Colorectal Cancer In First-degree Relatives Research Articles

Association of inflammatory bowel disease in first-degree relatives with risk of colorectal cancer: A nationwide case-control study in Sweden.

This study aims to assess the association between inflammatory bowel disease (IBD) history in first-degree relatives (FDRs) and colorectal cancer (CRC) risk. We conducted a nationwide case-control study in Sweden among 69 659 CRC cases and 343 032 non-CRC controls matched on age, sex, birth year and residence county. Through linkage of multi-generation register and the nationwide ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort, we ascertained IBD diagnoses among parents, full siblings and offspring of the index individuals. Odds ratios (ORs) of CRC associated with IBD family history were calculated using conditional logistic regression. 2.2% of both CRC cases (1566/69659) and controls (7676/343027) had ≥1 FDR with IBD history. After adjusting for family history of CRC, we observed no increased risk of CRC in FDRs of IBD patients (OR, 0.96; 95%CI, 0.91-1.02). The null association was consistent according to IBD subtype (Crohn's disease or ulcerative colitis), number of FDRs with IBD (1 or ≥ 2), age at first IBD diagnosis in FDRs (<18, 18-39, 40-59 or ≥60 years), maximum location/extent of IBD or FDR relation (parent, sibling or offspring). The null association remained for early-onset CRC (diagnosed at age <50 years). In conclusion, IBD history in FDRs was not associated with an increased risk of CRC. Our findings suggest that extra screening for CRC may not be needed in the offspring, siblings or parents of IBD patients, and strengthen the theory that it is the actual inflammation or atypia of the colon in IBD patients that confers the increased CRC risk.

The comparison of risk factors for colorectal neoplasms at different anatomical sites

AimBoth the clinical manifestation and molecular characteristics of colorectal cancer (CRC) vary according to the anatomical site. We explored the risk factors for four groups of colorectal neoplasms (CRN) at different anatomical sites.MethodsWe extracted data from the database of Tianjin Colorectal Cancer Screening Program from 2010 to 2020. According to the CRN anatomical sites, patients were divided into four groups: the proximal colon group, the distal colon group, the rectum group, and the multiple colorectal sites. Binary logistic regression analysis was used to explore the differences in risk factors of CRN at different anatomical sites.ResultsThe numbers of patients with CRN in the proximal colon, distal colon, rectum, and multiple colorectal sites were 4023, 6920, 3657, and 7938, respectively. Male sex was associated with a higher risk from the proximal colon to the rectum. Advanced age and obesity were also significantly associated with overall colorectal CRN risk, but there were some differences between men and women. Smoking was associated with CRN risk only in the distal colon and rectum in both men and women. Frequent alcohol consumption and family history of CRC in first-degree relatives (FDRs) were associated with the risk of multisite colorectal CRN only in males.ConclusionsWe observed differences in advanced age, obesity, smoking, alcohol consumption, and family history of colorectal cancer at different anatomical sites of colorectal neoplasms. These factors vary by gender.

Risk Scoring Systems for Predicting the Presence of Colorectal Neoplasia by Fecal Immunochemical Test Results in Chinese Population.

Adherence to colonoscopy screening for colorectal cancer (CRC) is low in general populations, including those tested positive in the fecal immunochemical test (FIT). Developing tailored risk scoring systems by FIT results may allow for more accurate identification of individuals for colonoscopy. Among 807,109 participants who completed the primary tests in the first-round Shanghai CRC screening program, 71,023 attended recommended colonoscopy. Predictors for colorectal neoplasia were used to develop respective scoring systems for FIT-positive or FIT-negative populations using logistic regression and artificial neural network methods. Age, sex, area of residence, history of mucus or bloody stool, and CRC in first-degree relatives were identified as predictors for CRC in FIT-positive subjects, while a history of chronic diarrhea and prior cancer were additionally included for FIT-negative subjects. With an area under the receiver operating characteristic curve of more than 0.800 in predicting CRC, the logistic regression-based systems outperformed the artificial neural network-based ones and had a sensitivity of 68.9%, a specificity of 82.6%, and a detection rate of 0.24% by identifying 17.6% subjects at high risk. We also reported an area under the receiver operating characteristic curve of about 0.660 for the systems predicting CRC and adenoma, with a sensitivity of 57.8%, a specificity of 64.6%, and a detection rate of 6.87% through classifying 38.1% subjects as high-risk individuals. The performance of the scoring systems for CRC was superior to the currently used method in Mainland, China, and comparable with the scoring systems incorporating the FIT results. The tailored risk scoring systems may better identify high-risk individuals of colorectal neoplasia and facilitate colonoscopy follow-up. External validation is warranted for widespread use of the scoring systems.

