scholarly journals Identification of CHEK2 germline mutations in BRCA1/2 and PALB2 negative breast and ovarian cancer patients

2022 ◽  
Author(s):  
Fuat Aksoy ◽  
Havva Tezcan Unlu ◽  
Gulsah Cecener ◽  
Gamze Guney Eskiler ◽  
Unal Egeli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Patients ◽  
Early Onset ◽  
Mutational Analysis ◽  
Turkish Population ◽  
Heteroduplex Analysis ◽  
Chek2 Gene ◽  
Increased Risk ◽  
Wide Range

Introduction: The CHEK2 gene is known to be an important signal transducer involved in DNA repair, apoptosis, or cell cycle arrest in response to DNA damage. The mutations in this gene have been associated with a wide range of cancers, both sporadic and hereditary. Germline CHEK2 mutations are linked to an increased risk of breast cancer. Therefore, the aim of this study was to identify the prevalence of CHEK2 variants in BRCA1/2 and PALB2 negative early-onset patients with breast cancer and/or ovarian cancer in a Turkish population for the first time. Methods: The study included 95 patients with BRCA1/2 and PALB2 negative early-onset breast cancer and/or ovarian cancer and also 60 unaffected women. All the intron/exon boundaries and coding exons of CHEK2 were subjected to mutational analysis by heteroduplex analysis and DNA sequencing. Results: A total of 16 CHEK2 variants were found in breast cancer patients within the Turkish population. CHEK2 c.1100delC mutation studied in the CHEK2 gene most frequently was not detected in our study. The prevalence of variants of uncertain significance in CHEK2 was found to be 7.3% (n= 7) in BRCA1/2 and PALB2 mutation negative Turkish patients with early-onset breast and/or ovarian cancer. Discussion/Conclusion: The present study may shed light on alternative variations that could be significant for understanding the prevalence and clinical suitability of the CHEK2 gene.

scholarly journals GT198 (PSMC3IP) germline variants in early-onset breast cancer patients from hereditary breast and ovarian cancer families

2017 ◽  
Vol 8 (1-2) ◽  
pp. 472-483 ◽  
Author(s):  
Stephanie Schubert ◽  
Tim Ripperger ◽  
Melanie Rood ◽  
Anthony Petkidis ◽  
Winfried Hofmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Patients ◽  
Early Onset ◽  
Breast Cancer Patients ◽  
Early Onset Breast Cancer ◽  
Breast And Ovarian Cancer ◽  
Germline Variants

Gastrointestinal cancer risk in Irish hereditary breast ovarian cancer families.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 413-413
Author(s):  
Darragh S Gogarty ◽  
Tomas Lyons ◽  
Michael P. Farrell ◽  
Naoise Maria Dorman ◽  
Andrew J Green ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Risk ◽  
Lynch Syndrome ◽  
Early Onset ◽  
Carrier Status ◽  
Hereditary Breast Ovarian Cancer ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Age Of Diagnosis

413 Background: Colorectal and breast cancer are linked in certain predisposition syndromes such as Cowden and Peutz-Jegers syndrome. Breast cancer risk also appears increased in certain Lynch syndrome kindreds. Original reports suggested an increased risk of colorectal malignancies in BRCA1/2 mutation carriers. Two large studies in Ashkenazi Jewish populations subsequently contradicted this early evidence, although neither study was powered to address effects if each gene independently, or other modifier effects in certain families. We report the Irish experience of colorectal and gastro-esophageal (GE) cancer in hereditary breast ovarian cancer (HBOC) families. Methods: 97 HBOC families at two tertiary referral centres were reviewed for the presence of early onset GE malignancies. The medical records of individuals with GE cancer were reviewed to determine carrier status. Clinical data including age of diagnosis, stage, treatment and outcome were extracted. Median age of diagnosis and outcome were compared among BRCA1/2 mutation carriers and non-carriers. Results: We identified 30 individuals with GE malignancies in 97 HBOC families (19 with colorectal, 11 with gastric). Two families were excluded as Lynch syndrome was also diagnosed in these families. Definitive carrier status was available on 8 individuals. Additional 7 individuals were obligate carriers. Age at diagnosis ranged from 27-84 years (median=60). Median age of CRC diagnosis among carriers was 54 compared with 61 among non-carriers (p=0.20). Median age of gastric diagnosis among carriers was 66 compared with 53 among non-carriers. Conclusions: Early onset colorectal cancer occurs in certain HBOC families and may be related to mutation status. No genotype-phenotype association was identified in this study. An additional 150 Irish HBOC families are being screened for early onset GI malignancies and updated data will be presented at the meeting.

