NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 3.2017

Gupta, Samir; Provenzale, Dawn; Regenbogen, Scott E.; Hampel, Heather; Slavin, Thomas P.; Hall, Michael J.; Llor, Xavier; Chung, Daniel C.; Ahnen, Dennis J.; Bray, Travis; Cooper, Gregory S.; Early, Dayna S.; Ford, James M.; Giardiello, Francis M.; Grady, William M.; Halverson, Amy L.; Hamilton, Stanley R.; Klapman, Jason; Larson, David W.; Lazenby, Audrey J.; Lynch, Patrick M.; Markowitz, Arnold J.; Mayer, Robert J.; Ness, Reid M.; Samadder, N. Jewel; Shike, Moshe; Sugandha, Shajanpeter; Weiss, Jennifer M.; Dwyer, Mary A.; Ogba, Ndiya

doi:10.6004/jnccn.2017.0176

Cited by 147 publications

(181 citation statements)

References 49 publications

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“…Thus, we concluded that genetic screening in this populations is essential. 14 In this study, pathogenic mutations were identified in 135 patients most of them in the BRCA1/2 gene.The mutation carrier rate was higher than the unselected BC patients (19.5% vs 5.3%). 15 Mutations found in the BRCA1 gene (14.6%) in this cohort were almost three times higher compared to BRCA2 (5%).…”

Section: Disscussionmentioning

confidence: 91%

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Germline mutation landscape of Chinese patients with familial breast/ovarian cancer in a panel of 22 susceptibility genes

Wang

Shi

et al. 2019

Cancer Medicine

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Genetic testing for germline mutations in BRCA1/2 of patients with breast cancer (BC) is part of routine patient care. However, BRCA1/2 mutations account only for a fraction of familial BC. A custom panel of 22 gene sequencing was performed on each patient. Among the 481 female patients, 135 patients were detected to carry pathogenic (P)/likely pathogenic (LP) mutations (28.1%), which corresponded to 12 different cancer predisposition genes [14.6% (70/481) on BRCA1 gene, 5.0% (24/481) on BRCA2 gene, 8.5% (41/481) on non‐ BRCA1/2 genes]. Moreover, 24.7% (119/481) of patients had mutation of unknown significance (VUS) in these genes. The most common (8/481) pathogenic mutation is BRCA1 c.5470_5477del, while BRIP1 2392 C > T of patients was detected. All the mutations detected were mainly seen in the homologous recombinant repair pathway. Compared to BRCA2 mutation, BRCA1 mutation is higher in younger female patients ( P < 0.01). Some pathogenic mutations were detected in the patients’ familiy members without the past history of tumor and 92 novel mutations were detected (31 on BRCA including 2 P, 16 LP, 13 VUS; 61 on non‐ BRCA1/2 including 9 LP, 52 VUS). The detection rate of BRCA1/2 mutations was higher in patients with three or more cancer family members than those with one or two. However, the difference was not statistically different. The results suggest that multigene panel testing can increase mutation detection rate for high‐risk BC patients. Detailed family history can help to categorize new mutations.

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Section: Disscussionmentioning

confidence: 91%

“…Of note, BARD1 and BRIP1 pathogenic mutations were not detected in this study . Other studies showed that BARD1 mutation might be rare and responsible for a few familial BC patients . It has been reported that BRIP1 had a higher penetrance for OC .…”

Section: Disscussionmentioning

confidence: 99%

Germline mutation landscape of Chinese patients with familial breast/ovarian cancer in a panel of 22 susceptibility genes

Wang

Shi

et al. 2019

Cancer Medicine

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“…Similarly, in our small cohort, one APC I1307K moderate risk variant was identified. NCCN currently recommends colonoscopy screening every 5 years beginning at age 40 for unaffected carriers of this variant (Gupta et al 2017). However, it is important to remember that management guidelines for moderate risk genes are (Ferrone et al 2009) largely based on expert opinion rather than evidence-based and more studies with longer follow-up intervals are needed.This study serves to characterize the genetic testing findings from a high-risk cohort of urban AJ individuals.…”

