Elsevier

European Journal of Cancer

Volume 36, Issue 16, October 2000, Pages 2076-2082
European Journal of Cancer

Germ line BRCA1 and BRCA2 gene mutations in Turkish breast cancer patients

https://doi.org/10.1016/S0959-8049(00)00277-XGet rights and content

Abstract

Germ line BRCA1 and/or BRCA2 mutations were screened in 50 Turkish breast and/or ovarian cancer patients composed of hereditary, familial, early onset and male cancer groups. Genomic DNA samples were tested by heteroduplex analysis and DNA sequencing. Two truncating BRCA2 mutations, one novel (6880 insG) and one previously reported (3034 delAAAC), were found in two out of six (33%) hereditary breast and/or ovarian cancer patients. A novel truncating (1200 insA) and a missense (2080A→G) BRCA1 mutation was found in two of 27 (7%) individuals in the early onset group. A total of four (8%) disease-causing mutations in 50 breast cancer patients were identified in BRCA1 and BRCA2 genes. In addition, five BRCA1 sequence variants have been identified in 23 patients. These results indicate that BRCA1 and BRCA2 genes are involved in some, but not all, forms of hereditary predisposition to breast cancer in the Turkish population.

Introduction

Breast cancer is one of the most common malignancies affecting women [1] (http://www.nci.nih.gov/public/factbook98/incidence.htm). Inherited gene mutations may be responsible for 5–10% of breast cancer cases 1, 2, 3. Ovarian cancer is also known to have a familial component [4].

Two genes associated with inherited predisposition to breast and/or ovarian cancer have been identified. These are BRCA1 on chromosome 17q12-21 [1], and BRCA2 on chromosome 13q12-13 [5]. Population genetics studies aimed at determining the relative contributions of these genes in hereditary breast and/or ovarian cancer have shown a wide variation among different populations [6]. For example, in families with three or more cases of female breast and/or ovarian cancer, BRCA1 mutations are as low as 9% in Iceland and as high as 79% in Russia. A similar variation has been documented for BRCA2 mutations as well, which can be exemplified by 8% in Finland and 64% in Iceland. In affected women before the age of 45 years with a first-degree relative, BRCA1 mutations account for 7% of the families [7]. In families with both male and female breast cancer, BRCA2 mutations were documented in 19% of North American, 33% of Hungarian and 90% of Icelandic populations [6]. In isolated male breast cancer cases, a very low frequency of BRCA2 mutations has been reported [8]. In early onset breast and/or ovarian cancer patients not selected for family history, 4–9% have BRCA1, and 2–8% have BRCA2 mutations 6, 7.

Breast cancer is among the most common malignancies in Turkish women [9]. The frequency and the types of germ line mutations involved in Turkish breast/ovarian cancers are not well known. In order to determine the contributions of BRCA1 and BRCA2 mutations to the development of breast and/or ovarian cancer in the Turkish population, we screened preselected regions of these genes in four groups of patients composed of hereditary and familial cancer, as well as early onset and male breast cancer.

Section snippets

Families

We analysed a total of 50 genomic DNA samples isolated from the white blood cells of breast cancer patients. The samples were collected from the Medical Schools of Hacettepe, Istanbul, Ankara Universities, and Ankara Oncology Hospital. Informed consent was obtained from all participants. Each proband was interviewed for pedigree construction including information concerning the family history of breast, ovarian and other cancers. Based on the pedigree analysis, patients were divided into four

Results

Germ line BRCA1 and/or BRCA2 mutations were screened in 50 breast and/or ovarian cancer patients from Turkey. We employed a BRCA1 and BRCA2 mutation screening strategy which is based on the localisation of previously reported mutations in these genes. Selected regions of BRCA1 (exons 2, 5, 11, 13, 20 and 24), and BRCA2 (exon 11) were subjected to heteroduplex analysis, and altered fragments were further analysed by DNA sequencing. According to the BIC database

Discussion

A wide variation in the BRCA1 and BRCA2 mutation spectrum and frequency has been reported for different populations [6]. The results of our Turkish data are summarised in Table 5. In the hereditary breast cancer group, BRCA2 mutations accounted for 33% of cases. This frequency is rather high and similar to the Icelandic population. Interestingly, BRCA1 mutations in our study group appear to be rare — if not exceptional, similar to patients from Iceland, Norway and Japan. However, in a recently

Acknowledgments

We thank Ms Lütfiye Mesci for oligonucleotide synthesis, and Dr Rengül Çetin Atalay for help in secondary structure prediction. This work was supported by grants from Bilkent Holding, TTGV, and TWAS. Hilal Özdag is a recipient of a TÜBITAK-BDP fellowship.

References (15)

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