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Hot Topics of the Day are picked by experts to capture the latest information and publications on public health genomics and precision health for various diseases and health topics. Sources include published scientific literature, reviews, blogs and popular press articles.

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364 hot topic(s) found with the query "Colorectal cancer"

The State of State Biomarker Testing Insurance Coverage Laws
(Posted: May 14, 2024 3PM)

From the article:" There has been a recent push for legislation mandating coverage of “biomarker testing” according to evidence that receipt of such testing can depend on race and ethnicity, age, geography, or site of care. A specific type of biomarker testing for cancer subtypes (ie, “tumor profiling”) is becoming particularly important because many newer cancer therapies target specific mutations (eg, EGFR in non–small cell lung cancer, KRAS in colorectal cancer). Although use of biomarker testing is increasing, barriers to access persist. Cost and lack of insurance coverage are common barriers to testing because insurance coverage varies across commercial payers, Medicare, and Medicaid."

Integration of pathologic characteristics, genetic risk and lifestyle exposure for colorectal cancer survival assessment
J Xin et al, Nature Comm, April 8, 2024 (Posted: Apr 09, 2024 8AM)

From the abstract: "The development of an effective survival prediction tool is key for reducing colorectal cancer mortality. Here, we apply a three-stage study to devise a polygenic prognostic score (PPS) for stratifying colorectal cancer overall survival. Leveraging two cohorts of 3703 patients, we first perform a genome-wide survival association analysis to develop eight candidate PPSs. Further using an independent cohort with 470 patients, we identify the 287 variants-derived PPS (i.e., PPS287) achieving an optimal prediction performance [hazard ratio (HR) per SD?=?1.99, P?=?1.76?×?10-8], accompanied by additional tests in two external cohorts, with HRs per SD of 1.90 (P?=?3.21?×?10-14; 543 patients) and 1.80 (P?=?1.11?×?10-9; 713 patients). Notably, the detrimental impact of pathologic characteristics and genetic risk could be attenuated by a healthy lifestyle, yielding a 7.62% improvement in the 5-year overall survival rate. "

What to Know About Lynch Syndrome
ThedaCare Genetic Counseling, March 2024 (Posted: Apr 01, 2024 9AM)

From the article: " While it is impossible to change our genes, with knowledge comes power. In the case of Lynch syndrome, a genetic condition that can increase a person’s risk for developing colorectal and other types of cancer, that’s especially true. Colorectal Cancer Awareness Month offers a reminder for everyone to examine their risk for colorectal cancer and to explore options for screening, as well as genetic testing, when recommended."

Lynch Syndrome Ups Risk for Colorectal, Other Cancers
E Herlache, Cancer Care, March 2024 (Posted: Mar 23, 2024 6AM)

From the article: "It’s impossible to change our genes, but with knowledge comes power. In the case of Lynch syndrome, a genetic condition that ups people’s risks for developing colorectal and other types of cancer, that’s especially true. Colorectal Cancer Awareness Month offers a reminder for everyone to examine their risk for colorectal cancer and to explore options for screening as well as genetic testing, when warranted. Lynch syndrome puts a person at a higher risk of developing colorectal, uterine, and ovarian cancer. It’s also associated with other cancers, including kidney, stomach, bladder, brain, prostate, and pancreatic cancer. "

Cell-free DNA for Colorectal Cancer Screening.
Y M Dennis Lo et al. N Engl J Med 2024 3 (11) 1047-1050 (Posted: Mar 14, 2024 10AM)

From the article: "A recent study demonstrated the feasibility of using plasma cfDNA to screen for colorectal cancer, but the relatively low sensitivity for the detection of advanced precancerous lesions is a limitation. Moreover, colonoscopy not only detects such lesions with high sensitivity but also permits their immediate removal. The noninvasiveness (relatively speaking) of the plasma cfDNA assay, though, is a feature that seems likely to result in greater uptake than colonoscopy."

Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening.
Thomas F Imperiale et al. N Engl J Med 2024 3 (11) 984-993 (Posted: Mar 14, 2024 10AM)

From the abstract: "In a prospective study, we evaluated a next-generation multitarget stool DNA test in asymptomatic adults 40 years of age or older who were undergoing screening colonoscopy. The next-generation multitarget stool DNA test showed higher sensitivity for colorectal cancer and advanced precancerous lesions than FIT but also showed lower specificity. "

Improving Noninvasive Colorectal Cancer Screening.
John M Carethers et al. N Engl J Med 2024 3 (11) 1045-1046 (Posted: Mar 14, 2024 10AM)

From the article: "Screening for colorectal cancer saves lives. Screening tests have evolved to include stool-based, endoscopic and image-based, and blood-based methods, with minimal thresholds for sensitivity and specificity for colorectal cancer set by the baseline characteristics of FIT. Although multiple tests have been developed over time and vary in cost-effectiveness for colorectal cancer screening, the best screening test is the one that gets completed by the patient. Most of the recommended tests, including the two newer tests assessed in the studies now published in the Journal, improve on the sensitivity and approach the specificity of FIT. "

A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening.
Daniel C Chung et al. N Engl J Med 2024 3 (11) 973-983 (Posted: Mar 14, 2024 10AM)

From the abstract: "We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions. This cfDNA blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions."