Colorectal cancer risk in association with colorectal cancer as a second malignancy in relatives: a nationwide cohort study

BackgroundIncreasing number of individuals will have first-degree relatives (FDRs) diagnosed with colorectal cancer (CRC), as a second primary malignancy (CRCa-2) after a non-CRC cancer. We aimed to estimate whether and to what extent a family history of CRCa-2 is associated with an increased CRC risk.MethodsIn this Swedish nationwide cohort study, rate ratio (RR) and cumulative incidence of CRC were estimated among 172,531 individuals with a family history of CRC as a first primary malignancy (CRCa-1) and 17,830 with a family history of CRCa-2, respectively, using individuals without cancer family history as the reference group.ResultsA cumulative incidence of CRC by age 80 was 6.3 and 5.6% for individuals with a parental and a sibling family history of CRCa-2, respectively. RRs of CRC for one FDR diagnosed with CRCa-1 and CRCa-2 were respectively 1.72 (95% CI, 1.65–1.79) and 1.50 (1.32–1.70); the latter RR was lower than the former (P = 0.0356), but no difference was observed after adjusting age of diagnosis of CRC in FDR and family relationship (P = 0.6898). Increased RRs were found to be associated with a CRCa-2 diagnosis in FDR that occured after cancers in upper aerodigestive tract, breast, prostate, kidney and nervous system.ConclusionsIndividuals who have relatives with CRCa-2 have an increased risk of CRC, but the magnitude is lower than those having relatives with CRCa-1, which is related to different ages of diagnosis of CRC in FDR and family relationships.

Improved risk scoring systems for colorectal cancer screening in Shanghai, China

BackgroundAn optimal risk‐scoring system enables more targeted offers for colonoscopy in colorectal cancer (CRC) screening. This analysis aims to develop and validate scoring systems using parametric and non‐parametric methods for average‐risk populations.MethodsScreening data of 807,695 subjects and 2806 detected cases in the first‐round CRC screening program in Shanghai were used to develop risk‐predictive models and scoring systems using logistic‐regression (LR) and artificial‐neural‐network (ANN) methods. Performance of established scoring systems was evaluated using area under the receiver operating characteristic curve (AUC), calibration, sensitivity, specificity, number of high‐risk individuals and potential detection rates of CRC.ResultsAge, sex, CRC in first‐degree relatives, chronic diarrhoea, mucus or bloody stool, history of any cancer and faecal‐immunochemical‐test (FIT) results were identified as predictors for the presence of CRC. The AUC of LR‐based system was 0.642 when using risk factors only in derivation set, and increased to 0.774 by further incorporating one‐sample FIT results, and to 0.808 by including two‐sample FIT results, while those for ANN‐based systems were 0.639, 0.763 and 0.805, respectively. Better calibrations were observed for the LR‐based systems than the ANN‐based ones. Compared with the currently used initial tests, parallel use of FIT with LR‐based systems resulted in improved specificities, less demands for colonoscopy and higher detection rates of CRC, while parallel use of FIT with ANN‐based systems had higher sensitivities; incorporating FIT in the scoring systems further increased specificities, decreased colonoscopy demands and improved detection rates of CRC.ConclusionsOur results indicate the potentials of LR‐based scoring systems incorporating one‐ or two‐sample FIT results for CRC mass screening. External validation is warranted for scaling‐up implementation in the Chinese population.

Lynch-like Syndrome: Potential Mechanisms and Management.

