Family History Of Colorectal Cancer Research Articles

Personalized Initial Screening Age for Colorectal Cancer in Individuals at Average Risk

Colorectal cancer (CRC) risk varies widely in the population at average risk without a family history, but there are no established routines for translating this variation into personalized starting ages of screening. To illustrate derivation of risk-adapted starting ages of CRC screening based on the concept of risk advancement period (RAP) using sex and a polygenic risk score (PRS) as an example. This cohort study included participants in the UK Biobank study recruited in England, Wales, and Scotland between March 13, 2006, and October 1, 2010. Participants were aged 40 to 69 years, with no previous bowel cancer screening and no family history of CRC. Follow-up of cancer data was completed February 29, 2020, for England and Wales and January 31, 2021, for Scotland. The censoring date for death data was September 30, 2021, for England and Wales and October 31, 2021, for Scotland. Data on age, sex, and family history were collected at the baseline interview. A PRS was calculated based on 139 CRC-related risk loci. Hazard ratios (HRs) of sex and PRS with CRC risk and mortality were estimated using Cox proportional hazards regression models and were translated to RAPs to quantify how many years of age earlier or later men and individuals in higher or lower PRS deciles would reach risks comparable with those of the reference group (ie, women or those in the 5th and 6th PRS deciles). Among 242 779 participants (median age, 55 [IQR, 48-61] years; 55.7% women), 2714 incident CRC cases were identified during a median follow-up of 11.2 (IQR, 10.5-11.8) years and 758 deaths during a median follow-up of 12.8 (IQR, 12.0-13.4) years. The HRs of CRC risk were 1.57 (95% CI, 1.46-1.70) for men vs women and ranged from 0.51 (95% CI, 0.41-0.62) to 2.29 (95% CI, 2.01-2.62) across PRS deciles compared with the reference. The RAPs were 5.6 (95% CI, 4.6-6.6) years for men vs women and ranged from -8.4 (95% CI, -11.0 to -5.9) to 10.3 (95% CI, 8.5-12.1) years across PRS deciles compared with the reference deciles. Risk-adapted starting ages of screening would vary by 24 years between men in the highest PRS decile and women in the lowest PRS decile. Similar results were obtained regarding CRC mortality. In this large cohort study including women and men at average risk of CRC, risk-adapted starting ages of screening strongly varied by sex and a PRS. The RAP concept could easily accommodate additional factors for defining personalized starting ages of screening.

Practice of colorectal cancer screening in the United Arab Emirates and factors associated – a cross-sectional study

BackgroundColorectal cancer is a significant public health concern globally, with high incidence and mortality rates. Despite the implementation of CRC screening guidelines, the uptake of screening among adults in the UAE remains low. This study aimed to assess the practice, factors associated, barriers, and knowledge gaps among adults in the UAE.Materials and methods2100 residents of the UAE, aged > = 40 years, participated in the study. A validated questionnaire was used to collect data. Data was collected through online platforms and face-to-face interviews in healthcare settings. Chi-Square test and binary logistic regression were used for data analysis.ResultsThe study revealed a low CRC screening rate of 9.1%. Factors analyzed included age groups, health insurance coverage, regular physician checkups, family history of CRC, awareness of CRC, and knowledge levels about CRC and its signs and symptoms. Participants in the 50–59 age group showed a slightly higher likelihood of CRC screening, but the difference was not statistically significant. However, individuals in the 60–69 and > = 70 age groups were more likely to undergo screening. Regular physician checkups, family history of CRC, prior knowledge of CRC, and knowledge about the disease and its signs and symptoms were associated with a higher likelihood of screening, with statistically significant OR.ConclusionA low CRC screening rate of 9.1% among adults. Barriers to screening included not being offered a test by physicians, fear of positive results, discomfort with the screening process, perception of pain, and lack of knowledge. Identifying particulate barriers and developing targeted measures requires larger-scale research.