Identification of people with Lynch syndrome from those presenting with colorectal cancer in England: baseline analysis of the diagnostic pathway
FE McRonald et al, EJHG, February 15, 2024 (Posted: Feb 15, 2024 9AM)

From the abstract: "Only 44% of CRCs were screened for dMMR; these figures varied over four-fold with respect to geography. Of those CRCs identified as dMMR, only 51% underwent subsequent diagnostic testing. Overall, only 1.3% of patients with colorectal cancer had a germline MMR genetic test performed; up to 37% of these tests occurred outside of NICE guidelines. The low rates of molecular diagnostic testing in CRC support the premise that Lynch syndrome is underdiagnosed, with significant attrition at all stages of the testing pathway. "

Maximizing scarce colonoscopy resources: the crucial role of Stool-Based tests.
Gloria D Coronado et al. J Natl Cancer Inst 2024 2 (Posted: Feb 04, 2024 4PM)

From the abstract: "During the COVID-19 pandemic, health systems, including federally qualified health centers (FQHCs), experienced disruptions in colorectal cancer (CRC) screening. National organizations called for greater use of at-home stool-based testing followed by colonoscopy for those with abnormal test results to limit (in-person) colonoscopy exams to people with acute symptoms, or who were high-risk. This ‘stool-test-first’ strategy may also be useful for adults with low-risk adenomas who are due for surveillance colonoscopy. "

Remembering My Brother Who Died of Cancer January 11, 2024 Georgia Hurst Blog Article
G Hurst, Cure, January 11, 2024 (Posted: Jan 14, 2024 10AM)

From the article: "Today marks what would have been my brother Jimmy's 65th birthday. It's a bittersweet moment filled with both celebration and reflection as I remember the incredible person he was and the battle he faced against colorectal cancer caused by Lynch syndrome. In sharing this story, I hope to raise awareness about Lynch syndrome, honor Jimmy's memory and shed light on the challenges of survivor guilt that often accompany the loss of a loved one due to Lynch syndrome. "

Influence of family history on penetrance of hereditary cancers in a population setting.
Leigh Jackson et al. EClinicalMedicine 2023 11 102159 (Posted: Nov 14, 2023 8AM)

From the abstract: "Women with a pathogenic BRCA1 or BRCA2 variant had an increased risk of breast cancer that was higher in those with a first-degree family history (relative hazard 10.3 and 7.8, respectively) than those without (7.2 and 4.7). Penetrance to age 60 was also higher in those with a family history (44.7%, CI 32.2-59.3 and 24.1%, CI 17.5-32.6) versus those without (22.8%, CI 15.9-32.0 and 17.9%, CI 13.8-23.0). A similar pattern was seen in Lynch syndrome: individuals with a pathogenic MLH1, MSH2 or MSH6 variant had an increased risk of colorectal cancer that was significantly higher in those with a family history (relative hazard 35.6, 48.0 and 9.9) "

Personalized Initial Screening Age for Colorectal Cancer in Individuals at Average Risk.
Xuechen Chen et al. JAMA Netw Open 2023 10 (10) e2339670 (Posted: Oct 27, 2023 9AM)

From the abstract: "How can risk variation in individuals without a family history of colorectal cancer (CRC) be translated into personalized starting ages of screening? In this cohort study of 242?779 participants with no previous screening for and no family history of CRC, derivation of risk-adapted starting ages of screening used 2 major CRC risk indicators, sex and a polygenic risk score (PRS), based on the risk advancement period concept. Risk-adapted starting ages varied by as much as 24 years between men in the highest PRS decile and women in the lowest PRS decile, even among individuals at average risk. "

Multitarget Stool RNA Test for Colorectal Cancer Screening.
Erica K Barnell et al. JAMA 2023 10 (Posted: Oct 24, 2023 2PM)

From the abstract: " What is the performance of the novel multitarget stool RNA (mt-sRNA) test (ColoSense) for individuals 45 years and older undergoing colorectal cancer screening? A pivotal prospective, cross-sectional clinical trial comprising 8920 eligible participants was used to evaluate the sensitivity and specificity of the mt-sRNA test compared with a colonoscopy. The sensitivity of the mt-sRNA test for detecting colorectal cancer was 94%, the sensitivity for detecting advanced adenomas was 46%, and the specificity for no lesions on colonoscopy was 88%."

