]. The purpose of our study was to establish the frequency and spectrum of BRCA1 gene mutations in Polish consecutive breast and ovarian cancer patients in two groups: with positive and negative family history of BRCA1-related cancers. Our choice of the four BRCA1 mutations: 5382insC (c.5266dupC), 300T[G (p.181T[G), 185delAG (c.68_69delAG), and 3819del

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