scholarly journals BRCA Genes and Related Cancers: A Meta-Analysis from Epidemiological Cohort Studies

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 905
Author(s):  
Yen-Chien Lee ◽  
Yen-Ling Lee ◽  
Chung-Yi Li
Keyword(s):  
Cohort Studies ◽  
Brca Mutation ◽  
Meta Analysis ◽  
Brca2 Mutation ◽  
Morbidity Rate ◽  
Cancer Syndrome ◽  
Brca1 And Brca2 ◽  
Brca 1 ◽  
Uterine Cancers ◽  
Epidemiological Cohort

Background and Objectives:BRCA1 and BRCA2 are genes located in different chromosomes that are disproportionately associated with hereditary breast and ovarian cancer syndrome. Their association with other cancers remains to be explored. Materials and Methods: We systematically reviewed cohort studies to explore the association of BRCA 1 and BRCA2 with various cancers except lung cancer. We searched PubMed, Medline (EBSCOhost) and relevant articles published up to 10 May 2021. The odds ratio, standardised morbidity rate and cancer-specific standardised incidence ratio were pooled together as relative risk (RR) estimates. Results: Twelve studies were included for analysis. BRCA mutation increased pancreatic and uterine cancers by around 3–5- and 1.5-fold, respectively. BRCA mutation did not increase brain cancer; colorectal cancer; prostate, bladder and kidney cancer; cervical cancer; or malignant melanoma. BRCA2 increased gastric cancer with RR = 2.15 (1.98–2.33). Conclusion: The meta-analysis results can provide clinicians and relevant families with information regarding increased specific cancer risk in BRCA1 and BRCA2 mutation carriers.

BRCA1 and BRCA2 gene mutations and colorectal cancer risk: Systematic review and meta-analysis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 605-605
Author(s):  
Mok Oh ◽  
Ali McBride ◽  
Seongseok Yun ◽  
Sandipan Bhattacharjee ◽  
Marion Slack ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cohort Studies ◽  
Random Effects ◽  
Brca Mutation ◽  
Meta Analysis ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Brca Mutation Carriers ◽  
Brca1 Brca2 ◽  
Meta Analyses

605 Background: The risks of breast and ovarian cancer associated with BRCA1 and BRCA2 mutations are well established. Investigations of the association of BRCA mutations and the risk of colorectal cancer(CRC) have yielded conflicting results. We performed a systematic review of published and unpublished studies evaluating BRCA and CRC risk, and meta-analyses to quantify overall CRC risk and in subgroups of BRCA mutation carriers. Methods: Eligible studies were retrieved from PubMed/MEDLINE, Embase, Cochrane, Scopus, and ProQuest Dissertation & Theses. Unadjusted odds ratios were used to derive pooled estimates of CRC risk overall (combined BRCA1/BRCA2) and in subgroups defined by mutation type, comparison group, and study design. Both fixed and random effects models were estimated with the latter having priority. We followed the guidelines summarized in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as well as the Meta-analysis of Observational Studies in Epidemiology (MOOSE) statements. Results: A total of 18 studies were included in the systematic review: 7 cohort studies comparing to the general population, 5 case-control studies, 4 cohort studies involving pedigree analysis, and 2 kin-cohort studies. Fourteen studies included in the systematic review were used in the meta-analysis. The overall BRCA1/BRCA2 meta-analysis revealed an increased CRC risk in a fixed-effects (OR = 1.22, 95%CI = 1.01-1.48, p = 0.041, I2= 19.5%) but not in a random-effects model (OR = 1.20, 95%CI = 0.96-1.50, p = 0.111). In subgroup random-effects meta-analyses, BRCA1 was associated with increased CRC risk (OR = 1.48, 95%CI = 1.13-1.94, p = 0.005, I2= 3.7%) but BRCA2 was not. Analyses stratified by study design and comparator found no association between BRCA mutation and CRC risk (all 95%CIs crossing 1, all p > 0.05). Conclusions: Although studies differed in their findings about the association between BRCA mutations and CRC risk, meta-analyses revealed a potential 1.22-fold greater risk of CRC in BRCA mutation carriers. This elevated CRC risk was attributable largely to a 1.48-fold greater risk in BRCA1 mutation but not in BRCA2 carriers, regardless of age.

scholarly journals BRCA1 and BRCA2 Gene Mutations and Lung Cancer Risk: A Meta-Analysis