Molecular disparities in colorectal cancers of White Americans, Alabama African Americans, and Oklahoma American Indians.
Hiroshi Y Yamada et al. NPJ Precis Oncol 2023 8 (1) 79 (Posted: Aug 21, 2023 8AM)

We compared transcriptomic profiles of CRCs of Alabama AAs, Oklahoma AIs, and white people from both states. Compared to CRCs of white people, CRCs of AAs showed (a) higher expression of cytokines and vesicle trafficking toward modulated antitumor-immune activity, and (b) lower expression of the ID1/BMP/SMAD axis, IL22RA1, APOBEC3, and Mucins; and AIs had (c) higher expression of PTGS2/COX2 (an NSAID target/pro-oncogenic inflammation) and splicing regulators, and (d) lower tumor suppressor activities (e.g., TOB2, PCGF2, BAP1).

How the Y chromosome makes some cancers more deadly for men
H Ledford, Nature, June 21, 2023 (Posted: Jun 22, 2023 7AM)

Two studies address cancers that are particularly aggressive in men: colorectal cancer and bladder cancer. One study finds that the loss of the entire Y chromosome in some cells — which occurs naturally as men age — raises the risk of aggressive bladder cancer and could allow bladder tumours to evade detection by the immune system2. The other finds that a particular Y-chromosome gene in mice raises the risk of some colorectal cancers spreading to other parts of the body.

Bayesian risk prediction model for colorectal cancer mortality through integration of clinicopathologic and genomic data.
Melissa Zhao et al. NPJ Precis Oncol 2023 6 (1) 57 (Posted: Jun 11, 2023 8AM)

Routine tumor-node-metastasis (TNM) staging of colorectal cancer is imperfect in predicting survival due to tumor pathobiological heterogeneity and imprecise assessment of tumor spread. We leveraged Bayesian additive regression trees (BART), a statistical learning technique, to comprehensively analyze patient-specific tumor characteristics for the improvement of prognostic prediction. Of 75 clinicopathologic, immune, microbial, and genomic variables in 815 stage II–III patients within two U.S.-wide prospective cohort studies, the BART risk model identified seven stable survival predictors.

The "Scope" of Colorectal Cancer Screening in Lynch Syndrome: Is There an Optimal Interval?
Leah H Biller et al. J Natl Cancer Inst 2023 5 (Posted: May 05, 2023 9AM)

Across all genes related to Lynch syndrome, colonoscopy screening reduces the risk of CRC and improves overall survival among LS carriers, and remains the mainstay of current risk reduction recommendations. What remains less clear are both the optimal age at which to start screening and the best interval between colonoscopy screenings for LS carriers, such that many international professional society guidelines vary with respect to these recommendations.

Exploring the complex relationship between gut microbiota and risk of colorectal neoplasia using bidirectional Mendelian Randomization analysis.
Wanxin Li et al. Cancer Epidemiol Biomarkers Prev 2023 4 (Posted: Apr 29, 2023 3PM)

We find genetic liability to colorectal neoplasia may be associated with abundance of certain microbiota taxa. It is more likely that subset of CRC genetic liability variants changes gut biology by influencing both gut microbiota and CRC risk. This study highlights the need of future complementary studies to explore causal mechanisms linking both host genetic variation with gut microbiome and CRC susceptibility.

Early Detection of Molecular Residual Disease and Risk Stratification for Stage I to III Colorectal Cancer via Circulating Tumor DNA Methylation.
Shaobo Mo et al. JAMA Oncol (Posted: Apr 21, 2023 6AM)

Are longitudinal changes in circulating tumor DNA (ctDNA) methylation effective in monitoring disease progression from molecular residual disease to recurrence? In this cohort study of 299 patients with colorectal cancer, circulating tumor DNA status was evaluated with 6 DNA methylation markers. The presence of ctDNA was strongly associated with recurrence before and after surgery, after adjuvant chemotherapy, and during longitudinal monitoring.