Family history of cancer as a potential risk factor for colorectal cancer in EMRO countries: a systematic review and meta-analysis

The current meta-analysis aims to investigate the existing articles that evaluated the implications of a positive family history of cancer on the risk of colorectal cancer (CRC) within the EMRO countries. We employed PubMed, Scopus, and Web of Science as search databases for this study. To assess the quality of the selected articles, we utilized the Newcastle–Ottawa (NCO) checklist. In comparing the impact of a family history of cancer between the case and control groups, we computed the odds ratio (OR) along with its corresponding 95% confidence interval (CI). Finally, 27 articles were selected for meta-analysis. The result of the meta-analysis showed a significant association between the presence of a family history of CRC or any cancers and CRC (OR 2.21; 95% CI 1.54–3.17; P < 0.001, OR 1.76; 95% CI 1.27–2.42; P = 0.001, respectively). Our findings underscore the critical importance of timely screening and early identification for individuals with a family history of cancer. By fostering close coordination among healthcare facilities and actively promoting the adoption of screening methods for early detection, we have the potential to significantly reduce both mortality rates and financial burdens of CRC on the general public, ultimately leading to enhanced patient outcomes.

The Diagnostic Yield of Genetic Testing in Patients With Multiple Colorectal Adenomas: A Specialist Center Cohort Study.

Adenoma multiplicity is associated with increased colorectal cancer (CRC) risk. The utility of genetic testing in patients with multiple colorectal adenomas (MCRA) remains uncertain. We evaluated the diagnostic yield of mutations in polyposis- and CRC-associated genes in patients with MCRA. We performed a cross-sectional review of adult patients with 10-99 cumulative adenomas from the prospective database at the St Mark's Hospital Polyposis Registry and Family Cancer Clinic between 1999 and 2021. Genetic testing was performed for adenomatous polyposis-associated genes, hamartomatous polyposis-associated genes, and nonpolyposis colorectal cancer-associated genes. Clinicopathological outcomes were extracted for multiple logistic regression analysis. Two hundred fifty-nine patients with MCRA (median age 61 [interquartile range 53-69] years) were identified. Sixty-six patients (25.5%) had a pathogenic variant or likely pathogenic variant, with APC and biallelic MUTYH mutations constituting the majority of identified pathogenic variant/likely pathogenic variants. Diagnostic yields were greater than 10% at any adenoma burden. In univariate analysis, higher adenoma burden and younger age were associated with higher yield (both P < 0.0001). In patients with MCRA with 10-19 adenomas without a relevant personal or family history of CRC, the diagnostic yield was nil. In multiple logistic regression analysis, higher adenoma burden, younger age, personal history of CRC, and first-degree familial history of CRC were associated with higher diagnostic yield. Diagnostic yield of >10% at any adenoma burden supports current guidance for constitutional genetic testing in patients with MCRA, although the low yield in people older than 60 years with 10-19 adenomas suggests that a stratified approach might be appropriate.

Long-term benefits and harms of early colorectal cancer screening in German individuals with familial cancer risk.

Individuals with a family history of colorectal cancer (CRC) may benefit from early screening with colonoscopy or immunologic fecal occult blood testing (iFOBT). We systematically evaluated the benefit-harm trade-offs of various screening strategies differing by screening test (colonoscopy or iFOBT), interval (iFOBT: annual/biennial; colonoscopy: 10-yearly) and age at start (30, 35, 40, 45, 50 and 55 years) and end of screening (65, 70 and 75 years) offered to individuals identified with familial CRC risk in Germany. A Markov-state-transition model was developed and used to estimate health benefits (CRC-related deaths avoided, life-years gained [LYG]), potential harms (eg, associated with additional colonoscopies) and incremental harm-benefit ratios (IHBR) for each strategy. Both benefits and harms increased with earlier start and shorter intervals of screening. When screening started before age 50, 32-36 CRC-related deaths per 1000 persons were avoided with colonoscopy and 29-34 with iFOBT screening, compared to 29-31 (colonoscopy) and 28-30 (iFOBT) CRC-related deaths per 1000 persons when starting age 50 or older, respectively. For iFOBT screening, the IHBRs expressed as additional colonoscopies per LYG were one (biennial, age 45-65 vs no screening), four (biennial, age 35-65), six (biennial, age 30-70) and 34 (annual, age 30-54; biennial, age 55-75). Corresponding IHBRs for 10-yearly colonoscopy were four (age 55-65), 10 (age 45-65), 15 (age 35-65) and 29 (age 30-70). Offering screening with colonoscopy or iFOBT to individuals with familial CRC risk before age 50 is expected to be beneficial. Depending on the accepted IHBR threshold, 10-yearly colonoscopy or alternatively biennial iFOBT from age 30 to 70 should be recommended for this target group.

