RASSF1A polymorphism A133S is associated with early onset breast cancer in BRCA1/2 mutation carriers.
نویسندگان
چکیده
The tumor suppressor gene RASSF1A regulates cell cycle progression, apoptosis, and microtubule stability and is inactivated by promoter methylation in approximately 50% of breast cancers. It has been shown previously that the polymorphism A133S in RASSF1A reduces its ability to regulate cell cycle progression and this polymorphism is associated with an increased risk of breast cancer. We analyzed the frequency of RASSF1A A133S in 190 Caucasian women without breast cancer and 653 patients with breast cancer including 138 BRCA1 and BRCA2 (BRCA1/2) mutation carriers, 395 non-BRCA1/2 mutations carriers, and 120 untested for BRCA1/2 mutations. Patients with breast cancer had a higher frequency of A133S than the controls [P = 0.017; odds ratios (OR), 1.71; 95% confidence intervals (95% CI), 1.10-2.66]. There is also a higher frequency of A133S in patients with higher familial breast cancer risk (P = 0.029; OR, 1.76; 95% CI, 1.06-2.92) and patients carrying BRCA1/2 mutations (P = 0.037, OR, 1.82; 95% CI, 1.04-3.18). Importantly, we found that the co-occurrence of a BRCA1 or BRCA2 mutation and A133S in RASSF1A was associated with earlier onset of breast cancer compared with those individuals with either a BRCA1/2 mutation or the A133S polymorphism alone (36.0 versus 42.0 years old, P = 0.002). Our data suggest that the presence of the RASSF1A A133S polymorphism is associated with breast cancer pathogenesis in general and modifies breast cancer age of onset in BRCA1/2 mutations carriers. Our results warrant a large-scale study to examine the effect of the A133S polymorphism in the development of breast and other types of cancers.
منابع مشابه
Minor role of BRCA2 mutation (Exon2 and Exon11) in patients with early-onset breast cancer amongst Iranian Azeri-Turkish women
Objective(s): Breast cancer is the most common cancer in women. Every year, one million new cases are reported worldwide, representing 18% of the total number of cancer in women. Hereditary BRCA1 and BRCA2 mutations account for about 60% of inherited breast cancer and are the only known causes of hereditary breast cancer syndrome. The aim of this study was to determine the frequency of BRCA2 (e...
متن کاملمیزان بیان پروتئینBRCA1 در کارسینوم های مهاجم و درجای پستان و ارتباط آن با مارکر سلول های بنیادی سرطان پستان (CD44) و عوامل پیش آگهی تومور
Introduction : Breast cancer is the most common cancer and the second cause of cancer death among women. Despite recent developments in therapeutic tools about 25% of all the involved cases die annually. The clinical, molecular, and pathologic features of breast cancer in BRCA1 mutation carriers suggest that BRCA1 may function as a stem-cell regulator. The purpose of the current study was to ...
متن کاملجهش های ژنتیکی جدید در ژن های اصلی سرطان پستان (BRCA1/BRCA2) در زنان ایرانی مبتلا به سرطان پستان زودرس
Background: Breast cancer is the most common female malignancy and the main cause of death in mid-aged women. Genetic germ line mutations in BRCAI/BRCA2 in Iranian women with breast or ovarian cancer have not been yet reported. Materials and methods: Clinical data, family history and blood samples were obtained from 83 females aged less than 45 years with primary breast cancer in order to su...
متن کاملPrevalence of BRCA1 and BRCA2 mutations in women with breast carcinoma In Situ and referred for genetic testing.
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متن کاملA single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers.
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ورودعنوان ژورنال:
- Cancer research
دوره 68 1 شماره
صفحات -
تاریخ انتشار 2008