Liquid Biopsy Assessment of Molecular Residual Disease in Localized Colorectal Cancer: Is It Ready for Prime Time?
Juan Ruiz-Bañobre et al. JAMA Oncol (Posted: Apr 21, 2023 6AM)

Over the last few years, the potential of liquid biopsy, specifically the detection of circulating tumor DNA (ctDNA) in blood from patients with advanced and localized tumors, has emerged as a promising strategy to assist in the clinical management of patients with cancer. In the advanced setting, ctDNA is already validated and used in routine clinical practice to identify clinically actionable genomic alterations. In the localized setting, different observational studies involving patients with solid tumors have confirmed a very high risk of recurrence when ctDNA is detected after therapy with curative intent, introducing the concept of molecular residual disease in managing solid tumors.

Evaluating Colonoscopy Screening Intervals in Patients with Lynch Syndrome from a Large Canadian Registry
M Aronson et al, JNCI, March 25, 2023 (Posted: Mar 25, 2023 8AM)

Lynch Syndrome (LS) screening guidelines originally recommended colonoscopy every 1 to 2 years, beginning between the ages of 20-25 years. Recent studies have questioned the benefits of these short screening intervals in preventing colorectal cancer (CRC). A total of 429 patients with LS were identified with median follow-up of 9.2 years, 44 developed CRC. We found a positive trend between shorter screening intervals and the number of adenomas detected during colonoscopy. Any new adenoma detected at screening decreased 10-year CRC incidence by 11.3%. For MLH1 carriers, a screening interval of 1-2 years vs. 2-3 years led to a 20-year cumulative CRC risk reduction of 28% and 14% in females and males.

A common cancer at an uncommon age.
Marios Giannakis et al. Science (New York, N.Y.) 2023 3 (6637) 1088-1090 (Posted: Mar 21, 2023 8AM)

Patients with EOCRC have a higher relative prevalence of inherited predisposition to cancer, with Lynch syndrome being the most common cause. This condition is characterized by deficiency in the DNA mismatch repair pathway that results in high levels of microsatellite instability with an increased number of mutations, which predisposes to CRC and other types of cancer. Although underdiagnosis of Lynch syndrome cases may be a potential contributing factor, this and other high-penetrance pathogenic germline variants do not explain the observed rise of EOCRC.

Immunotherapy Success for Microsatellite Stable Colorectal Cancers-Searching for the Horizon.
Emil Lou et al. JAMA oncology 2023 3 (Posted: Mar 09, 2023 8PM)

The current landscape of treatment of patients with metastatic CRC has evolved significantly during the past decade. The most notable change has been the validation and incorporation of testable genomic markers predictive of potential response to targeted therapies; this tailored approach has led to an improvement in overall survival as well as in quality of life for thousands of patients.

Regorafenib, Ipilimumab, and Nivolumab for Patients With Microsatellite Stable Colorectal Cancer and Disease Progression With Prior Chemotherapy: A Phase 1 Nonrandomized Clinical Trial.
Marwan Fakih et al. JAMA oncology 2023 3 (Posted: Mar 09, 2023 8PM)

Identification of specific susceptibility loci for the early-onset colorectal cancer.
Haoxue Wang et al. Genome medicine 2023 3 (1) 13 (Posted: Mar 04, 2023 8AM)

We identified 49 independent susceptibility loci that were significantly associated with the susceptibility to EOCRC and the diagnosed age of CRC (both P < 5.0×10-4), replicating 3 previous CRC GWAS loci. There are 88 assigned susceptibility genes involved in chromatin assembly and DNA replication pathways, mainly associating with precancerous polyps. Additionally, we assessed the genetic effect of the identified variants by developing a PRS model.

Codon-specific KRAS mutations predict survival benefit of trifluridine/tipiracil in metastatic colorectal cancer.
Joris van de Haar et al. Nature medicine 2023 3 (Posted: Mar 03, 2023 8AM)

Genomics has greatly improved how patients with cancer are being treated; however, clinical-grade genomic biomarkers for chemotherapies are currently lacking. Using whole-genome analysis of 37 patients with metastatic colorectal cancer (mCRC) treated with the chemotherapy trifluridine/tipiracil (FTD/TPI), we identified KRAS codon G12 (KRASG12) mutations as a potential biomarker of resistance.

Risk assessment for colorectal cancer via polygenic risk score and lifestyle exposure: a large-scale association study of East Asian and European populations.
Junyi Xin et al. Genome medicine 2023 1 (1) 4 (Posted: Jan 25, 2023 8AM)

Using the UK Biobank cohort, we further validated a significant dose-response effect of PRSCSx on incident colorectal cancer, in which the risk was 2.11- and 3.88-fold higher in individuals with intermediate and high PRSCSx than in the low score subgroup (Ptrend = 8.15 × 10-53). Notably, the detrimental effect of being at a high genetic risk could be largely attenuated by adherence to a favorable lifestyle, with a 0.53% reduction in 5-year absolute risk.