Lynch Syndrome: Approach from the Gastroenterologist’s Point of View

"Colorectal cancer is one of the main causes of death by cancer in the European Union and in Romania. Lynch Syndrome is an autosomal dominant inherited disease that affects around 3% of all colorectal cancer patients, defined by mutations in the mismatch repair genes (MLH1, MSH2, MSH6, PMS2). Aside from the high risk for colorectal cancer (CRC), they exhibit a high risk for endometrial cancer, ovarian cancer, gastric cancer, pancreatic cancer, brain cancer, small bowel cancer, and sebaceous gland cancer. Diagnosis is often made by the gastroenterologist, usually when he meets a young patient with symptoms suggesting the presence of a colonic tumor and a family history of CRC. The role of the gastroenterologist is to investigate the best practices in order to have an early diagnosis and to prevent interval cancers according to the newest guidelines or other gastrointestinal tract tumors associated with Lynch Syndrome. Registries play an important role in the optimal surveillance of these particular categories of patients and should be put into place in every country. They will allow clinicians to have a better understanding of the disease and a more standardized quality of care for them."

Colorectal Cancer Awareness and Related Factors Among Adults Attending Primary Healthcare in North-Eastern of Iran: A Cross-sectional Study.

Colorectal cancer (CRC) is the third most prevalent cancer in Iran. This study aimed to assess the level of awareness regarding CRC warning signs, risk factors, screening program, and related factors among adults in North-Eastern Iran. Study Design: A cross-sectional study. The multi-stage sampling method was used to survey 2614 participants attending primary healthcare centers in Mashhad, Iran. The data collection tools were the demographics section and Bowel/ CRC Awareness Measure (Bowel/Colorectal CAM). The data were analyzed by SPSS, version 25. The significance level of the data analysis was less than 0.05. Mean awareness for CRC warning signs and CRC risk factors were 2.85±2.13 and 3.63±1.85, respectively. Most participants (97.2%) had no awareness of the CRC screening program. There was a significant association between marital status, education, job, income, and family history of CRC with awareness of warning signs (P<0.001); moreover, there was a significant association between age, education, job, income, and family history of CRC with awareness of risk factors (P<0.001). The results of logistic regression indicated that there was a significant association between age (P=0.022, OR=1.794, 95% confidence interval [CI]: 1.087, 2.962), gender (P=0.005, OR=0.488, 95% CI: 0.296, 0.803) and warning sign awareness (P<0.001, OR=1.278, 95% CI: 1.124, 1.454) with awareness of the CRC screening program. In this study, most of the participants had low awareness of CRC. More aimed educational interventions are needed to promote Iranian adults' awareness of CRC.

Statins, commonly coprescribed drugs, and concomitant risk factors: A protective, neutral, or harmful association with common cancer types development: A 10-year multicentric retrospective lebanese study.

