Young age and a positive family history of colorectal cancer are complementary selection criteria for the identification of Lynch syndrome

Background and Aims: Colorectal cancer (CRC) is the third most frequent form of cancer worldwide, and approximately one third of cases have a positive family history of CRC or associated cancers. Colonoscopy is one of the most effective methods of screening for CRC. Uptake of colonoscopy is suboptimal, and many countries lack a national screening programme. Our study aims at exploring and ranking several factual and psychological variables according to their accuracy in discriminating between screeners and non-screeners for CRC in a convenience sample of people over 50 years of age. Methods: The study included 103 individuals aged over 50 years, recruited from day centres for the elderly. We explored socio-demographic variables, frequency of colonoscopy, previous recommendations for screening, health literacy and family history of cancer. Receiver operating characteristic (ROC) analysis was used to establish the discriminative value for each variable between the positive and negative decision for colonoscopy screening. Areas under the curve (AUC) and their equivalent Cohen‘s d values were calculated. Results: Almost a quarter (25.75%) of participants reported previous colonoscopy screening. ROC curve analysis shows that colonoscopy uptake is best discriminated by perceived benefits of screening (AUC=0.71, d=0.78, p<0.001), previous recommendations for screening (AUC=0.68, d=0.69, p<0.001) and previous recommendations for preventive measures (AUC=0.67, d=0.64, p<0.001). Conclusions: Recommendations from healthcare professionals lead to improved colonoscopy uptake when emphasising the benefits of screening. Results can further inform psychosocial interventions by bringing empirical evidence to emphasize screening benefits and explicit recommendations for individuals at risk for CRC cancer.

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Screening of Patients with a Positive Family History of Colorectal Cancer

Gastrointestinal Endoscopy Clinics of North America ◽

10.1016/s1052-5157(18)30323-4 ◽

1997 ◽

Vol 7 (1) ◽

pp. 65-79 ◽

Cited By ~ 23

Author(s):

Randall W. Burt

Keyword(s):

Colorectal Cancer ◽

Family History ◽

Positive Family History ◽

History Of

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Positive family history of colorectal cancer in a general practice setting [FRIDA.Frankfurt]: study protocol of a of a cross-sectional study

BMC Cancer ◽

10.1186/s12885-015-1600-7 ◽

2015 ◽

Vol 15 (1) ◽

Cited By ~ 2

Author(s):

Andrea Siebenhofer ◽

Jasper Plath ◽

Maja Taubenroth ◽

Susanne Singer ◽

Marlene Hechtner ◽

...

Keyword(s):

Colorectal Cancer ◽

General Practice ◽

Family History ◽

Study Protocol ◽

Positive Family History ◽

Cross Sectional Study ◽

Practice Setting ◽

Sectional Study ◽

Cross Sectional ◽

History Of

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An alternative approach to identify women at risk for colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1513 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1513-1513

Author(s):

Amanda S. Bruegl ◽

Bojana Djordjevic ◽

Shannon Neville Westin ◽

Pamela T. Soliman ◽

Amanda C. Brandt ◽

...

Keyword(s):

Colorectal Cancer ◽

Family History ◽

Mismatch Repair ◽

Dna Mismatch Repair ◽

Gynecologic Oncology ◽

Positive Family History ◽

Dna Mismatch ◽

Increased Risk ◽

History Of ◽

Mlh1 Methylation

1513 Background: Hereditary colorectal cancer (CRC) is preventable; however, identification of individuals at sufficiently high risk to warrant heightened surveillance is difficult. Lynch Syndrome (LS) is an inherited cancer syndrome due to germline mutation in a DNA mismatch repair gene. For women with LS, the lifetime risk of endometrial cancer (EC) is 64% and CRC is 54%. Fifty percent of women with LS will present with EC or ovarian cancer prior to CRC. Therefore, women with LS associated EC represent an ideal group for CRC prevention. The optimal method to identify women with LS associated EC is not known. The purpose of this study was to determine the utility of Amsterdam II and Society of Gynecologic Oncology (SGO) Criteria (modified Bethesda criteria that use EC as the sentinel cancer) in identifying women with LS associated EC. Our ultimate goal is to identify women at increased risk of CRC. Methods: Immunohistochemistry (IHC) for DNA mismatch repair proteins and MLH1 methylation analyses were used to identify LS associated EC among 388 women. EC was designated as LS if there was loss of mismatch repair protein expression. Absence of MLH1 methylation was required to confirm LS in tumors with MLH1 protein loss. Results: Fifty-nine (15.2%) of the EC patients tested had LS. These patients are summarized in the table. Conclusions: Clinical criteria to detect LS identify 17/59 (29%) - 44/59 (74%) of women who present with EC first. EC with MSH2 loss is most likely to occur in younger women and women with positive family history of EC and CRC, features classically associated with LS. In general, the MSH6 mutation is associated with older age at diagnosis and fewer familial CRCs, however, we found a large number of MLH1 (50%) and PMS2 (86%) cases diagnosed at greater than 50 years with no family history of CRC. Our data suggest that classic clinical screening criteria are inadequate to detect patients with LS who present with EC, potentially missing up to 25% of these patients. [Table: see text]

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Aberrant crypt foci in patients with a positive family history of sporadic colorectal cancer

Cancer Letters ◽

10.1016/j.canlet.2006.08.003 ◽

2007 ◽

Vol 248 (2) ◽

pp. 262-268 ◽

Cited By ~ 27

Author(s):

Richard G. Stevens ◽

Helen Swede ◽

Christopher D. Heinen ◽

Melissa Jablonski ◽

Michael Grupka ◽

...