Comparative Effectiveness of Immune Checkpoint Inhibitors vs Chemotherapy in Patients With Metastatic Colorectal Cancer With Measures of Microsatellite Instability, Mismatch Repair, or Tumor Mutational Burden.
Quintanilha Julia C F et al. JAMA network open 2023 1 (1) e2252244 (Posted: Jan 24, 2023 8AM)

What is the comparative effectiveness of first-line immune checkpoint inhibitors (ICIs) vs chemotherapy in standard practice settings among patients with metastatic colorectal cancer (MCRC) with high microsatellite instability (MSI-H) determined by next-generation sequencing (NGS)? In this comparative effectiveness research study of 138 patients with MCRC and MSI-H, patients receiving first-line ICIs vs chemotherapy had significantly more favorable time to next treatment, progression-free survival, and overall survival outcomes.

Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer.
Kotani Daisuke et al. Nature medicine 2023 1 (Posted: Jan 17, 2023 9AM)

We report results from GALAXY, which is an observational arm of the ongoing CIRCULATE-Japan study (UMIN000039205) that analyzed presurgical and postsurgical ctDNA in patients with stage II–IV resectable CRC (n?=?1,039). In this cohort, with a median follow-up of 16.74 months (range 0.49–24.83 months), postsurgical ctDNA positivity (at 4?weeks after surgery) was associated with higher recurrence risk (hazard ratio (HR) 10.0, P?<?0.0001) and was the most significant prognostic factor associated with recurrence risk in patients with stage II or III CRC (HR 10.82, P?<?0.001).

Improved two-step testing of genome-wide gene–environment interactions
ES Kawagushi et al, Genetic Epidemiology, December 26, 2022 (Posted: Dec 26, 2022 11AM)

We introduce a new significance-based allocation into bins for Step-2 testing that overcomes the displacement issue and propose a computationally efficient approach to account for multiple testing within bins. Simulation results demonstrate that these simple improvements can provide substantially greater power than current methods under several scenarios. An application to a multistudy collaboration for understanding colorectal cancer reveals a G?×?Sex interaction located near the SMAD7 gene.

Assessment of Body Mass Index, Polygenic Risk Score, and Development of Colorectal Cancer.
Chen Xuechen et al. JAMA network open 2022 12 (12) e2248447 (Posted: Dec 23, 2022 6PM)

Do associations of excess weight with development of colorectal cancer differ by polygenic risk for colorectal cancer (CRC)? In this case-control study including 9169 participants (5053 CRC cases, 4116 controls), associations of excess weight with risk of CRC were independent of polygenic risk for CRC. The association of obesity with CRC risk was equivalent to that of having a 41-percentiles higher polygenic risk score. The findings of this study could contribute to enhanced quantification and communication of the association of excess weight with CRC.

Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C
R Yaeger et al, NEJM, December 21, 2022 (Posted: Dec 22, 2022 8AM)

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries.
Fernandez-Rozadilla Ceres et al. Nature genetics 2022 12 (Posted: Dec 21, 2022 1PM)

We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC.

Integrating genome-wide polygenic risk scores and non-genetic risk to predict colorectal cancer diagnosis using UK Biobank data: population based cohort study
SEW Briggs et al, BMJ, November 2022 (Posted: Nov 14, 2022 7AM)

Integrating polygenic risk scores with QCancer-10 modestly improves risk prediction over use of QCancer-10 alone. Given that QCancer-10 data can be obtained relatively easily from health records, use of polygenic risk score in risk stratified population screening for colorectal cancer currently has no clear justification. The added benefit, cost effectiveness, and acceptability of polygenic risk scores should be carefully evaluated in a real life screening setting before implementation in the general population.

Comparison of Germline Genetic Testing Before and After a Medical Policy Covering Universal Testing Among Patients With Colorectal Cancer
C Moretz et al, JAMA Network Open, October 24, 2022 (Posted: Oct 24, 2022 0PM)

In a cohort study of 9066 patients with CRC in 2017 to 2020, 2288 (25.2%) did not receive MSI/IHC despite being eligible for coverage. In a cohort of 55?595 patients with CRC diagnosed in 2020 and covered by insurance, 1675 (3.0%) received GGT, and 1 in 6 patients had variants that were clinically actionable. These results indicate that medical policies that provide universal testing for MSI/IHC tumor screening and GGT were underused for patients with CRC, potentially impeding their access to precision therapy, clinical trials, and evidence-based clinical management.