Elevated blood levels of low-density lipoprotein cholesterol are a major cardiovascular risk factor, and cholesterol-lowering drugs are among the most prescribed drugs worldwide. Cancer is the second leading cause of death after cardiovascular diseases. The relationship between cancer development and statins intake is controversial, and there are no clear studies in Lebanon and the Middle East concerning this topic. Hence, our study aimed to search for any possible association of statin intake as well as other medications (proton pump inhibitors [PPI], metformin, Aspirin, Angiotensin-Converting Enzyme inhibitors, and fenofibrate) with lung, colorectal cancer (CRC), and bladder cancer development in the Lebanese population. A retrospective study was performed on 709 subjects divided into 2 main groups: control (no cancer ± statin intake), and cases (either lung, or colorectal, or bladder cancer ± statin intake). Collected data included the age and gender of the patient, socioeconomic status, presence of cardiovascular disease and comorbidities, cancer risk factors, and the intake type, dose, and duration of statins. Bivariate, multivariate, and binary logistic analyses were enrolled. Out of 709 participants, 63.2% were males and 75% were cancer-positive (24.1%: lung cancer, 26.7%: CRC, 24.1%: bladder cancer). The overall intake of statins was not shown to significantly affect cancer development. However, a duration-response relationship was established between Simvastatin and lung cancer (odds ratio [OR]=1.208) as well as bladder cancer (OR=1.189). No significant association was found between each statin and CRC. Although PPIs intake was associated with a possibly harmful effect on lung cancer development (OR=3.42), it revealed a protective association with CRC development (OR=0.38). Other risk factors such as smoking and age were strongly associated (harmful) with lung and bladder cancer development. Physical inactivity and a family history of CRC were each associated with a harmful effect on CRC development. A harmful association with the development of lung and bladder cancer was found with the increasing duration of intake of Simvastatin. Other drugs such as PPIs and specific risk factors were also associated negatively or positively with the development of these 3 cancers. These findings should be validated by further investigations to guide clinicians on optimal treatment options for their patients.

Metabolic-associated fatty liver disease is associated with colorectal adenomas in young and older Korean adults.

Given that the majority of colorectal cancers (CRCs) develop from high-risk adenomas, identifying risk factors for high-risk adenomas is important. The relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and the risk of colorectal adenoma in young adults remains unclear. We aimed to evaluate this relationship in adults <50 (younger) and ≥50 (older) years of age. This cross-sectional study included 184 792 Korean adults (80% <50 years of age) who all underwent liver ultrasound and colonoscopy. Participants were grouped into those with and without MAFLD and classified by adenoma presence into no adenoma, low-risk adenoma, or high-risk adenoma (defined as ≥3 adenomas, any ≥10 mm, or adenoma with high-grade dysplasia/villous features). The prevalence of low- and high-risk adenomas among young and older adults was 9.6% and 0.8% and 22.3% and 4.8%, respectively. MAFLD was associated with an increased prevalence of low- and high-risk adenomas in young and older adults. Young adults with MAFLD had a 1.30 (95% CIs 1.26-1.35) and 1.40 (1.23-1.59) times higher prevalence of low- and high-risk adenomas, respectively, compared to those without MAFLD. These associations were consistent even in lean adults (BMI < 23 kg/m2 ) and those without a family history of CRC. MAFLD is associated with an increased prevalence of low- and high-risk adenomas in Korean adults, regardless of age or obesity status. Whether reducing metabolic risk factors, such as MAFLD, reduces the risk of precancerous lesions and ultimately reduces the risk of early-onset CRC requires further investigation.