Simple SummaryLynch-like syndrome (LLS) is defined as colorectal cancer cases with microsatellite instability (MSI) and loss of expression of MLH1, MSH2, MSH6, or PMS2 by immunohistochemistry (IHC) in the absence of a germline mutation in these genes that cannot be explained by BRAF mutation or MLH1 hypermethylation. The application of the universal strategy for the diagnosis of Lynch syndrome (LS) in all CRCs is leading to an increase in the incidence of cases of LLS. It has been described that risk of cancer in relatives of LLS patients is in between of that found in Lynch syndrome families and sporadic cases. That makes LLS patients and their families a challenging group for which the origin of CRC is unknown, being a mixture between unidentified hereditary CRC and sporadic cases. The potential causes of LLS are discussed in this review, as well as methods for identification of truly hereditary cases.Lynch syndrome is an autosomal dominant disorder caused by germline mutations in DNA mismatch repair (MMR) system genes, such as MLH1, MSH2, MSH6, or PMS2. It is the most common hereditary colorectal cancer syndrome. Screening is regularly performed by using microsatellite instability (MSI) or immunohistochemistry for the MMR proteins in tumor samples. However, in a proportion of cases, MSI is found or MMR immunohistochemistry is impaired in the absence of a germline mutation in MMR genes, BRAF mutation, or MLH1 hypermethylation. These cases are defined as Lynch-like syndrome. Patients with Lynch-like syndrome represent a mixture of truly hereditary and sporadic cases, with a risk of colorectal cancer in first-degree relatives that is between the risk of Lynch syndrome in families and relatives of sporadic colon cancer cases. Although multiple approaches have been suggested to distinguish between hereditary and sporadic cases, a homogeneous testing protocol and consensus on the adequate classification of these patients is still lacking. For this reason, management of Lynch-like syndrome and prevention of cancer in these families is clinically challenging. This review explains the concept of Lynch-like syndrome, potential mechanisms for its development, and methods for adequately distinguishing between sporadic and hereditary cases of this entity.

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

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. 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. 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. 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.

Risk of Colorectal Cancer in Inflammatory Bowel Disease: Prevention and Monitoring Strategies According With Risk Factors

Colorectal cancer (CRC) is slightly increased in inflammatory bowel disease (IBD) patients, with roughly a 2.5-fold increase compared to the general population. Clinical features associated to CRC risks are extent and severity of colonic involvement, disease duration, concomitant primary sclerosing cholangitis (PSC) and/or familial history of CRC in first-degree relatives. Colonic Crohn’s disease (CD) and ulcerative colitis (UC) share similar risks when similar colonic extent is affected. Risk stratification affects outcomes and surveillance programs.Newer endoscopic techniques substantially ameliorated diagnostic performance of endoscopy, and nowadays the standard for CRC surveillance in IBD patients is high-definition endoscopy, with dye-spray or virtual colonoscopy, oriented at targeted (+ random) colonic biopsies.Visible dysplastic lesions should be considered for endoscopic resection, while invisible dysplasia is still a mandatory proctocolectomy indication.Newer endoscopic interventional techniques (endoscopic mucosa resection, EMR, and endoscopic submucosal dissection, ESD) are appropriate therapeutic techniques to be delivered, but long-term risks of cancer should be balanced towards proctocolectomy.

Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome.

Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC patients develop mismatch repair deficiency without germline pathogenic mutation, known as Lynch-like syndrome (LLS). We compared the risk of CRC in first-degree relatives (FDRs) in LLS and LS patients. LLS was diagnosed when tumors showed immunohistochemical loss of MSH2, MSH6, and PMS2; or loss of MLH1 with BRAF wild type; and/or no MLH1 methylation and absence of pathogenic mutation in these genes. CRC and other LS-related neoplasms were followed in patients diagnosed with LS and LLS and among their FDRs. Standardized incidence ratios (SIRs) were calculated for CRC and other neoplasms associated with LS among FDRs of LS and LLS patients. In total, 205 LS (1205 FDRs) and 131 LLS families (698 FDRs) had complete pedigrees. FDRs of patients with LLS had a high incidence of CRC (SIR, 2.08; 95% confidence interval (CI), 1.56–2.71), which was significantly lower than that in FDRs of patients with LS (SIR, 4.25; 95% CI, 3.67–4.90; p < 0.001). The risk of developing other neoplasms associated with LS also increased among FDR of LLS patients (SIR, 2.04; 95% CI, 1.44–2.80) but was lower than that among FDR of patients with LS (SIR, 5.01, 95% CI, 4.26–5.84; p < 0.001). FDRs with LLS have an increased risk of developing CRC as well as LS-related neoplasms, although this risk is lower than that of families with LS. Thus, their management should take into account this increased risk.

Candida albicans culture from a rectal swab can be associated with newly diagnosed colorectal cancer.

Plenty of metagenomic studies have suggested possible associations between microbiome composition and colorectal cancer (CRC). However, these techniques are not economic enough for routine use so far. Therefore, we explored the possibility to detect species associated with colorectal cancer by conventional culture from rectal swab. Fifty-two patients newly diagnosed for adenoma/CRC and 52 age-matched controls were recruited and sampled. Rectal swabs were inoculated on several types of plates and incubated appropriately under both aerobic and anaerobic conditions. All colonial morphotypes were subcultured and identified using MALDI-ToF MS. Although no bacterial species was significantly associated with CRC in our study, we surprisingly observed a strong and significant overrepresentation of the yeast Candida albicans in cases (P = 0.0066, odds ratio 5.444 [95% CI 1.449-20.462]). Potential confounding factors were associated neither with CRC (history of CRC in first-degree relatives, a personal history of appendectomy and cholecystectomy, increased BMI (body mass index), and the percentage of males) nor with C. albicans presence (preexisting diabetes and PPI medication) in our cohort. A growing body of evidence supports the view that C. albicans does cause cancer in humans. We hypothesize that presence of C. albicans in the gut may induce or facilitate some part of the sporadic CRC cases. Our observation should be a strong incentive to verify the potential usefulness of the easily culturable C. albicans yeast as a screening marker for patients at risk of CRC or those suffering an early asymptomatic stage of CRC.

Family history of colorectal cancer and prevalence of advanced colorectal neoplasia in asymptomatic screened populations in different age groups

The clinical significance of a family history (FH) of colorectal cancer (CRC) in first-degree relatives (FDRs) in CRC screening stratified by different age groups of screened individuals is not fully understood. We investigated the relationship between FH and the presence of advanced colorectal neoplasia (ACN) in screened individuals in different age groups. Data from screened individuals aged 40 to 54 years (n= 2263) and 55 to 69 years (n= 2621) who underwent their first-ever screening colonoscopy were analyzed. The relationship between FH and ACN was examined, and a multivariate logistic regression analysis incorporating other baseline characteristics was performed. Among individuals aged 40 to 54 years, the prevalence of ACN was significantly higher in 249 individuals with affected FDRs than in those without (5.6% vs 1.6%; P< .01), with an adjusted odds ratio of 3.7 (95% confidence interval, 1.9-7.0; P< .01); the prevalence was particularly high in those having FDRs with CRC mortality (7.3%). Among individuals aged 55 to 69 years, the prevalence of ACN was not significantly different between 291 individuals with affected FDRs and those without (5.8% vs 5.8%; P= .95); however, individuals with 2 FDRs with CRC and mortality showed a high prevalence of ACN (17.4% and 42.9%, respectively). An FH of CRC in FDRs was associated with a higher prevalence of ACN in younger individuals, with a particularly high impact of FH of CRC mortality. In contrast, the impact of FH was weaker in older individuals except those having 2 FDRs with CRC or mortality.

Hereditary or Not? Understanding Serrated Polyposis Syndrome.