An updated counseling framework for moderate-penetrance colorectal cancer susceptibility genes
KE Breen et al, Genetics in Medicine, October 12, 2022 (Posted: Oct 12, 2022 9AM)

When an individual at average risk would initiate colonoscopy at age 45 years, a CRC risk of 0.39% is reached. For CHEK2 1100delC, CHEK2 I157T, and APC I1307K heterozygotes, this same level of risk is reached (or nearly reached) by age 40 to 45 years. For individuals with a monoallelic MUTYH variant, the CRC risk is 0.46% by age 45 to 49 years, similar to individuals at average risk. These updated calculations support recommendations to initiate earlier colonoscopy surveillance for CHEK2 and APC I1307K germline variant heterozygotes. However, earlier surveillance is not indicated for individuals with monoallelic MUTYH germline variants in the absence of family history.

DNA Methylation Profile in CpG-depleted Regions Uncovers a High-Risk Subtype of Early-stage Colorectal Cancer.
Yu Huichuan et al. Journal of the National Cancer Institute 2022 9 (Posted: Oct 02, 2022 8AM)

We demonstrated the prognostic significance of DNA methylation profile in CpG-depleted region, which may serve as a valuable source for tumor biomarkers. MePEC could identify an epigenetic subtype with high risk of recurrence and improve the prognostic accuracy of current clinical variables in early-stage CRC.

A Methylation-Based Prognostic Signature in Stage II Colorectal Patients: Considerations for Clinical Adoption.
Romesser Paul B et al. Journal of the National Cancer Institute 2022 9 (Posted: Oct 02, 2022 8AM)

A biomarker of response to therapy in metastatic BRAFV600E colorectal cancers
Nature Research Briefing, September 14, 2022 (Posted: Sep 15, 2022 6AM)

Colorectal cancers expressing the mutant BRAFV600E comprise 10% of all metastatic colorectal cancers, present with a poor prognosis, and are refractory to common therapies. We discovered that a subgroup of these tumors that carries loss-of-function RNF43 mutations is associated with significantly improved response to the current standard-of-care anti-BRAF–anti-EGFR combination therapy.

Genetic Testing Challenges in Oncology: Lynch Syndrome Diagnosis Despite Negative Test Results
T Ray, Precision Oncology News, August 29, 2022 (Posted: Aug 30, 2022 9AM)

Current screening guidelines recommend that patients between ages 45 and 75 and at average risk for colon cancer, should have colonoscopies every 10 years. However, patients with a personal or family history of colorectal cancer or colon polyps, or patients with Lynch or another inherited cancer syndrome associated with heightened colon cancer risk, may be eligible for more frequent screenings.

Bowel cancer: what role do our genes play?
Genetics Education Program, August 19, 2022 (Posted: Aug 21, 2022 3PM)

A person’s risk of developing colorectal cancer is influenced by lifestyle factors, such as a low-fiber diet and lack of regular physical activity; however, as is the case with breast cancer, some inherited genetic variants increase the likelihood of a person developing colorectal cancer. In this article, we look at two genetically inherited syndromes and examine how and why they increase a person’s risk of this particular cancer.

Genomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer.
Chatila Walid K et al. Nature medicine 2022 8 (Posted: Aug 16, 2022 10AM)

To define correlates of response to neoadjuvant therapy, we analyzed genomic and transcriptomic profiles of 738 untreated rectal cancers. APC mutations were less frequent in the lower than in the middle and upper rectum, which could explain the more aggressive behavior of distal tumors. No somatic alterations had significant associations with response to neoadjuvant therapy in a treatment-agnostic manner, but KRAS mutations were associated with faster relapse in patients treated with neoadjuvant chemoradiation followed by consolidative chemotherapy. Overexpression of IGF2 and L1CAM was associated with decreased response to neoadjuvant therapy.

Circulating tumor DNA to guide rechallenge with panitumumab in metastatic colorectal cancer: the phase 2 CHRONOS trial.
Sartore-Bianchi Andrea et al. Nature medicine 2022 8 (Posted: Aug 03, 2022 6AM)

The primary endpoint of the trial was met; and, of 27 enrolled patients, eight (30%) achieved partial response and 17 (63%) disease control, including two unconfirmed responses. These clinical results favorably compare with standard third-line treatments and show that interventional liquid biopsies can be effectively and safely exploited in a timely manner to guide anti-EGFR rechallenge therapy with panitumumab in patients with mCRC.