The Diagnostic Performance of Fecal Immunochemical Tests for Detecting Advanced Neoplasia at Surveillance Colonoscopy

An increasing burden on health care resources has resulted in a backlog of individuals requiring colonoscopy, with delays in surveillance possibly detrimental for individuals at increased risk of colorectal cancer (CRC). This study investigated the use of a 2-sample fecal immunochemical test (FIT) to establish those most likely to have advanced neoplasia (AN) and in need of prioritized surveillance colonoscopy. This was a prospective study conducted in the tertiary care setting. Participants completed a 2-sample FIT (OC-Sensor, Eiken Chemical Company) within 90 days of surveillance colonoscopy. The sensitivity of FIT for detection of AN (CRC or advanced adenoma) in moderate- and high-risk individuals was determined at fecal hemoglobin thresholds between 2 and 80 μg/g feces. A total of 766 patients were included (median age, 66.1 years [interquartile range, 58.1-72.9]; 49.9% male), with AN detected in 8.6% (66/766, including 5 CRC). For moderate-risk individuals (with prior history of adenoma or a significant family history of CRC), sensitivity of FIT for AN ranged from 73.5% at 2 μg/g feces, to 10.2% at 80 μg/g feces. For high-risk conditions (confirmed/suspected genetic syndromes or prior CRC), sensitivity of FIT was similar, ranging from 70.6% at the lowest positivity threshold of 2 μg/g feces, to 11.8% at 80 μg/g feces. Independent variables in the whole cohort for association with detection of AN at surveillance colonoscopy were age (odds ratio, 1.03; 95% confidence interval, 1.00-1.06) and FIT hemoglobin result ≥10 μg/g feces (odds ratio, 1.81; 95% confidence interval, 1.04-3.16). The use of FIT before surveillance colonoscopy provides clinicians with insights into the risk of AN. This raises the possibility of a method to triage individuals, facilitating the more efficient management of endoscopic resources.

The Genomic Landscape of Colorectal Cancer in the Saudi Arabian Population Using a Comprehensive Genomic Panel.

Next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS in 107 Saudi Arabian patients without a family history of CRC. Approximately 98% of patients had genetic alterations. Frequent mutations were observed in BRCA2 (79%), CHEK1 (78%), ATM (76%), PMS2 (76%), ATR (74%), and MYCL (73%). The APC gene was not included in the panel. Statistical analysis using the Cox proportional hazards model revealed an unusual positive association between poorly differentiated tumors and survival rates (p = 0.025). Although no significant univariate associations between specific mutations or overall mutation rate and overall survival were found, our preliminary analysis of the molecular markers for CRC in a predominantly Arab population can provide insights into the molecular pathways that play a significant role in the underlying disease progression. These results may help optimize personalized therapy when drugs specific to a patient's mutation profile have already been developed.

Low Incidence of Colorectal Advanced Neoplasia During Surveillance in Individuals with a Family History of Colorectal Cancer

BackgroundFamily history of colorectal cancer (CRC) is used to stratify individuals into risk categories which determine timing of initial screening and ongoing CRC surveillance. Evidence for long-term CRC risk following a normal index colonoscopy in family history populations is limited.AimsTo assess the incidence of advanced neoplasia and associated risk factors in a population undergoing surveillance colonoscopies due to family history of CRC.MethodsSurveillance colonoscopy findings were examined in 425 individuals with a family history of CRC, a normal index colonoscopy and a minimum of 10 years of follow-up colonoscopies. Advanced neoplasia risk was determined for three CRC family history categories (near-average, medium and high-risk), accounting for demographics and time after the first colonoscopy.ResultsThe median follow-up was 13.5 years (IQR 11.5–16.0), with an incidence of advanced neoplasia of 14.35% (61/425). The number of affected relatives and age of CRC diagnosis in the youngest relative did not predict the risk of advanced neoplasia (p > 0.05), with no significant differences in advanced neoplasia incidence between the family history categories (p = 0.16). Patients ≥ 60 years showed a fourfold (HR 4.14, 95% CI 1.33–12.89) higher advanced neoplasia risk during surveillance than those < 40 years at index colonoscopy. With each subsequent negative colonoscopy, the risk of advanced neoplasia at ongoing surveillance was reduced.ConclusionsThe incidence of advanced neoplasia was low (14.35%), regardless of the family history risk category, with older age being the main risk for advanced neoplasia. Delaying onset of colonoscopy or lengthening surveillance intervals could be a more efficient use of resources in this population.