scholarly journals Spectrum and prevalence of BRCA1/2 germline mutations in Pakistani breast cancer patients: results from a large comprehensive study

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Muhammad Usman Rashid ◽  
Noor Muhammad ◽  
Humaira Naeemi ◽  
Faiz Ali Khan ◽  
Mariam Hassan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Patients ◽  
Male Breast Cancer ◽  
Early Onset ◽  
Germline Mutations ◽  
Male Breast ◽  
Breast Cancer Patients ◽  
Early Onset Breast Cancer ◽  
Pakistani Population

Abstract Background Pathogenic germline mutations in BRCA1 and BRCA2 (BRCA1/2) account for the majority of hereditary breast and/or ovarian cancers worldwide. To refine the spectrum of BRCA1/2 mutations and to accurately estimate the prevalence of mutation in the Pakistani population, we studied 539 breast cancer patients selected for family history and age of diagnosis. Methods Comprehensive screening for BRCA1/2 germline mutations was performed using state-of-the-art technologies. Results A total of 133 deleterious mutations were identified in 539 families (24.7%), comprising 110 in BRCA1 and 23 in BRCA2. The prevalence of BRCA1/2 small-range mutations and large genomic rearrangements was 55.4% (36/65) for families with breast and ovarian cancer, 27.4% (67/244) for families with two or more cases of breast cancer, 18.5% (5/27) for families with male breast cancer, and 12.3% (25/203) for families with a single case of early-onset breast cancer. Nine mutations were specific to the Pakistani population. Eighteen mutations in BRCA1 and three in BRCA2 were recurrent and accounted for 68.2% (75/110) and 34.8% (8/23) of all identified mutations in BRCA1 and BRCA2, respectively. Most of these mutations were exclusive to a specific ethnic group and may result from founder effects. Conclusions Our findings show that BRCA1/2 mutations account for one in four cases of hereditary breast/ovarian cancer, one in five cases of male breast cancer, and one in eight cases of early-onset breast cancer in Pakistan. Our study suggests genetic testing of an extended panel of 21 recurrent BRCA1/2 mutations for appropriately selected patients and their families in Pakistan.

scholarly journals A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

2021 ◽  
Vol 22 (2) ◽  
pp. 889
Author(s):  
Ava Kwong ◽  
Cecilia Y. S. Ho ◽  
Vivian Y. Shin ◽  
Chun Hang Au ◽  
Tsun Leung Chan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Brca1 Gene ◽  
Pathogenic Mutation ◽  
Compound Heterozygous ◽  
Strong Family History ◽  
Breast And Ovarian Cancer ◽  
Pathogenic Mutations ◽  
Increased Risk ◽  
History Of

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.

Fas gene promoter –670 polymorphism in gynecological cancer

2006 ◽  
Vol 16 (Suppl 1) ◽  
pp. 179-182 ◽  
Author(s):  
M. Ueda ◽  
Y. Terai ◽  
K. Kanda ◽  
M. Kanemura ◽  
M. Takehara ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cervical Cancer ◽  
Cancer Patients ◽  
Germ Line ◽  
Gynecological Cancer ◽  
Gene Promoter ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Significant Difference ◽  
Germ Line Polymorphism