Identification of two intrinsic epithelial subtypes of colorectal cancer.
et al. Nature genetics 2022 7 (Posted: Jul 10, 2022 2PM)

By integrating single-cell and bulk transcriptomic analyses, we found that malignant cells belong to two major intrinsic epithelial subtypes. We propose a refined, three-tiered classification of colorectal cancer subtypes based on intrinsic epithelial subtypes, microsatellite instability status and the presence of fibrosis.

A novel AI device for real-time optical characterization of colorectal polyps
C Biffi et al, NPJ Digital Medicine, June 30, 2022 (Posted: Jun 30, 2022 7AM)

Comprehensive profiling of 1015 patients’ exomes reveals genomic-clinical associations in colorectal cancer
Q Zhao et al, Nature Comms, April 29, 2022 (Posted: Apr 29, 2022 0PM)

The genetic basis of colorectal cancer (CRC) and its clinical associations remain poorly understood due to limited samples or targeted genes in current studies. Here, we perform ultradeep whole-exome sequencing on 1015 patients with CRC as part of the ChangKang Project. We identify 46 high-confident significantly mutated genes, 8 of which mutate in 14.9% of patients: LYST, DAPK1, CR2, KIF16B, NPIPB15, SYTL2, ZNF91, and KIAA0586. With an unsupervised clustering algorithm, we propose a subtyping strategy that classisfies CRC patients into four genomic subtypes with distinct clinical characteristics.

Lynch syndrome; towards more personalized management?
J Llach et al, Best Practice & Research Clinical Gastroenterology, March 2022 (Posted: Apr 20, 2022 9AM)

Lynch syndrome is the most common inherited cause of colorectal (lifetime risk up to 70%) and endometrial cancer. The diagnosis of Lynch syndrome facilitates preventive measures aimed at reducing the incidence and mortality of cancer. Colonoscopic surveillance for colorectal cancer, aspirin, and prophylactic hysterectomy and bilateral salpo-oopherectomy for endometrial and/or ovarian cancer have demonstrated to effectively reduce cancer mortality in this population. However, the lifetime risk of each cancer in people with Lynch syndrome is gene-specific and may be modified by environmental factors. Furthermore, the benefits of surveillance strategies need to be balanced against the risk of over-diagnosis and be supported by evidence of improved outcomes

Opportunities for personalizing colorectal cancer care: an analysis of SEER-medicare data
ZT Rivers et al, The PGX journal March 31, 2022 (Posted: Apr 02, 2022 8AM)

We analyzed real-world treatment using a cancer registry and claims dataset to explore pharmacogenomic (PGx) medication treatment patterns and characterize exposure. In a cohort of 6957 patients, most (86.9%) were exposed to at least one chemotherapy medication with PGx guidelines. In a cohort of 2223 patients with retail pharmacy claims available, most (79.2%) were treated with at least one non-chemotherapy (79.2%) medication with PGx guidelines. PGx-associated chemotherapy exposure was associated with age, race/ethnicity, educational attainment, and rurality. PGx-associated non-chemotherapy exposure was associated with medication use and comorbidities.

Effect of Patient-Directed Messaging on Colorectal Cancer Screening A Randomized Clinical Trial
A Oyalowo et al, JAMA Network Open, March 31, 2022 (Posted: Apr 01, 2022 1PM)

Are individuals more likely to complete colorectal cancer screening if they receive communication that is tailored to their attitudes and beliefs? In this randomized clinical trial including 600 participants, a tailored message intervention and a generic message intervention were significantly more effective at increasing colonoscopy scheduling and colonoscopy completion rates compared with usual care. The tailored message intervention was not shown to be superior to the generic message intervention.

Evaluation of Comparative Surveillance Strategies of Circulating Tumor DNA, Imaging, and Carcinoembryonic Antigen Levels in Patients With Resected Colorectal Cancer
M Fakih et al, JAMA Network Open (Posted: Mar 09, 2022 11AM)

s serial analysis of circulating tumor DNA (ctDNA) associated with improved sensitivity and earlier detection of recurrence compared with standard imaging and evaluation of carcinoembryonic antigen (CEA) levels per National Comprehensive Cancer Network guidelines in patients with resected colorectal cancer? In this cohort study of 48 patients with resected colorectal cancer, 15 had confirmed disease recurrence by imaging, of whom only 8 had a concurrent positive ctDNA finding. The combination of imaging and CEA measurement had better sensitivity compared with ctDNA in identifying disease recurrence (73.3% vs 53.3%).

Index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes
M Abedalthagafi, EJHG, January 22, 2022 (Posted: Jan 24, 2022 2PM)

Identification of a cancer pathogenic variant variant in an index-case facilitates management strategies such as decisions around the extent of surgical management or targeted therapeutic strategies. It also defines the cancer prevention and early detection strategies in at-risk family members. Cascade screening also reassures non-carrier relatives, excluding them from intensive surveillance and at the same time, contributing to the cost-effectiveness of genetic testing for a wider population.