Analysis of germline variants in pediatric patients diagnosed with desmoid tumors and nuchal-type fibromas.

Desmoid tumor (DT) is a fibroblastic proliferation arising in soft tissue characterized by localized infiltrative growth with an inability to metastasize but with a tendency to recurrence. Nuchal-type fibromas are benign soft tissue lesions that are usually developed in the posterior neck. The development of these neoplasms can be associated with a hereditary cancer predisposition syndrome, mainly familial adenomatous polyposis (FAP) syndrome caused by APC germline mutations. Gardner syndrome is a variant of FAP characterized by the presence of extracolonic manifestations including soft tissue tumors as DTs and nuchal-type fibromas. However, the development of these tumors could be associated with germline alterations in other genes related to colorectal cancer development. The objective of this study was to analyze germline variants in APC, MUTYH, POLD1 and POLE genes in five pediatric patients diagnosed with DTs or nuchal-type fibromas. We identified two pathogenic variants in the APC gene in two different patients diagnosed with nuchal-type fibroma and DTs and two variants of uncertain significance in POLD1 in two patients diagnosed with nuchal-type fibroma. Two patients had family history of colorectal cancer, however, only one of them showed an APC germline pathogenic variant. The analysis of germline variants and genetic counseling is essential for pediatric patients diagnosed with DTs or nuchal-type fibromas and their relatives.

Refining Risk Factors for Colorectal Cancer in Patients Presenting with Gastrointestinal Complaints: A Cross-Sectional Study

Background: Colorectal cancer (CRC) is a prevalent malignancy with a significant mortality rate. The epidemiology of CRC varies in different societies, and there are many risk factors. Information about epidemiological characteristics and factors associated with this cancer among Persian individuals is scarce. Objectives: We evaluated the frequency of CRC and its risk factors in patients referring to Shahid Rahimi and Shohada-ye Ashayer hospitals in Khorramabad, Iran, in 2017 - 2020. Methods: This was a descriptive-analytical cross-sectional study on 600 patients with gastrointestinal complaints. A researcher-made checklist was applied to collect the demographic characteristics, including age, gender, educational levels, marital status, and data related to the history of inflammatory bowel disease (IBD), smoking status, drug abuse, and family history of CRC. Data were analyzed by SPSS software version 21 at a significance level of 0.05. Results: In this study, 303 out of 600 patients (50.5%) were male, and 297 cases (49.5%) were female. The mean age of the patients was 55.06 ± 20.62 years. There was not a significant relationship between CRC and gender (P = 0.84), age (P = 0.13), history of IBD (P = 0.522), family history of CRC (P = 0.682), educational level (P = 0.37), smoking (P = 0.815), or drug abuse (P = 0.99). However, there was a significant relationship between marital status and CRC (P = 0.049). Conclusions: Latent genetic disorders and environmental risk factors should be considered in the etiology of CRCs. Evaluation of these factors and precise screening of patients based on standard guidelines is crucial.

Use of a mixed-methods approach to develop a guidebook with messaging to encourage colorectal cancer screening among Black individuals 45 and older.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States and disproportionately impacts Black individuals. Here, we describe the mixed-methods approach used to develop a tailored message guidebook to promote CRC screening among Black individuals in the setting of recently updated screening guidelines. This mixed-methods study included 10 in-depth qualitative interviews and 490 surveys in a nationally representative sample of unscreened Black individuals age ≥ 45. Messages were developed based on American Cancer Society (ACS) and National Colorectal Cancer Roundtable (NCCRT) research findings, tested among Black individuals using MaxDiff analytic methods, and reviewed by a multi-sector expert advisory committee of NCCRT members. The most frequently reported screening barrier in all age groups was self-reported procrastination (40.0% in age 45-49, 42.8% for age 50-54, 34.2% for age ≥ 55). Reasons for procrastination varied by age and included financial concerns, COVID-19 concerns, and fear of the test and bowel preparation. Additional screening barriers included lack of symptoms, provider recommendation, and family history of CRC. Most individuals age 45-49 preferred to receive screening information from a healthcare provider (57.5%); however, only 20% reported that a provider had initiated a screening conversation. We identified age-specific barriers to CRC screening and tailored messaging to motivate participation among unscreened Black people age ≥ 45. Findings informed the development of the NCCRT and ACS guidebook for organizations and institutions aiming to increase CRC screening participation in Black individuals.

