Increased risk of adenomas in individuals with a family history of colorectal cancer: results of a meta-analysis

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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Association of fatty pancreas with increased risk of pancreatic adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16729 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16729-e16729

Author(s):

Bara El Kurdi ◽

Adam Bataineh ◽

Sumbal Babar ◽

Mahmoud El Iskandarani ◽

Mohammad Alomari ◽

...

Keyword(s):

Diabetes Mellitus ◽

Chronic Pancreatitis ◽

Family History ◽

Pancreatic Adenocarcinoma ◽

Meta Analysis ◽

Fatty Infiltration ◽

Diagnostic Approach ◽

Increased Risk ◽

History Of ◽

Meta Regression

e16729 Background: Pancreatic adenocarcinoma (PADC) remains one of the most fatal malignancies with poor outcomes and prognosis. Several risk factors have been associated with its development such as smoking, age, obesity, chronic pancreatitis, diabetes mellitus and a family history of PADC. Furthermore, recent pathologic studies demonstrated that fatty infiltration of the pancreas (FP) is positively correlated with PADC development. We sought to systematically review the literature and perform the first meta-analysis to study the risk of PADC among patients with FP. Methods: We conducted a systematic search of the Pubmed, EMBASE, and Cochrane databases from inception through November-2019 for studies correlating FP with PADC. Relevant data was extracted and analyzed using comprehensive meta-analysis software. Random-effects model was used for all variables. Heterogeneity was assessed using the I2 measure and Cochrane Q-statistic. Publication bias was assessed using Egger’s test. Meta regression models accounting for independent variables such as age, sex, smoking, family history of PADC, chronic pancreatitis and method of FP diagnosis were constructed to explain heterogeneity. Results: Five observational case-control studies published between 2014 and 2019 including a total of 761 patients (320 PADC patients and 441 controls) were included. FP was associated with increased PADC with an OR 4.6 (CI 2.4-8.9) compared to controls with a considerable heterogeneity (I2= 69%). Meta regression analysis accounting for modality used to diagnose FP was able to explain 100% of the noted heterogeneity. Conclusions: While we noted FP to be significantly associated with increased PADC, heterogeneity in FP diagnostic approach resulted in significant inter-study variation. A consensus on a clear definition of FP with a standardized diagnostic approach is needed to better appraise literature on this emerging disease entity. Further prospective studies are needed to validate our results and explore the possible role for PADC screening in FP in addition to known factors such as family history and new-onset diabetes mellitus.

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Family History of Colorectal Adenomatous Polyps and Increased Risk for Colorectal Cancer

Annals of Internal Medicine ◽

10.7326/0003-4819-128-11-199806010-00006 ◽

1998 ◽

Vol 128 (11) ◽

pp. 900 ◽

Cited By ~ 81

Author(s):

Habibul Ahsan

Keyword(s):

Colorectal Cancer ◽

Family History ◽

Adenomatous Polyps ◽

Increased Risk ◽

History Of

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A64 REVIEW OF PATIENTS REFERRED TO THE DIVISION OF DIGESTIVE CARE AND ENDOSCOPY AT DALHOUSIE UNIVERSITY FOR COLORECTAL CANCER SCREENING BASED ON A FAMILY HISTORY OF COLORECTAL CANCER: HOW MANY UNDERWENT COLONOSCOPY?

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.062 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 23-25

Author(s):

M Miles

Keyword(s):