To present the current understanding of the diagnosis, management, and potential genetic causes of serrated polyposis syndrome. The clinical criteria for serrated polyposis syndrome was recently updated and now includes individuals with five or more serrated polyps proximal to the rectum that are 5 mm in size or greater and at least two that are 10 mm in size of greater as well as individuals with 20 or more serrated polyps throughout the colon with at least five proximal to the rectum. There is a significant risk for colon cancer in first-degree relatives of individuals with serrated polyposis syndrome. However, less than 3% of serrated polyposis syndrome cases are explained by identifiable germline mutations, with mutations in RNF43 being the only currently validated genetic cause. Serrated polyposis syndrome is rarely explained by identifiable germline mutations, but there remains an increased risk for colorectal cancer in first-degree relatives. Referral for genetic counseling and testing is recommended for individuals with serrated polyposis syndrome and a personal history of coexisting adenomatous polyposis or with a concerning family history and can be considered for all individuals with serrated polyposis syndrome. Close endoscopic surveillance of those with serrated polyposis syndrome and their first-degree relatives is recommended. Continued efforts at identifying hereditary causes of serrated polyposis are needed.

Quantitative risk of positive family history in developing colorectal cancer: A meta-analysis.

BACKGROUNDPositive family history is a risk factor for development of colorectal cancer. Despite numerous studies on the topic, the absolute risk in patients with a positive family history remains unclear and therefore studies are lacking to validate non-invasive screening methods in individuals with positive family history.AIMTo quantify the risk of colorectal cancer in individuals with a positive family history.METHODSA comprehensive electronic literature search was performed using PubMed from January 1955 until November 2017, EMBASE from 1947 until 2018, and Cochrane Library without date restrictions. Two independent reviewers conducted study selection, data extraction and quality assessment. A meta-analysis of Mantel-Haenzel relative risks was performed using the random effects model. Newcastle-Ottawa scale was used to score the quality of selected papers. Funnel plot and Egger’s regression test was performed to detect publication bias. Subgroup analysis was performed comparing Asian and non-Asian studies. Sensitivity analyses were performed to rule out the effect of the timing of the study, overall quality, the main outcome and the effect of each individual study in overall result.RESULTSForty-six out of 3390 studies, including 906981 patients were included in the final analysis. 41 of the included studies were case-control and 5 were cohort. A positive family history of colorectal cancer in first-degree relatives was associated with significantly increased risk of colorectal cancer with a relative risk of 1.87 (95%CI: 1.68-2.09; P < 0.00001). Cochrane Q test was significant (P < 0.00001, I2 = 90%). Egger’s regression test showed asymmetry in the funnel plot and therefore the Trim and Fill method was used which confirmed the validity of the results. There was no difference between Asian versus non-Asian studies. Results remained robust in sensitivity analyses.CONCLUSIONIndividuals with a positive family history of colorectal cancer are 1.87 times more likely to develop colorectal cancer. Screening guidelines should pay specific attention to individuals with positive family history and further studies need to be done on validating current screening methods or developing new modalities in this high-risk population.

Impact of family history of colorectal cancer on age-specific prevalence of colorectal neoplasia.

There are no established guidelines on screening strategies for persons with a family history of colorectal cancer (CRC) in Korea. We aimed to evaluate the age-specific risk of colorectal neoplasia according to family history of CRC. Participants who underwent screening colonoscopy were included. Age-specific prevalence of non-advanced adenoma (NAA) and advanced colorectal neoplasia (ACRN) was calculated according to family history of CRC. Among 35997 participants, 1339 (3.7%) had a family history of CRC in first-degree relatives. A family history of CRC was an independent risk factor for NAA (adjusted odds ratio [AOR] 1.33, 95% confidence interval [CI] 1.16-1.52). In the subgroup analysis by age, family history of CRC was a risk factor for NAA in the 50-59 and ≥60years groups (AOR [95% CI]: 1.42 [1.04-1.91] and 2.33 [1.34-4.09], respectively), but not in the 30-39 and 40-49years groups. In the curve of age-specific prevalence of NAA, the gap of the prevalence between the family history and non-family history groups began to widen after the mid-50s. In cases of ACRN, a family history of CRC was not a risk factor in the entire age group (AOR 1.16, 95% CI 0.75-1.70). In the curve of age-specific prevalence of ACRN, however, the gap of the prevalence between the family history and non-family history groups began to widen after the early 60s. Although a family history of CRC is a risk factor for NAA, it may affect NAA development from the mid-50s and ACRN development from the early 60s.