Risk factors of colorectal cancer – literature review

Introduction and purpose: Colorectal cancer is one of the most common cancers in the world. It is very important to expand knowledge about this disease because it affects millions of people. Better understanding of the disease will help develop better prevention and treatment strategies. The aim of our work is to classify, analyze and describe colorectal cancer risk factors. This article was written based on articles found in the PubMed database.&#x0D; State of knowledge: Colorectal cancer risk factors can be divided into two groups: modifiable and unmodifiable. Modifiable factors include: diet, low physical activity, smoking, alcohol, overweight and obesity. Unmodifiable factors include: age, sex, inflammatory bowel diseases, genetic factors, family history of colorectal cancer. Each of them increases the risk of developing the disease, the risk is the greater the more factors are present simultaneously. Modifiable factors seem to play a greater role in the development of the disease than unmodifable factors.&#x0D; Summary: Studies of colorectal cancer risk factors may help in the development of prevention. It can also facilitate the personalization of preventive examinations and treatment. By influencing modifiable factors, we can reduce the risk of developing the disease, because following the principles of a healthy lifestyle can minimize the risk associated with genetic factors for the development of colorectal cancer.

Single Nucleotide Polymorphisms in the Vitamin D Metabolic Pathway as Survival Biomarkers in Colorectal Cancer.

Several studies have suggested that single nucleotide polymorphisms (SNPs) related to vitamin D metabolism may affect CRC carcinogenesis and survival. The aim of this study was to evaluate the influence of 13 SNPs involved in the vitamin D metabolic pathway on CRC survival. We conducted an observational retrospective cohort study, which included 127 Caucasian CRC patient from the south of Spain. SNPs in VDR, CYP27B1, CYP2R1, CYP24A1, and GC genes were analyzed by real-time polymerase chain reaction. Progression-free survival (PFS) and overall survival (OS) were assessed. Cox regression analysis adjusted for metastasis, age of diagnosis, stage (IIIB, IV or IVB), ECOG score (2-4), lymph node involvement, adjuvant chemotherapy, and no family history of CRC showed that the VDR ApaI (p = 0.036), CYP24A1 rs6068816 (p < 0.001), and GC rs7041 (p = 0.006) were associated with OS in patients diagnosed with CRC, and CYP24A1 rs6068816 (p < 0.001) was associated with PFS adjusted for metastasis, age of diagnosis, stage (IIIB, IV or IVB), ECOG score (2-4), lymph node involvement, adjuvant chemotherapy, and no primary tumor resection. The rest of the SNPs showed no association with CRC survival. Thus, the SNPs mentioned above may have a key role as prognostic biomarkers of CRC.

Accuracy of the Discriminatory Ability of Combined Fecal Microbiota Panel in the Early Detection of Patients with Colorectal Cancer.

