China
Africa
Explore chapters and articles related to this topic
Introduction to Cancer, Conventional Therapies, and Bionano-Based Advanced Anticancer Strategies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
The breast and ovarian cancer risks are increased in patients who carry a BRCA1 mutation, while BRCA2 carriers have an increased risk of prostate, pancreas, and skin cancers [42]. The identification of genetic predisposition to cancer permits screening processes to recognize patients who are at risk of developing certain types of cancer. This will subsequently help them modify potential cancer risk increasing behaviors [43]. Physicians recommend breast surveillance for BRCA heterozygotes, including self-examination, physician examination, and mammography [44].
The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
BRCA1 and BRCA2 are examples of genes that increase the risk of developing breast and ovarian cancer in women, and male breast cancer and prostate cancer in men. BRCA1 provides the instructions needed by a cell to produce tumor suppressor proteins necessary to prevent uncontrollable cell growth and division, thus preventing tumor establishment, growth, and spread. Women carrying the faulty BRCA1 gene have a 60–90% lifetime risk of breast cancer and a 40–60% risk of ovarian cancer (i.e., for every 100 women, 60–90 will develop breast cancer in their lifetime and 40–60 will develop ovarian cancer). There are also population differences; although faulty BRCA genes affect around 1 in every 400 people in most populations, those of Ashkenazi Jewish descent are at much higher risk with as many as 1 in 40 carrying a faulty gene. Recent research has identified over 100 new gene variants associated with an increased risk of breast, prostate, and ovarian cancer. Individually, these new gene variants may only slightly increase the risk of cancer, but the presence of a combination of them could mean a high risk overall.
Practice exam 4: Answers
Published in Euan Kevelighan, Jeremy Gasson, Makiya Ashraf, Get Through MRCOG Part 2: Short Answer Questions, 2020
Euan Kevelighan, Jeremy Gasson, Makiya Ashraf
Identification of cancer susceptibility in a family by genetic counselling and then identification of a gene defect such as BRCA1 or BRCA2 may allow identification of cancer at an early stage or allow prophylactic surgery to be undertaken prior to cancer developing (2).
Breast cancer genetics and risk assessment: an overview for the clinician
Published in Climacteric, 2023
Approximately 5–10% of breast cancer in developed countries is associated with BRCA1 and BRCA2 [11–13], the most common single hereditary gene mutations associated with breast cancer. BRCA1 and BRCA2 are very highly penetrant genes associated with a lifetime risk of developing breast cancer approaching 80%. Approximately 5–15% of women who are negative for BRCA1 and BRCA2 will be found to carry one of the other highly penetrant genes or moderately penetrant genes associated with HBC [13–15] Highly penetrant genes associated with a lifetime risk of breast cancer of >30% include TP53, PTEN, CDH1, STK11 and PALB2. Moderately penetrant genes associated with a 17–30% lifetime risk include CHEK2, ATM, BARD1, BRIP1, NBN, NF1, RAD51D and MSH6 [16]. Breast cancer risk and recommendations for screening and risk reduction vary by gene. In general, screening breast magnetic resonance imaging is recommended for women at >20% lifetime risk, which includes women with mutations in highly penetrant genes and the majority (but not all) of moderately penetrant genes. Consideration of chemoprevention is recommended for women with mutations in high and moderately penetrant genes [13].
The expression and mutation of BRCA1/2 genes in ovarian cancer: a global systematic study
Published in Expert Review of Molecular Diagnostics, 2023
Dinh-Toi Chu, Mai Vu Ngoc Suong, Hue Vu Thi, Thuy-Duong Vu, Manh-Hung Nguyen, Vijai Singh
Among genes linked to ovarian cancer, Breast Cancer 1 (BRCA1) gene and Breast Cancer 2 (BRCA2) gene are two of the most prominent. The population frequencies for BRCA1 and BRCA2 mutations were estimated 0.024% and 0.041%, respectively [12]. Even though the probability of finding any cases with mutation in both BRCA genes is significantly low (from 1/700,000 to 1/250,000), it is possible to find a presence of double heterozygosity in BRCA genes [13]. BRCA1 and BRCA2 genes are located on chromosomes 17 and 13, respectively [14]. BRCA1/2 proteins relate to the homologous recombination (HR) pathway and non-homologous end-joining, which lead to the repair of double-strand breaks (DSBs) on DNA [14,15]. As a result, mutations in BRCA1 and BRCA2 genes cause impaired HR, which is not feasible to repair damaged chromosomes and unrepairable DSBs and forms ovarian tumors [14,16]. In fact, 65–85% of genetic abnormalities are related to ovarian carcinomas, which are germline mutations in BRCA1/2 genes [7]. The lifetime risk of developing ovarian tumors due to BRCA1 mutations and BRCA2 mutations in women are 15–45% and 10–40%, respectively, [17].
Poly (ADP-ribose) polymerase inhibitors (PARPi) for advanced malignancies with multiple DNA-repair genetic aberrations
Published in Expert Review of Anticancer Therapy, 2022
Jian Hu, Peihe Liang, Dachun Jin, Runze Fan, Xiaodu Xie, Chuan Liu, Qing Jiang, Liang Gao
In a phase 2 proof-of-concept trial, Tutt et al. reported a novel targeted treatment strategy in patients with loss-of-function mutations in BRCA1 or BRCA2 [26]. This trial observed one patient with both BRCA1 and BRCA2 mutations in the cohort of olaparib 100 mg twice daily, but the response in terms of survival was not reported separately. In addition, in a randomized, open-label, phase 3 trial, Robson et al. explored olaparib monotherapy compared with standard therapy (capecitabine, eribulin mesylate, or vinorelbine) for patients with a germline BRCA mutation [27]. This trial reported 4 (4/302) patients with both BRCA1 and BRCA2 mutations. However, data related to the response to PARPi were not reported or compared with those from patients with a single mutation.