Colorectal Cancer ◽

Family History ◽

High Risk ◽

Average Risk ◽

Cross Sectional ◽

Crc Screening ◽

Increased Risk ◽

Fit Testing ◽

Quality Assessment Study ◽

History Of

Abstract Background Nova Scotia has provincial colorectal cancer (CRC) screening for asymptomatic, average risk individuals age 50–74 using fecal immunochemical testing (FIT) every 2 years. However, individuals with 1 or more first degree relatives (FDR) diagnosed with CRC by age 60 have a 2–4 fold increased risk for developing CRC. For these high risk individuals, current guidelines recommend CRC screening with colonoscopy rather than FIT testing. Annually, the Division of Digestive Care & Endoscopy (DCE) at Dalhousie University receives many referrals for patients with a family history of CRC but the percentage of patients who require this procedure is unclear. Aims The objectives of this quality assessment study were to review patients referred to DCE for a family history of CRC to (1) better understand the indication for referral; and (2) determine the percentage of patients undergoing colonoscopy Methods This was a retrospective cross sectional review of a prospectively updated database. The study population was patients referred to DCE from 2012–2019 based on a family history of CRC, as indicated on the referral. Family history of CRC was defined as 1 or more FDRs diagnosed with CRC. High risk patients were those with 2 or more FDRs with CRC or 1 FDR diagnosed by age 60. All patients were reviewed by a single gastroenterologist in clinic. Results A total of 107 referrals from 2012–2019 were reviewed. Of patients age 50 or older, 51/78 (65.4%) had performed at least 1 FIT. The indications for referral were 2 or more FDR diagnosed with CRC for 6/107 (5.6%) patients, 1 FDR diagnosed with CRC by age 60 for 37/107 patients (34.6%) and 1 FDR diagnosed with CRC over age 60 for 33/107 patients (30.8%). The remaining 31/107 patients (29.0%) had no FDR with CRC. Of the 43/107 patients (40.2%) considered high risk based on family history alone, 34/43 (79.1%) underwent colonoscopy and 8/43 (18.6%) opted for FIT testing. Of the 64/107 patients (59.8%) considered average risk based on family history alone, 26/64 (40.6%) had another indication for colonoscopy and 35/64 (54.7%) resumed FIT testing. Conclusions The majority of patients (71.0%) referred to the DCE for a family history of CRC had at least 1 FDR with CRC. Just over half of patients (55.1%) referred to the DCE for a family history of CRC underwent colonoscopy. Strategies to improve the referral process by better capturing high risk individuals are needed. Funding Agencies None

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Importance of Family History of Colorectal Carcinoma In Situ Versus Invasive Colorectal Cancer: A Nationwide Cohort Study

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2021.7004 ◽

2021 ◽

pp. 1-6

Author(s):

Yu Tian ◽

Elham Kharazmi ◽

Hermann Brenner ◽

Xing Xu ◽

Kristina Sundquist ◽

...

Keyword(s):

Colorectal Cancer ◽

Family History ◽

Colorectal Carcinoma ◽

Carcinoma In Situ ◽

Cumulative Risk ◽

First Degree Relatives ◽

Younger Age ◽

Increased Risk ◽

History Of

Background: The aim of this study was to explore the risk of invasive colorectal cancer (CRC) in relatives of patients with colorectal carcinoma in situ (CCIS), which is lacking in the literature. Patients and Methods: We collected data from Swedish family-cancer datasets and calculated standardized incidence ratio (SIR) and cumulative risk of CRC in family histories of CCIS in first- and second-degree relatives. Family history was defined as a dynamic (time-dependent) variable allowing for changes during the follow-up period from 1958 to 2015. Of 12,829,251 individuals with available genealogical data, 173,796 were diagnosed with CRC and 40,558 with CCIS. Results: The lifetime (0–79 years) cumulative risk of CRC in first-degree relatives of patients with CCIS was 6.5%, which represents a 1.6-fold (95% CI, 1.5–1.7; n=752) increased risk. A similarly increased lifetime cumulative risk (6.7%) was found among first-degree relatives of patients with CRC (SIR, 1.6; 95% CI, 1.6–1.7; n=6,965). An increased risk of CRC was also found in half-siblings of patients with CCIS (SIR, 1.9; 95% CI, 1.1–3.0; n=18) and also in half-siblings of patients with CRC (SIR, 1.7; 95% CI, 1.3–2.1; n=78). Moreover, the increased risk of CRC was higher for younger age at diagnosis of CCIS in the affected first-degree relative and for younger age at diagnosis of CRC in the index person. Conclusions: Results of this study show that first-degree relatives and half-siblings of patients with CCIS have an increased risk of CRC, which is comparable in magnitude to the risk of those with a family history of invasive CRC. These findings extend available evidence on familial risk of CRC and may help to refine guidelines and recommendations for CRC screening.

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Clinical Characteristics Associated With Stuttering Persistence: A Meta-Analysis

Journal of Speech Language and Hearing Research ◽

10.1044/2020_jslhr-20-00096 ◽

2020 ◽

Vol 63 (9) ◽

pp. 2995-3018

Author(s):

Cara M. Singer ◽

Alison Hessling ◽

Ellen M. Kelly ◽

Lisa Singer ◽

Robin M. Jones

Keyword(s):

