scholarly journals Potential impact of family history–based screening guidelines on the detection of early‐onset colorectal cancer

Cancer ◽  
2020 ◽  
Vol 126 (13) ◽  
pp. 3013-3020 ◽  
Author(s):  
Samir Gupta ◽  
Balambal Bharti ◽  
Dennis J. Ahnen ◽  
Daniel D. Buchanan ◽  
Iona C. Cheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Early Onset ◽  
Screening Guidelines ◽  
Potential Impact ◽  
Early Onset Colorectal Cancer

Molecular screening for lynch syndrome in patients with family history or early-onset colorectal cancer

2006 ◽  
Vol 38 ◽  
pp. S20-S21
Author(s):  
V. Stigliano ◽  
L. Sanchez Mete ◽  
M. Diodoro ◽  
M. Mottolese ◽  
V. Casale
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Lynch Syndrome ◽  
Early Onset ◽  
Molecular Screening ◽  
Early Onset Colorectal Cancer

A de novo deletional germline mutation in the MLH1 gene resulting in early onset colorectal cancer in a woman with a negative family history: A case report

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21067-21067
Author(s):  
D. Zakalik ◽  
N. S. Goldstein ◽  
W. L. Ducaine
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Early Onset ◽  
De Novo ◽  
Germline Mutations ◽  
De Novo Mutations ◽  
Mlh1 Gene ◽  
Negative Family History ◽  
Mmr Genes ◽  
Early Onset Colorectal Cancer

21067 Background: Hereditary non-polyposis colorectal cancer (HNPCC) is a genetic disorder that results in an increased risk of early onset colorectal cancer (CRC). HNPCC is caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1 and MSH2, and is transmitted in an autosomal dominant manner. De novo germline mutations in MMR genes are exceedingly rare. We now describe a case of a de novo germline mutation in MLH1 associated with early onset CRC in a young woman with a negative family history. Methods: We present a case of a 31-year-old Caucasian female who presented with abdominal pain. Colonoscopy revealed a moderately differentiated adenocarcinoma with focal mucin production involving the sigmoid colon, with a final staging of T4N0M0. Genetic testing was offered because of her young age at diagnosis, having fulfilled the Bethesda guidelines. Microsatellite instability (MSI) testing using a panel of six microsatellite loci was performed on the tumor sample from the affected patient. Immunohistochemistry (IHC) testing for MLH1 and MSH2 was performed. Following counseling and with informed consent, DNA was isolated and sequenced using bi-directional PCR of the MLH1 gene. All exons of MLH1 and MSH2 were analyzed by standard Southern blot methods. Paternity was established using eight genetic loci. Results: The patient's tumor revealed high MSI and complete absence of MLH1 immunoreactivity. MSH2 IHC staining was normal. A large deletional mutation involving exons 5–12 of MLH1 was identified by Southern blot analysis. The patient's parents and siblings were tested and found to have wild type MLH1. Paternity was confirmed with greater than 99.9% certainty. Conclusions: De novo mutations in MMR genes are a rare cause of HNPCC. We report the first case of a large de novo deletion in the MLH1 gene accounting for early onset CRC. Such de novo mutations, albeit rare, must be considered in patients who present with early onset CRC and a negative family history. These results support the use of the Bethesda guidelines to identify individuals who may carry mutations in the MMR genes. No significant financial relationships to disclose.

Use of Molecular Tumor Characteristics to Prioritize Mismatch Repair Gene Testing in Early-Onset Colorectal Cancer

2005 ◽  
Vol 23 (27) ◽  
pp. 6524-6532 ◽  
Author(s):  
Melissa C. Southey ◽  
Mark A. Jenkins ◽  
Leeanne Mead ◽  
Jonathan Whitty ◽  
Melanie Trivett ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Protein Expression ◽  
Cancer Patients ◽  
Gene Mutation ◽  
Early Onset ◽  
Amsterdam Criteria ◽  
Colorectal Cancer Patients ◽  
Early Onset Colorectal Cancer ◽  
Mmr Proteins