Medicina ◽  
2020 ◽  
Vol 56 (5) ◽  
pp. 212
Author(s):  
Yen-Chien Lee ◽  
Yang-Cheng Lee ◽  
Chung-Yi Li ◽  
Yen-Ling Lee ◽  
Bae-Ling Chen
Keyword(s):  
Lung Cancer ◽  
Meta Analysis ◽  
Brca2 Mutation ◽  
Gene Mutations ◽  
Brca2 Gene ◽  
Morbidity Rate ◽  
Brca1 And Brca2 ◽  
Increased Risk ◽  
Cancer Types ◽  
Retrospective Study Design

Background and objective: BRCA1 and BRCA2 are associated with many cancer types in addition to hereditary breast and ovarian cancers. However, their relation to lung cancer remains to be explored. Materials and Methods: Observation studies were systematically reviewed to explore the association of BRCA1 or BRCA2 with lung cancer. PubMed, MEDLINE [EBSCOhost], and relevant articles published up to 7 January 2020 were searched. Odd ratio (OR), standardized morbidity rate (SMR), and cancer-specific standardized incidence ratios (SIRs) were pooled together as relative risk (RR) estimates (95% confidence interval [CI], 0.66–1.40). Results: Thirteen studies were included for analysis. Results showed that the RR of BRCA2 is 0.76 (95% CI, 0.48–1.19), the overall RR is 0.96 (95% CI, 0.66–1.40), and that of BRCA1 is 0.66 (95% CI, 0.41–1.05), indicating that it was not associated with lung cancer. Conclusion: With the limitation of the retrospective study design and severe heterogeneity, these results inform clinicians and relevant families that BRCA1 and BRCA2 mutation carriers have no increased risk of lung cancer.

scholarly journals Dramatic response of FOLFIRINOX regimen in a collision pancreatic adenocarcinoma patient with a germline BRCA2 mutation: a case report

2019 ◽  
Vol 49 (11) ◽  
pp. 1049-1054 ◽  
Author(s):  
Hideki Shimmura ◽  
Hidekazu Kuramochi ◽  
Norie Jibiki ◽  
Satoshi Katagiri ◽  
Takayoshi Nishino ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Ductal Carcinoma ◽  
Past History ◽  
Brca Mutation ◽  
Primary Tumour ◽  
Brca2 Mutation ◽  
Breast Tumour ◽  
Metastatic Tumour ◽  
Brca1 And Brca2 ◽  
Platinum Based Chemotherapy

Abstract Germline BRCA1 and BRCA2 mutations are the most common gene mutations in familial pancreatic adenocarcinoma. Several reports have demonstrated the utility of platinum-based chemotherapy for treating cancer patients who harbour a BRCA mutation. Here we discuss a 47-year-old Japanese female with no relevant past history who presented with epigastralgia and fever in September 2016. A computed tomography scan revealed a low-density, low-enhanced tumour 15 mm in diameter in the head of the pancreas. The pathological diagnosis was a ductal pancreatic carcinoma. A 6 mm low-enhanced metastatic tumour was also detected in segment 4 of the liver. Because she had early onset of the disease and a family history—her mother died of pancreatic adenocarcinoma at age 48—we considered a diagnosis of familial pancreatic adenocarcinoma. She received modified FOLFIRINOX. Two months after starting chemotherapy, she was diagnosed with an invasive ductal carcinoma in the right breast. FOLFIRINOX was continued for 8 cycles (4 months); the primary pancreatic adenocarcinoma shrank and the liver metastatic foci disappeared, but the size of the breast tumour increased. Total right breast excision and sentinel lymph node dissection were performed. FOLFIRINOX was continued and after 12 cycles (6 months), both her pancreatic adenocarcinoma and liver metastasis were no longer visible using imaging. Pancreatoduodenectomy was performed and the primary tumour had shrunk to 2.5 mm. Genetic testing revealed a germline BRCA2 mutation. The FOLFIRINOX regimen showed dramatic effects on the collision pancreatic but not on the breast cancer.

Cost effectiveness of in vitro fertilisation and preimplantation genetic testing to prevent transmission of BRCA1/2 mutations

2020 ◽  
Vol 35 (2) ◽  
pp. 434-445 ◽  
Author(s):  
Joseph H Lipton ◽  
Mahdi Zargar ◽  
Ellen Warner ◽  
Ellen E Greenblatt ◽  
Esther Lee ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Cost Effectiveness ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Cost Effective ◽  
In Vitro Fertilisation ◽  
Brca1 And Brca2 ◽  
Preimplantation Genetic Testing ◽  
The Cost

