scholarly journals DNA repair gene ERCC2 polymorphisms and associations with breast and ovarian cancer risk

2008 ◽  
Vol 7 (1) ◽  
pp. 36 ◽  
Author(s):  
Dominique Bernard-Gallon ◽  
Rémy Bosviel ◽  
Laetitia Delort ◽  
Luc Fontana ◽  
Alain Chamoux ◽  
...  
Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 353
Author(s):  
Jordi Minguillón ◽  
María José Ramírez ◽  
Llorenç Rovirosa ◽  
Pilar Bustamante-Madrid ◽  
Cristina Camps-Fajol ◽  
...  

BRCA2 is essential for homologous recombination DNA repair. BRCA2 mutations lead to genome instability and increased risk of breast and ovarian cancer. Similarly, mutations in BRCA2-interacting proteins are also known to modulate sensitivity to DNA damage agents and are established cancer risk factors. Here we identify the tumor suppressor CDK5RAP3 as a novel BRCA2 helical domain-interacting protein. CDK5RAP3 depletion induced DNA damage resistance, homologous recombination and single-strand annealing upregulation, and reduced spontaneous and DNA damage-induced genomic instability, suggesting that CDK5RAP3 negatively regulates double-strand break repair in the S-phase. Consistent with this cellular phenotype, analysis of transcriptomic data revealed an association between low CDK5RAP3 tumor expression and poor survival of breast cancer patients. Finally, we identified common genetic variations in the CDK5RAP3 locus as potentially associated with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Our results uncover CDK5RAP3 as a critical player in DNA repair and breast cancer outcomes.


2018 ◽  
Vol 10 (2) ◽  
pp. 337-346 ◽  
Author(s):  
Mary Kathleen Ladd ◽  
Beth N Peshkin ◽  
Leigha Senter ◽  
Shari Baldinger ◽  
Claudine Isaacs ◽  
...  

Abstract Risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO) are increasingly used to reduce breast and ovarian cancer risk following BRCA1/BRCA2 testing. However, little is known about how genetic counseling influences decisions about these surgeries. Although previous studies have examined intentions prior to counseling, few have examined RRM and RRSO intentions in the critical window between genetic counseling and test result disclosure. Previous research has indicated that intentions at this time point predict subsequent uptake of surgery, suggesting that much decision-making has taken place prior to result disclosure. This period may be a critical time to better understand the drivers of prophylactic surgery intentions. The aim of this study was to examine predictors of RRM and RRSO intentions. We hypothesized that variables from the Health Belief Model would predict intentions, and we also examined the role of affective factors. Participants were 187 women, age 21–75, who received genetic counseling for hereditary breast and ovarian cancer. We utilized multiple logistic regression to identify independent predictors of intentions. 49.2% and 61.3% of participants reported intentions for RRM and RRSO, respectively. Variables associated with RRM intentions include: newly diagnosed with breast cancer (OR = 3.63, 95% CI = 1.20–11.04), perceived breast cancer risk (OR = 1.46, 95% CI = 1.17–1.81), perceived pros (OR = 1.79, 95% CI = 1.38–2.32) and cons of RRM (OR = 0.81, 95% CI = 0.65–0.996), and decision conflict (OR = 0.80, 95% CI = 0.66–0.98). Variables associated with RRSO intentions include: proband status (OR = 0.28, 95% CI = 0.09–0.89), perceived pros (OR = 1.35, 95% CI = 1.11–1.63) and cons of RRSO (OR = 0.72, 95% CI = 0.59–0.89), and ambiguity aversion (OR = 0.79, 95% CI = 0.65–0.95). These data provide support for the role of genetic counseling in fostering informed decisions about risk management, and suggest that the role of uncertainty should be explored further.


2013 ◽  
Vol 4 ◽  
pp. 290-295 ◽  
Author(s):  
Beata Smolarz ◽  
Marianna Makowska ◽  
Dariusz Samulak ◽  
Magdalena M. Michalska ◽  
Ewa Mojs ◽  
...  

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hamideh Salimzadeh ◽  
Elinor Bexe Lindskog ◽  
Bengt Gustavsson ◽  
Yvonne Wettergren ◽  
David Ljungman

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