Family History ◽

Clinical Characteristics ◽

Language Skills ◽

Meta Analysis ◽

Age At Onset ◽

Speech Sound ◽

Receptive Language ◽

Eligibility Criteria ◽

Increased Risk ◽

History Of

Purpose The purpose of this meta-analytic study was to identify clinical characteristics, defined as child factors that can be assessed by a speech-language pathologist as part of a routine speech-language evaluation that may differentiate children who persist in stuttering from children who eventually recover from stuttering. Clinical characteristics explored included sex, age at onset, family history of stuttering, stuttering frequency and severity, speech-language skills, and temperament. Method Studies were identified through electronic databases, journals, and reference lists of relevant reports (e.g., research articles). Eligible studies followed young children who stutter (i.e., under 6 years old) for at least 24 months, assessed a potential clinical marker at study entry, and determined talker group classification (i.e., persistent or recovered) at study completion. Sex and family history differences were estimated using risk ratios; all other differences were estimated using Hedges's g . Heterogeneity and methodological differences among studies were evaluated. Results Eleven studies (41 reports) met eligibility criteria. Persistent children were older at stuttering onset and exhibited higher frequencies of stuttering-like disfluencies, lower speech sound accuracy, and lower expressive and receptive language skills than recovered children. Males and children with a family history of stuttering were also more likely to persist. Conclusions Clinical characteristics were identified that are associated with increased risk for stuttering persistence. Future studies have the potential to translate these clinical characteristics into prognostic markers for stuttering persistence risk.

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Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis

Gastroenterology Research and Practice ◽

10.1155/2019/5363261 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Qing Zhou ◽

Zhao-Feng Shen ◽

Ben-sheng Wu ◽

Cheng-biao Xu ◽

Zhong-qi He ◽

...

Keyword(s):

Colorectal Cancer ◽

Systematic Review ◽

Ulcerative Colitis ◽

English Language ◽

Disease Duration ◽

Meta Analysis ◽

Disease Extent ◽

Increased Risk ◽

History Of ◽

Scientific Meetings

Background. Ulcerative colitis (UC) patients have an increased risk for the development of colorectal cancer (CRC). Our aim was to assess the risk of CRC in UC patients compared with disease extent, disease duration, and geographic variation. Methods. In this systematic review and meta-analysis, we searched PubMed, scientific meetings, and the bibliographies of identified articles, with English language restrictions for studies published from 1988 to 2018, and assessed the risk of CRC in UC patients. Patients with Crohn’s disease, family history of CRC, and colorectal adenomatous polyp (CAP) were excluded from this research. The study was registered with PROSPERO, number CRD42018102213. Findings. We included 58 studies that included 267566 UC patients. Extensive UC and left-sided UC had a higher risk of CRC than proctitis UC. Geography also played a role in UC-associated CRC development. The time of malignant transformation in Asian UC patients started after 10-20 years of this disease duration. North American UC-associated CRC patients significantly increased in more than 30 years of this disease duration. Conclusion. In a systematic review of the literature, we found that disease extent, disease duration, and geography were strong, independent risk factors in UC-associated CRC development.

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Does the Age of Sudden Cardiac Death in Family Members Matter in Brugada Syndrome?

Journal of the American Heart Association ◽

10.1161/jaha.120.019788 ◽

2021 ◽

Author(s):

Pattara Rattanawong ◽

Jakrin Kewcharoen ◽

Chanavuth Kanitsoraphan ◽

Timothy Barry ◽

Anusha Shanbhag ◽

...

Keyword(s):

Family History ◽

Sudden Cardiac Death ◽

Brugada Syndrome ◽

Cardiac Death ◽

Meta Analysis ◽

Positive Family History ◽

Family Members ◽

Increased Risk ◽

History Of ◽

Risk Predictor

Background Brugada syndrome is an inherited cardiac channelopathy associated with major arrhythmic events (MAEs). The presence of a positive family history of sudden cardiac death (SCD) as a risk predictor of MAE remains controversial. We aimed to examine the association between family history of SCD and MAEs stratified by age of SCD with a systematic review and meta‐analysis. Methods and Results We searched the databases of MEDLINE and EMBASE from January 1992 to January 2020. Data from each study were combined using the random‐effects model. Fitted metaregression was performed to evaluate the association between the age of SCD in families and the risk of MAE. Twenty‐two studies from 2004 to 2019 were included in this meta‐analysis involving 3386 patients with Brugada syndrome. The overall family history of SCD was not associated with increased risk of MAE in Brugada syndrome (pooled odds ratio [OR], 1.11; 95% CI, 0.82–1.51; P =0.489, I 2 =45.0%). However, a history of SCD in family members of age younger than 40 years of age did increase the risk of MAE by ≈2‐fold (pooled OR, 2.03; 95% CI, 1.11–3.73; P =0.022, I 2 =0.0%). When stratified by the age of cut point at 50, 45, 40, and 35 years old, a history of SCD in younger family member was significantly associated with a higher risk of MAE (pooled OR, 0.49, 1.30, 1.51, and 2.97, respectively; P =0.046). Conclusions A history of SCD among family members of age younger than 40 years was associated with a higher risk of MAE.

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