Abstract STUDY QUESTION Is it cost-effective to use in vitro fertilisation and preimplantation genetic testing of monogenic defects (IVT/PGT-M) to prevent transmission of BRCA1/2 mutations to second-generation new births in comparison with naturally conceived births? SUMMARY ANSWER In this cost-effectiveness analysis, we found that IVF/PGT-M is cost-effective for BRCA1 and BRCA2 mutation carriers if using a willingness to pay of $50 000 per quality-adjusted life-year (QALY). WHAT IS KNOWN ALREADY Carriers of a BRCA1 or BRCA2 mutation have a significantly increased risk of several types of cancer throughout their lifetime. The cost of risk reduction, screening and treatment of cancer in this population is high. In addition, there is a 50% chance of passing on this genetic mutation to each child. One option to avoid transmission of an inherited deleterious gene to one’s offspring involves in vitro fertilisation with preimplantation genetic testing. STUDY DESIGN, SIZE, DURATION We implemented a state transition model comparing the healthcare impact of a cohort of healthy children born after IVF/PGT-M, who have a population risk of developing cancer, to a cohort of naturally conceived live-births, half of whom are carriers of the BRCA mutation. Transition probabilities are based on published sources, a lifetime horizon and a perspective of a provincial Ministry of Health in Canada. PARTICIPANTS/MATERIALS, SETTING, METHODS The target population is the second-generation new births who have at least one parent with a known BRCA1 or BRCA2 mutation. MAIN RESULTS AND THE ROLE OF CHANCE At a willingness-to-pay threshold of $50 000 per QALY, IVF/PGT-M is a cost-effective intervention for carriers of either BRCA mutation. For BRCA1, the incremental cost-effectiveness ratio (ICER) for IVF/PGT-M is $14 242/QALY. For BRCA2, the ICER of intervention is $12 893/QALY. Probabilistic sensitivity analysis results show that IVF/PGT-M has a 98.4 and 97.3% chance of being cost-effective for BRCA1 and BRCA2 mutation carriers, respectively, at the $50 000/QALY threshold. LIMITATIONS, REASONS FOR CAUTION Our model did not include the short-term negative effect of IVF/PGT-M on the woman’s quality of life; in addition, our model did not consider any ethical issues related to post-implantation genetic testing. WIDER IMPLICATIONS OF THE FINDINGS In countries in which the healthcare of a large segment of the population is covered by a single payer system such as the government, it would be cost-effective for that payer to cover the cost of IVF/PGT-M for couples in which one member has a BRCA mutation, in order to avoid the future costs and disutility of managing offspring with an inherited BRCA mutation. STUDY FUNDING/COMPETING INTEREST(S) Dr Wong’s research program was supported by the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council (NSERC), the Canadian Liver Foundation and an Ontario Ministry of Research, Innovation and Science Early Researcher Award. All authors declared no conflict of interests.

scholarly journals Polymorphic Repeat Length in the AIB1 Gene and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: A Meta-Analysis of Observational Studies

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e57781
Author(s):  
Aida Bianco ◽  
Barbara Quaresima ◽  
Claudia Pileggi ◽  
Maria Concetta Faniello ◽  
Carlo De Lorenzo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Observational Studies ◽  
Meta Analysis ◽  
Brca2 Mutation ◽  
Repeat Length ◽  
Brca1 And Brca2 ◽  
Mutation Carriers

Moving Toward Personalized Medicine: Treatment-Focused Genetic Testing of Women Newly Diagnosed With Ovarian Cancer

2010 ◽  
Vol 20 (5) ◽  
pp. 704-716 ◽  
Author(s):  
Alison H. Trainer ◽  
Bettina Meiser ◽  
Kaaren Watts ◽  
Gillian Mitchell ◽  
Kathy Tucker ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Mutation Frequency ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Age At Onset ◽  
Prognostic Significance ◽  
Brca1 And Brca2 ◽  
Germline Brca Mutation

Objectives:The presence of a germline BRCA mutation defines a genotype-specific group of women whose invasive ovarian cancer is associated with an increasingly well-defined prognostic and chemosensitivity biological profile. To determine the criteria that may be used to select patients for BRCA treatment-focused genetic testing, we performed a systemic literature search of studies that assessed BRCA1 and BRCA2 mutation frequency in women with ovarian cancer unselected for family history. The results are discussed with regard to the added clinical value gained by identifying a germline BRCA mutation at the time of the ovarian cancer diagnosis.Methods:BRCA-related studies were identified in the CD-ROM databases PubMed (including MEDLINE), PsychINFO, and CINAHL and included in the review if they met the following criteria: they (a) assessed mutation frequency in women with ovarian cancer who were unselected for family history and ethnicity, (b) were published in a peer-review journal, (c) between January 1997 and October 2009, and (d) in the English language.Results:Studies investigating the prevalence of BRCA1 or BRCA2 mutations in ovarian cancer patients unselected for family history or ethnicity have found a pathological BRCA mutation rate of approximately 3% to 17%. Without a significant family history, specific features that may be used to target treatment-focused BRCA testing in the ovarian cancer setting include young age at onset (<50 years), high-grade serous tumor histology, and specific ethnicity associated with known BRCA founder mutations.Conclusions:We believe that given the growing appreciation of the prognostic significance of BRCA mutations and the differential chemosensitivity shown by these tumors, as well as the potential of novel agents such as poly(ADP-ribose) polymerase inhibitors, the identification of a germline BRCA mutation concurrent with a new diagnosis of ovarian cancer will significantly impact on tailoring personalized ovarian management in the future.