Family history of colorectal cancer in first-degree relatives and metachronous colorectal adenoma.

Little is known about the relationship between having a first-degree relative (FDR) with colorectal cancer (CRC) and risk for metachronous colorectal adenoma (CRA) following polypectomy. We pooled data from seven prospective studies of 7697 patients with previously resected CRAs to quantify the relationship between having a FDR with CRC and risk for metachronous adenoma. Compared with having no family history of CRC, a positive family history in any FDR was significantly associated with increased odds of developing any metachronous CRA (OR = 1.14; 95% CI = 1.01-1.29). Higher odds of CRA were observed among individuals with an affected mother (OR = 1.27; 95% CI = 1.05-1.53) or sibling (OR = 1.34; 95% CI = 1.11-1.62) as compared with those without, whereas no association was shown for individuals with an affected father. Odds of having a metachronous CRA increased with number of affected FDRs, with ORs (95% CIs) of 1.07 (0.93-1.23) for one relative and 1.39 (1.02-1.91) for two or more. Younger age of diagnosis of a sibling was associated with higher odds of metachronous CRA, with ORs (95% CIs) of 1.66 (1.08-2.56) for diagnosis at <54 years; 1.34 (0.89-2.03) for 55-64 years; and 1.10 (0.70-1.72) for >65 years (p-trend = 0.008). Although limited by sample size, results for advanced metachronous CRA were similar to those for any metachronous CRA. A family history of CRC is related to a modestly increased odds of metachronous CRA. Future research should explore whether having a FDR with CRC, particularly at a young age, should have a role in risk stratification for surveillance colonoscopy.

Associations of defect mismatch repair genes with prognosis and heredity in sporadic colorectal cancer

BackgroundMicrosatellite instability arises due to defect mismatch repair (MMR) and occurs in 10–20% of sporadic colorectal cancer. The purpose was to investigate correlations between defect MMR, prognosis and heredity for colorectal cancer in first-degree relatives. Material and methodsTumour tissues from 318 patients consecutively operated for colorectal cancer were analysed for immunohistochemical expression of MLH1, MSH2 and MSH6 on tissue microarrays. Information on KRAS and BRAF mutation status was available for selected cases. ResultsForty-seven (15%) tumours displayed MSI. No correlation was seen between patients exhibiting MSI in the tumour and heredity (p = 0.789). Patients with proximal colon cancer and MSI had an improved cancer-specific survival (p = 0.006) and prolonged time to recurrence (p = 0.037). In a multivariate analysis including MSI status, gender, CEA, vascular and neural invasion, patients with MSS and proximal colon cancer had an impaired cancer-specific survival compared with patients with MSI (HR, 4.32; CI, 1.46–12.78). The same prognostic information was also seen in distal colon cancer; no recurrences seen in the eight patients with stages II and III distal colon cancer and MSI, but the difference was not statistically significant. ConclusionNo correlation between MSI and heredity for colorectal cancer in first-degree relatives was seen. Patients with MSI tumours had improved survival.

Tu1080 Family History of Colorectal Cancer in First-degree Relatives and Metachronous Adenoma in the Pooling Study

Tu1080 Family History of Colorectal Cancer in First-degree Relatives and Metachronous Adenoma in the Pooling Study

Colorectal cancer screening in the familial risk population: Is colonoscopy still the strategy of choice?