Purpose The relationships between mismatch repair (MMR) protein expression, microsatellite instability (MSI), family history, and germline MMR gene mutation status have not been studied on a population basis. Methods We studied 131 unselected patients with colorectal cancer diagnosed younger than age 45 years. For the 105 available tumors, MLH1, MSH2, MSH6, and PMS2 protein expression using immunohistochemistry (IHC) and MSI were measured. Germline DNA was screened for hMLH1, hMSH2, hMSH6, and hPMS2 mutations for the following patients: all from families fulfilling the Amsterdam Criteria for hereditary nonpolyposis colorectal cancer (HNPCC); all with tumors that were high MSI, low MSI, or that lacked expression of any MMR protein; and a random sample of 23 with MS-stable tumors expressing all MMR proteins. Results Germline mutations were found in 18 patients (nine hMLH1, four hMSH2, four hMSH6, and one hPMS2); all tumors exhibited loss of MMR protein expression, all but one were high MSI or low MSI, and nine were from a family fulfilling Amsterdam Criteria. Sensitivities of IHC testing, MSI (high or low), and Amsterdam Criteria for MMR gene mutation were 100%, 94%, and 50%, respectively. Corresponding positive predictive values were 69%, 50%, and 75%. Conclusions Tumor IHC analysis of four MMR proteins and MSI testing provide a highly sensitive strategy for identifying MMR gene mutation–carrying, early-onset colorectal cancer patients, half of whom would have been missed using Amsterdam Criteria alone. Tumor-based approaches for triaging early-onset colorectal cancer patients for MMR gene mutation testing, irrespective of family history, appear to be an efficient screening strategy for HNPCC.

A positive family history of cancer or lifestyle factors may not explain the high incidence of early-onset colorectal cancer in India

2014 ◽  
Vol 3 (5) ◽  
pp. 409-416
Author(s):  
Ratheesh Raman ◽  
Viswakalyan Kotapalli ◽  
Mohana Vamsy ◽  
Sujit C Patnaik ◽  
Mukta Srinivasulu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Early Onset ◽  
Positive Family History ◽  
Lifestyle Factors ◽  
Family History Of Cancer ◽  
High Incidence ◽  
History Of ◽  
Early Onset Colorectal Cancer ◽  
History Of Cancer

Risk factors for early-onset colorectal cancer in China.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10542-10542
Author(s):  
Zhe Pan ◽  
Junfeng Huang ◽  
Mingkai Huang ◽  
Zhiyuan Yao ◽  
Jiongqiang Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Cohort Study ◽  
Family History ◽  
Early Onset ◽  
Cancer Site ◽  
Family History Of Cancer ◽  
History Of ◽  
Early Onset Colorectal Cancer ◽  
History Of Cancer

10542 Background: The incidence of colorectal cancer among persons aged < 50 years (early-onset colorectal cancer, EOCRC) has increased since the early 1990s. However, the risk factors contributing to this trend remain largely unknown. Methods: We conducted a retrospective study of participants who were aged < 50 years and without a previous cancer history, using the China Kadoorie Biobank cohort study. We analyzed data related to demographics, lifestyle habits, family history, and comorbidities of EOCRC cases with participants without colorectal cancer in this age group (controls). Univariate and multivariate-adjusted cox regression models were used to estimate the associations with risk factors. Results: We identified 225 EOCRC cases and 88842 controls that include the final analyses. Of the 225 EOCRC patients, 105 (46.7%) were colon cancers and 120 (53.3%) were rectum cancers. EOCRC cases were older, have more intake of fish and eggs, have higher BMIs, diabetes, and family history of cancer compared with controls (P < 0.05). After adjustment for potential confounding factors, increasing age (HR 2.18, 95%CI 2.05-2.31), BMI (HR 1.06, 95%CI 1.01-1.11), family history of cancer (HR 1.41, 95%CI 1.00-1.98), and more intake of fish (HR 1.54, 95%CI 1.09-2.19) were significantly associated with a higher risk of EOCRC. In sensitivity analyses stratified by cancer site (colon and rectum), the results remained consistent. Conclusions: Based on the large Chinese cohort study, we found increasing age, higher BMI or obesity, family history of cancer, and more intake of fish were independent risk factors for EOCRC. Further studies are needed to identify factors that cause the increasing incidence of EOCRC in China and other countries, and explore the potential mechanism behind.[Table: see text]

Su1851 Family History and Pathology Features in Early-Onset Colorectal Cancer Cases With a BRAF P.V600e Mutation

2012 ◽  
Vol 142 (5) ◽  
pp. S-519
Author(s):  
Daniel D. Buchanan ◽  
Aung Ko Win ◽  
Rhiannon J. Walters ◽  
Michael D. Walsh ◽  
Mark Clendenning ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Early Onset ◽  
Early Onset Colorectal Cancer
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