Colorectal cancer (CRC) screening and detecting it at an early stage is an effective way to decrease mortality from CRC. Colonoscopy, considered the gold standard (GS) for diagnosing the disease in many countries, has several limitations. Therefore, the main focus of this literature is to investigate the ability of combining candidate gut microbiota for early diagnosis of CRC, both in the presence and absence of GS test outcomes. We analyzed the data derived from a case-control study, including 83 screening colonoscopies conducted on subjects aged 18-92years in Tehran, Iran. The candidate gut microbiota including, ETBF, Enterococcus faecalis, and Porphyromonas gingivalis were quantified in samples using absolute qRT PCR. The Bayesian latent class model (LCM) was employed to combine the values from the multiple bacterial markers in order to optimize the discriminatory ability compared with a single marker. Based on Bayesian logistic regression, we discovered that family history of CRC, physical activity, cigarette smoking, and food diet were all significantly associated with an increased risk of CRC. When comparing ETBF and E. faecalis to P. gingivalis, we have observed that P. gingivalis exhibited greater predictive power in detecting high-risk individuals with CRC. As such, the sensitivity, specificity, and the area under the receiver-operating characteristics curve of combining ETBF, E. faecalis, and P. gingivalis were 98%, 96%, and 0.97, respectively. This study suggests that the combined use of the three markers markedly improves classification performance compared to pairwise combinations, as well as individual markers, both with and without GS test outcomes. Noticeably, the triple composition of the fecal markers may serve as a reliable non-invasive indicator for the early prediction of CRC.

Co-Occurrence of Germline Genomic Variants and Copy Number Variations in Hereditary Breast and Colorectal Cancer Patients.

Hereditary Breast and Ovarian Cancer (HBOC) syndrome is an autosomal dominant disease associated with a high risk of developing breast, ovarian, and other malignancies. Lynch syndrome is caused by mutations in mismatch repair genes predisposing to colorectal and endometrial cancers, among others. A rare phenotype overlapping hereditary colorectal and breast cancer syndromes is poorly characterized. Three breast and colorectal cancer unrelated patients fulfilling clinical criteria for HBOC were tested by whole exome sequencing. A family history of colorectal cancer was reported in two patients (cases 2 and 3). Several variants and copy number variations were identified, which potentially contribute to the cancer risk or prognosis. All patients presented copy number imbalances encompassing PMS2 (two deletions and one duplication), a known gene involved in the DNA mismatch repair pathway. Two patients showed gains covering the POLE2 (cases 1 and 3), which is associated with DNA replication. Germline potentially damaging variants were found in PTCH1 (patient 3), MAT1A, and WRN (patient 2). Overall, concurrent genomic alterations were described that may increase the risk of cancer appearance in HBOC patients with breast and colorectal cancers.

FIT for purpose: study protocol for a randomized controlled trial to personalize surveillance colonoscopy for individuals at elevated risk of colorectal cancer

PurposeThere is increasing demand for colorectal cancer (CRC) surveillance, but healthcare capacity is limited. The burden on colonoscopy resources could be reduced by personalizing surveillance frequency using the fecal immunochemical test (FIT). This study will determine the safety, cost-effectiveness, and patient acceptance of using FIT to extend surveillance colonoscopy intervals for individuals at elevated risk of CRC.MethodsThis multicenter, prospective, randomized controlled trial will invite participants who are scheduled for surveillance colonoscopy (due to a personal history of adenomas or a family history of CRC) and who have returned a low fecal hemoglobin (< 2 μg Hb/g feces; F-Hb) using a two-sample FIT (OC Sensor, Eiken Chemical Company) in the prior 3 years. A total of 1344 individuals will be randomized to either surveillance colonoscopy as scheduled or delayed by 1 or 2 years for individuals originally recommended a 3- or 5-year surveillance interval, respectively. The primary endpoint is incidence of advanced neoplasia (advanced adenoma and/or CRC). Secondary endpoints include cost-effectiveness and consumer acceptability of extending surveillance intervals, determined using surveys and discrete choice experiments.ConclusionThis study will establish the safety, cost-effectiveness, and acceptability of utilizing a low FIT Hb result to extend colonoscopy surveillance intervals in a cohort at elevated risk for CRC. This personalized approach to CRC surveillance will lead to a reduction in unnecessary colonoscopies, increases in healthcare savings, and a better patient experience. Trial registrationRegistration was approved on December 9, 2019 with the Australian New Zealand Clinical Trials Registry ANZCTR 12619001743156.