First-degree relatives of patients with colorectal cancer (CRC) are at high risk of this disease. For this reason, medical organizations and clinical guidelines recommend more intensive screening and surveillance for such first-degree relatives than for the average-risk population. Colonoscopy has been the cornerstone of CRC screening in this setting. Although colonoscopy is the most sensitive technique for the detection of neoplastic lesions (especially non-advanced adenomas), its role is less clear for CRC. In addition, screening colonoscopy has several limitations that may affect the success of a screening campaign, such as poor participant acceptance, the need for skilled endoscopists, participant access to screening colonoscopy, overburdened endoscopy units, potential complications, and procedure-related costs. In addition, recent evidence has cast doubt on the advantage of colonoscopy over other strategies for the detection of advanced neoplastic lesions. Despite being less sensitive in general, other screening methods frequently recommended in the average-risk population may be more acceptable and thus help increase CRC screening uptake. This review discusses recent evidence on the risk of CRC in first-degree relatives, the advantages and disadvantages of each screening technique, participation rates depending on the technique, patient preferences, and barriers to screening.

Increased Risk of Colorectal Cancer Among Family Members of All Ages, Regardless of Age of Index Case at Diagnosis

It is not clear whether familial risk of colorectal cancer (CRC) varies with age of index CRC patients or their relatives. We quantified the risk of CRC in first-degree relatives (FDRs), second-degree relatives, and first-cousin relatives of individuals with CRC, stratified by ages and sexes of index patients and ages of relatives. CRCs diagnosed between 1980 and 2010 were identified from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. Age- and sex-matched CRC-free individuals were selected to form the comparison group. CRC risk in relatives was determined by Cox regression analysis. Of 18,208 index patients diagnosed with CRC, the highest familial risk was observed in FDRs of index CRC patients who were diagnosed at an age younger than 40 years (hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.7-3.79). However, familial risk was increased in FDRs even when the index case was diagnosed with cancer at an advanced age (>80 years; HR, 1.76; 95% CI, 1.59-1.94). Ages of relatives and ages of index cases of CRC each affected familial cancer risk; the highest risk was found in young relatives (<50 years) of individuals with early-onset CRC (<40 years; HR, 7.0; 95% CI, 2.86-17.09). All relatives of individuals with CRC are at increased risk for this cancer, regardless of the age of diagnosis of the index patient. Although risk is greatest among young relatives of early-onset CRC cases, relatives of patients diagnosed at advanced ages also have an increased risk.

Influence of perception of colorectal cancer risk and patient bowel preparation behaviors: a study in minority populations.

BackgroundLarge disparities exist in the utilization rates of screening modalities for colorectal cancer (CRC) in different socioeconomic areas. In this study, we evaluated whether the quality of bowel preparation differed significantly among populations with a high risk of CRC compared with that among the general population after matching for potential confounding factors.MethodsHispanic and African American patients who underwent routine screening or surveillance colonoscopies in an outpatient setting between 2003 and 2013 were included in this retrospective study. Patients who underwent colonoscopies for emergent indications and repeat routine screening colonoscopies because of prior history of inadequate bowel preparation were excluded from this study. The patients were divided into three groups: patients having an average risk of being diagnosed with CRC (group 1); patients having a high risk of being diagnosed with CRC because of a personal history of adenomatous polyps (group 2); and patients having a high risk of being diagnosed with CRC because of a family history of CRC in first-degree relatives (group 3). All the patients were given preprocedural counseling and written instructions for bowel preparation. Data on demographic information, method of bowel preparation, quality of bowel preparation, comorbidities, and prescription medications were collected.ResultsIn all, 834 patients had a “high-risk for CRC” surveillance colonoscopy in view of their personal history of adenomatous polyps and were included in group 2. In total, 250 patients had a “high-risk for CRC” screening colonoscopy in view of their family history of CRC in first-degree relatives and were included in group 3. Further, 1,000 patients were selected to serve as controls (after matching for age, sex and ethnicity) and were included in group 1. Bowel preparation was graded as good, fair, or poor by the endoscopist performing the study. We observed a significantly higher number of good bowel preparations in group 2 and group 3 (P=0.0001) when compared with group 1 (controls) after adjusting for comorbidities and usage of prescription medication that could potentially cause colonic dysmotility. These differences were significant in both Hispanic and African American patients.ConclusionOur study showed that perception of CRC risk significantly influenced the bowel preparation behaviors of patients belonging to minority populations, with a significantly greater number of patients with a high risk of CRC having adequate bowel preparations.