Single-nucleotide polymorphism at −670 of Fas gene promoter (A/G) was examined in a total of 354 blood samples from normal healthy women and gynecological cancer patients. They consisted of 95 normal, 83 cervical, 108 endometrial, and 68 ovarian cancer cases. Eighty-three patients with cervical cancer had statistically higher frequency of GG genotype and G allele than 95 controls (P= 0.0353 and 0.0278, respectively). There was no significant difference in the genotype or allele prevalence between control subjects and endometrial or ovarian cancer patients. The Fas −670 GG genotype was associated with an increased risk for the development of cervical cancer (OR = 2.56, 95% CI = 1.08–6.10) compared with the AA genotype. The G allele also increased the risk of cervical cancer (OR = 1.60, 95% CI = 1.05–2.43) compared with the A allele. Germ-line polymorphism of Fas gene promoter −670 may be associated with the risk of cervical cancer in a Japanese population.

scholarly journals An Exploration of Heart Failure Risk in Breast Cancer Patients Receiving Anthracyclines with or without Trastuzumab in Thailand: A Retrospective Study

2021 ◽  
Vol 11 (3) ◽  
pp. 484-493
Author(s):  
Jukapun Yoodee ◽  
Aumkhae Sookprasert ◽  
Phitjira Sanguanboonyaphong ◽  
Suthan Chanthawong ◽  
Manit Seateaw ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Factors Associated ◽  
Palliative Intent ◽  
Increased Risk

Anthracycline-based regimens with or without anti-human epidermal growth factor receptor (HER) 2 agents such as trastuzumab are effective in breast cancer treatment. Nevertheless, heart failure (HF) has become a significant side effect of these regimens. This study aimed to investigate the incidence and factors associated with HF in breast cancer patients treated with anthracyclines with or without trastuzumab. A retrospective cohort study was performed in patients with breast cancer who were treated with anthracyclines with or without trastuzumab between 1 January 2014 and 31 December 2018. The primary outcome was the incidence of HF. The secondary outcome was the risk factors associated with HF by using the univariable and multivariable cox-proportional hazard model. A total of 475 breast cancer patients were enrolled with a median follow-up time of 2.88 years (interquartile range (IQR), 1.59–3.93). The incidence of HF was 3.2%, corresponding to an incidence rate of 11.1 per 1000 person-years. The increased risk of HF was seen in patients receiving a combination of anthracycline and trastuzumab therapy, patients treated with radiotherapy or palliative-intent chemotherapy, and baseline left ventricular ejection fraction <65%, respectively. There were no statistically significant differences in other risk factors for HF, such as age, cardiovascular comorbidities, and cumulative doxorubicin dose. In conclusion, the incidence of HF was consistently high in patients receiving combination anthracyclines trastuzumab regimens. A reduced baseline left ventricular ejection fraction, radiotherapy, and palliative-intent chemotherapy were associated with an increased risk of HF. Intensive cardiac monitoring in breast cancer patients with an increased risk of HF should be advised to prevent undesired cardiac outcomes.

scholarly journals Case series: Breast and ovarian cancer syndrome

2016 ◽  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Brca Mutation ◽  
Family Members ◽  
Case Series ◽  
Second Primary ◽  
Time Interval ◽  
Breast And Ovarian Cancer ◽  
Ovarian Carcinomas ◽  
Increased Risk

Aims and Objectives: To report a series of cases with breast and ovarian carcinomas either in same patient or in a family and identifying the importance of BRCA 1,2 genetic testing in such individuals. Materials and Methods: The medical records of breast and ovarian cancer patients operated over past 3 years at a single institute were reviewed retrospectively and their clinical profile, family history, final pathological reports and follow up data was collected. Results: 8 patients were found to have breast and ovarian malignancies, out of which 3 had synchronous breast and ovarian cancers, 4 had metachronous and 1 patient with ovarian cancer had history of breast cancer in family. Median age of presentation to the hospital was 47 years and median time interval in metachronous disease patients was 5.5 years. Conclusion: About 5% of people who have breast cancer and about 10% of women who have ovarian cancer have HBOC, caused by germline mutation in BRCA1, 2 gene. These individuals have increased risk of developing breast cancer at younger age, TNBC, or developing a second primary in breast or ovary plus an overall risk of breast/ovarian/prostate/pancreatic malignancies in other family members due to inheritable mutation. Identification of BRCA mutation in such individuals can help family members to undergo genetic counseling and follow different screening and prevention guidelines from general population thus reducing the cancer risks.

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