Keyword(s):

Colorectal Cancer ◽

Family History ◽

Positive Family History ◽

Aberrant Crypt Foci ◽

Sporadic Colorectal Cancer ◽

History Of

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Rectal Cancer Diagnosed after Cesarean Section in Which High Microsatellite Instability Indicated the Presence of Lynch Syndrome

Case Reports in Obstetrics and Gynecology ◽

10.1155/2015/479753 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5

Author(s):

Tomohiro Okuda ◽

Hiroshi Ishii ◽

Sadao Yamashita ◽

Sakura Ijichi ◽

Seiki Matsuo ◽

...

Keyword(s):

Colorectal Cancer ◽

Rectal Cancer ◽

Family History ◽

Cesarean Section ◽

Lynch Syndrome ◽

Microsatellite Instability ◽

Birth Canal ◽

Emergency Cesarean ◽

History Of ◽

Revised Bethesda Guidelines

We report a case of rectal cancer with microsatellite instability (MSI) that probably resulted from Lynch syndrome and that was diagnosed after Cesarean section. The patient was a 28-year-old woman (gravid 1, para 1) without a significant medical history. At 35 gestational weeks, vaginal ultrasonography revealed a 5 cm tumor behind the uterine cervix, which was diagnosed as a uterine myoma. The tumor gradually increased in size and blocked the birth canal, resulting in the patient undergoing an emergency Cesarean section. Postoperatively, the tumor was diagnosed as rectal cancer with MSI. After concurrent chemoradiation therapy, a lower anterior resection was performed. The patient’s family history revealed she met the criteria of the revised Bethesda guidelines for testing the colorectal tumor for MSI. Testing revealed that the tumor did indeed show high MSI and, combined with the family history, suggested this could be a case of Lynch syndrome. Our findings emphasize the importance of considering the possibility of Lynch syndrome in pregnant women with colorectal cancer, particularly those with a family history of this condition. We suggest that the presence of Lynch syndrome should also be considered for any young woman with endometrial, ovarian, or colorectal cancer.

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A different background of arrhythmia in siblings with a positive family history of sudden death at young age

Annals of Noninvasive Electrocardiology ◽

10.1111/anec.12707 ◽

2019 ◽

Vol 25 (4) ◽

Cited By ~ 1

Author(s):

Małgorzata Stępień‐Wojno ◽

Maria Franaszczyk ◽

Robert Bodalski ◽

Mateusz Śpiewak ◽

Rafał S. Baranowski ◽

...

Keyword(s):

Family History ◽

Sudden Death ◽

Positive Family History ◽

Young Age ◽

History Of

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Prevalence and spectrum of MLH1, MSH2, and MSH6 pathogenic germline variants in Pakistani colorectal cancer patients

Hereditary Cancer in Clinical Practice ◽

10.1186/s13053-019-0128-2 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 1

Author(s):

Muhammad Usman Rashid ◽

Humaira Naeemi ◽

Noor Muhammad ◽

Asif Loya ◽

Jan Lubiński ◽

...

Keyword(s):

Colorectal Cancer ◽

Family History ◽

Lynch Syndrome ◽

Research Centre ◽

Germline Variants ◽

Pathogenic Variants ◽

History Of ◽

Group 2 ◽

Colorectal Cancer Patients ◽

Group 1

Abstract Background Pathogenic germline variants in MLH1, MSH2 and MSH6 genes account for the majority of Lynch syndrome (LS). In this first report from Pakistan, we investigated the prevalence of pathogenic MLH1/MSH2/MSH6 variants in colorectal cancer (CRC) patients. Methods Consecutive cases (n = 212) were recruited at the Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC), between November 2007 to March 2011. Patients with a family history of > 3 or 2 HNPCC-associated cancers were classified as HNPCC (n = 9) or suspected-HNPCC (n = 20), respectively (group 1; n = 29). Cases with no family history were designated as non-HNPCC (group 2; n = 183). MLH1/MSH2/MSH6 genes were comprehensively screened in group 1. Pathogenic/likely pathogenic variants identified in group 1 were subsequently evaluated in group 2. Results Eight distinct pathogenic/likely pathogenic MLH1/MSH2 variants were found in group 1 (10/29; 34.5%), belonging to HNPCC (5/9; 55.6%) and suspected-HNPCC (5/20; 25%) families and in group 2 (2/183; 1.1%) belonging to non-HNPCC. Overall, three recurrent variants (MSH2 c.943-1G > C, MLH1 c.1358dup and c.2041G > A) accounted for 58.3% (7/12) of all families harboring pathogenic/likely pathogenic MLH1/MSH2 variants. Pathogenic MSH6 variants were not detected. Conclusion Pathogenic/likely pathogenic MLH1/MSH2 variants account for a substantial proportion of CRC patients with HNPCC/suspected-HNPCC in Pakistan. Our findings suggest that HNPCC/suspected-HNPCC families should be tested for these recurrent variants prior to comprehensive gene screening in this population.

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