Contralateral Breast Cancer in BRCA1 and BRCA2 Mutation Carriers

2004 ◽  
Vol 22 (12) ◽  
pp. 2328-2335 ◽  
Author(s):  
Kelly Metcalfe ◽  
Henry T. Lynch ◽  
Parviz Ghadirian ◽  
Nadine Tung ◽  
Ivo Olivotto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Contralateral Breast Cancer ◽  
Brca Mutation ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Contralateral Breast ◽  
Second Primary ◽  
Brca1 And Brca2 ◽  
Breast Cancer Death ◽  
Actuarial Risk

Purpose To estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers after diagnosis and to determine which factors are predictive of the risk of a second primary breast cancer. Patients and Methods Patients included 491 women with stage I or stage II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up. Results The actuarial risk of contralateral breast cancer was 29.5% at 10 years. Factors that were predictive of a reduced risk were the presence of a BRCA2 mutation (v BRCA1 mutation; hazard ratio [HR], 0.73; 95% CI, 0.47 to 1.15); age 50 years or older at first diagnosis (v ≤ 49 years; HR, 0.63; 95% CI, 0.36 to 1.10); use of tamoxifen (HR, 0.59; 95% CI, 0.35 to 1.01); and history of oophorectomy (HR, 0.44; 95% CI, 0.21 to 0.91). The effect of oophorectomy was particularly strong in women first diagnosed prior to age 49 years (HR, 0.24; 95% CI, 0.07 to 0.77). For women who did not have an oophorectomy or take tamoxifen, the 10-year risk of contralateral cancer was 43.4% for BRCA1 carriers and 34.6% for BRCA2 carriers. Conclusion The risk of contralateral breast cancer in women with a BRCA mutation is approximately 40% at 10 years, and is reduced in women who take tamoxifen or who undergo an oophorectomy.

scholarly journals Meta-Analysis ofBRCA1andBRCA2Penetrance

2007 ◽  
Vol 25 (11) ◽  
pp. 1329-1333 ◽  
Author(s):  
Sining Chen ◽  
Giovanni Parmigiani
Keyword(s):  
Cancer Risk ◽  
Meta Analysis ◽  
Brca2 Mutation ◽  
Estimation Methods ◽  
Ovarian Cancer Risk ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
Study Heterogeneity ◽  
Study Population ◽  
Random Effects Modeling

PurposeGenetic counseling is now routinely offered to individuals at high risk of carrying a BRCA1 or BRCA2 mutation. Risk prediction provided by the counselor requires reliable estimates of the mutation penetrance. Such penetrance has been investigated by studies worldwide. The reported estimates vary. To facilitate clinical management and counseling of the at-risk population, we address this issue through a meta-analysis.MethodsWe conducted a literature search on PubMed and selected studies that had nonoverlapping patient data, contained genotyping information, used statistical methods that account for the ascertainment, and reported risks in a useable format. We subsequently combined the published estimates using the DerSimonian and Laird random effects modeling approach.ResultsTen studies were eligible under the selection criteria. Between-study heterogeneity was observed. Study population, mutation type, design, and estimation methods did not seem to be systematic sources of heterogeneity. Meta-analytic mean cumulative cancer risks for mutation carriers at age 70 years were as follows: breast cancer risk of 57% (95% CI, 47% to 66%) for BRCA1 and 49% (95% CI, 40% to 57%) for BRCA2 mutation carriers; and ovarian cancer risk of 40% (95% CI, 35% to 46%) for BRCA1 and 18% (95% CI, 13% to 23%) for BRCA2 mutation carriers. We also report the prospective risks of developing cancer for currently asymptomatic carriers.ConclusionThis article provides a set of risk estimates for BRCA1 and BRCA2 mutation carriers that can be used by counselors and clinicians who are interested in advising patients based on a comprehensive set of studies rather than one specific study.

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