Section: Discussionmentioning

confidence: 99%

Cancer Susceptibility Genetic Testing in a High‐Risk Cohort of Urban Ashkenazi Jewish Individuals

Nielsen

Simone

Olopade

2018

Journal of Genetic Counseling

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Prior to 2013, genetic testing for Ashkenazi Jewish (AJ) individuals primarily consisted of the three-site BRCA1/BRCA2 AJ panel, full sequencing of BRCA1/2, or the Lynch syndrome mismatch repair genes. Multigene panel testing became more widely available in 2013, but limited data are available regarding the impact of multigene panel testing for AJ individuals. Here, we report the frequency of cancer susceptibility gene mutations in a cohort of 427 AJ individuals seen in the Cancer Risk Clinic at The University of Chicago. We found that 29% of affected and 37% of unaffected individuals carried a pathogenic mutation (32% of overall cohort), primarily known familial mutations in BRCA1/2. A minority of mutations were identified in non-BRCA1/2 genes and consisted mainly of AJ founder mutations in CHEK2, APC, and the mismatch repair genes. A panel of AJ founder mutations would have identified the majority (94%) of mutations in clinically actionable genes in both affected and unaffected patients. Based on recent cost-effectiveness studies, offering all AJ individuals a founder mutation panel may be a cost-effective cancer prevention strategy.

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“…None of the patients with CRC had received preoperative radiotherapy or chemotherapy prior to surgery. Following surgery, all patients received standard treatments according to the National Comprehensive Cancer Network guidelines (22). The present study was approved by the Ethics Committee of the Affiliated Hospital of Nantong University.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of GRK6 associates with the progression and prognosis of colorectal carcinoma

Tao

Gao

et al. 2018

Oncol Lett

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Abstract. There are a limited number of studies reporting on the expression of G protein-coupled receptor kinase 6 (GRK6) in colorectal carcinoma (CRC). The aim of the present study was to investigate and examine the clinical value of GRK6 expression in human CRC. The expression of the GRK6 protein was determined in CRC tissues (n=83) and in normal colorectal tissues (n=19) by immunohistochemical (IHC) analysis. In addition, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was conducted to investigate GRK6 mRNA levels in matched pairs of cancerous and non-cancerous fresh frozen tissues from 19 patients with CRC. Furthermore, GRK6 protein levels were evaluated in matched pairs of cancerous and non-cancerous fresh frozen tissues from 19 other patients with CRC by western blot analysis. The expression of GRK6 was significantly upregulated in patients with CRC as indicated by IHC analysis (P=0.028). The results of RT-qPCR and western blotting confirmed that GRK6 mRNA and protein levels were upregulated in CRC tissues compared with matched adjacent non-cancerous tissues (P<0.05). Additionally, GRK6 protein expression was significantly associated with histological differentiation (P=0.001), lymph node invasion (P=0.45), venous invasion (P=0.009), depth of invasion (P=0.026), distant metastasis (P<0.0001) and TNM stages (P=0.020). Survival analysis using the Kaplan-Meier method indicated that patients with high GRK6 expression levels exhibited lower overall survival rates compared with patients with low GRK6 expression. Multivariate analysis using the Cox proportional hazards model indicated that the expression levels of GRK6 (P=0.003) were independent prognostic factors for overall survival in patients. The overexpression of GRK6 in patients with CRC may serve as an independent predictor of patient outcome.

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NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 3.2017

Cited by 147 publications

References 49 publications

Germline mutation landscape of Chinese patients with familial breast/ovarian cancer in a panel of 22 susceptibility genes

Germline mutation landscape of Chinese patients with familial breast/ovarian cancer in a panel of 22 susceptibility genes

Cancer Susceptibility Genetic Testing in a High‐Risk Cohort of Urban Ashkenazi Jewish Individuals

Overexpression of GRK6 associates with the progression and prognosis of colorectal carcinoma

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