Abstract
BackgroundBreast cancer is the world’s most common cancer among women. It is becoming an increasingly urgent problem in low- and middle-income countries (LMICs) where a large fraction of women is diagnosed with advanced-stage disease and have no access to treatment or basic palliative care. About 5-10% of all breast cancers can be attributed to hereditary genetic components and up to 25% of familial cases are due to mutations in BRCA1/2 genes. Since their discovery in 1994 and 1995, as few as 18 mutations have been identified in BRCA genes in the Tunisian population. The aim of this study is to identify additional BRCA mutations, to estimate their contribution to the hereditary breast and ovarian cancers in Tunisia and to investigate the clinicopathological signatures associated with BRCA mutations.MethodsA total of 354 patients diagnosed with breast and ovarian cancers, including 5 male breast cancer cases, have been investigated for BRCA1/2 mutations using traditional and/or next generation sequencing technologies. Clinicopathological signatures associated with BRCA mutations have also been investigated.ResultsIn the current study, 16 distinct mutations were detected: 10 in BRCA1 and 6 in BRCA2, of which 11 are described for the first time in Tunisia including 3 variations that have not been reported previously in public databases namely BRCA1_c.915T>A; BRCA2_c.-227-?_7805+? and BRCA2_c.249delG. Early age at onset, family history of ovarian cancer and high tumor grade were significantly associated with BRCA status. BRCA1 carriers were more likely to be triple negative breast cancer compared to BRCA2 carriers. A relatively high frequency of contralateral breast cancer and ovarian cancer occurrence was observed among BRCA carriers and was more frequent in patients carrying BRCA1 mutations.ConclusionOur study provides new insights into breast and ovarian cancer genetic landscape in the under-represented North African populations. The prevalence assessment of novel and recurrent BRCA1/2 pathogenic mutations will enhance the use of personalized treatment and precise screening strategies by both affected and unaffected North African cancer cases.
Highlights
Breast cancer is the most common malignancy among women worldwide [1]
Probands were selected based on the following selection criteria [1]: Presence of at least 3 related first or second-degree breast cancer cases at any age [2], Young cancer patients aged less than 35 years [3], Presence of at least two cases of breast or ovarian cancer, regardless of age, and at least one case of pancreatic cancer or prostate cancer in a related first- or second-degree patient [4], one case with triple negative breast cancer (TNBC) at an age ≤40 years [5], one breast cancer and one ovarian cancer cases diagnosed at first or second degree relatives at any age
Our results showed that there were no significant differences between BRCA1 and BRCA2 mutated groups regarding the mean age at diagnosis, the family history of personal cancers, of breast cancer and ovarian cancer (Table 5)
Summary
Breast cancer is the most common malignancy among women worldwide [1]. Incidence and mortality rates of breast cancer differ between populations [1]. BRCA1 and BRCA2 are the most prominent breast cancer susceptibility genes that convey high risk of breast and ovarian cancers [4] Since their discovery, a wide range of mutational spectrum have been described for both genes. More than 1800 distinct BRCA1 and 2000 BRCA2 mutations have been reported in the Breast Cancer Information Core (BIC) database These mutations explain around 20-30% of breast cancer genetic component and seem to be associated with different other cancers such as prostate, pancreatic, endometrial and melanoma [5]. About 5-10% of all breast cancers can be attributed to hereditary genetic components and up to 25% of familial cases are due to mutations in BRCA1/2 genes Since their discovery in 1994 and 1995, as few as 18 mutations have been identified in BRCA genes in the Tunisian population. The aim of this study is to identify additional BRCA mutations, to estimate their contribution to the hereditary breast and ovarian cancers in Tunisia and to investigate the clinicopathological signatures associated with BRCA mutations
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