30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes
ER Woodward et al, EJHG, December 6, 2021 (Posted: Dec 06, 2021 6AM)

We recorded 2082 positive index case diagnostic screening tests, generating 3216 positive and 3140 negative family cascade (non-index) tests. This is equivalent to an average of 3.05 subsequent cascade tests per positive diagnostic index test, with 1.54 positive and 1.51 negative non-index tests per family. The CPGs with the highest numbers of non-index positive cases identified on cascade testing were BRCA1/2 (n?=?1999) and the mismatch repair CPGs associated with Lynch Syndrome (n?=?731).

Identifying Diagnostic MicroRNAs and Investigating Their Biological Implications in Rectal Cancer
JK Kim et al, JAMA Network Open, December 4, 2021 (Posted: Dec 05, 2021 3PM)

This diagnostic study of 2 independent cohorts found that a set of 19 miRNAs can effectively distinguish locally advanced disease (stage II or III) among nonmetastatic rectal cancers. Within this set of miRNAs, 3 miRNA-mRNA functional interactions were identified by integrative transcriptome analysis.

Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial
Y Nakamura et al, Nature Medicine, November 11, 2021 (Posted: Nov 11, 2021 0PM)

Racial and Ethnic Disparities Among Participants in Precision Oncology Clinical Studies
CM Aldriguetti et al, JAMA Network Open, November 8, 2021 (Posted: Nov 09, 2021 6AM)

This cross-sectional analysis evaluates breast, prostate, lung, and colorectal cancer studies in the registry with precision medicine objectives and reporting race and ethnicity—a total of 93 studies with 5867 total enrollees. An underrepresentation of minority racial groups and an overrepresentation of non-Hispanic White participants relative to their incidence in the US cancer population was found in precision oncology studies.

KRAS and BRAF Mutations in Stage II/III Colon Cancer: A Systematic Review and Meta-Analysis.
Formica Vincenzo et al. Journal of the National Cancer Institute 2021 9 (Posted: Sep 22, 2021 9AM)

This is a meta-analysis of adjuvant phase III trials in patients with stage II and III colon cancer with available data on the impact of KRAS/BRAF mutations on both disease-free survival (DFS) and overall survival (OS). Both KRAS and BRAF mutations were statistically significantly associated with both DFS and OS, with the mutation effect being enhanced by MSI adjustment. Effective adjuvant treatment for microsatellite stable BRAF or KRAS-mutated colon cancer represents an unmet clinical need.

Importance of Family History of Colorectal Cancer In Situ Versus Invasive Colorectal Cancer: A Nationwide Cohort Study.
Tian Yu et al. Journal of the National Comprehensive Cancer Network : JNCCN 2021 1-6 (Posted: Sep 17, 2021 6AM)

Clinical Response to Immunotherapy Targeting Programmed Cell Death Receptor 1/Programmed Cell Death Ligand 1 in Patients With Treatment-Resistant Microsatellite Stable Colorectal Cancer With and Without Liver Metastases
C Wang et al, JAMA Network Open, August 9, 2021 (Posted: Aug 10, 2021 10AM)

Pattern of DNA Damage Links Colorectal Cancer and Diet High in Red Meat
NCI, June 2021 Brand (Posted: Aug 02, 2021 4PM)

The discovery of alkylating mutational signature associated with the consumption of red and processed meats “further implicates” diet in the development of colorectal cancer". To arrive at their findings, the research team analyzed tumor DNA from hundreds of people with colorectal cancer who had provided in-depth information about what they ate in the years before they were diagnosed with the disease.

Vaccine to Prevent Hereditary Cancers Nears Human Trials
S Jenks, NCI Blog, July 2021 Brand (Posted: Jul 18, 2021 7AM)

One of the first-ever vaccines for the prevention of colorectal and other cancers in patients at high genetic risk for these malignancies is expected to start its early phase safety and immunogenicity trial in the first quarter of 2022, according to investigators. Although still in the design phase, the study will test a neoantigen-based vaccine against Lynch syndrome, a common hereditary condition that carries a 70-80% lifetime risk for colorectal cancer. The syndrome also raises the risk for developing endometrial cancer and several other cancers, often before age 50 years.

Prospective Statewide Study of Universal Screening for Hereditary Colorectal Cancer: The Ohio Colorectal Cancer Prevention Initiative.
Pearlman Rachel et al. JCO precision oncology 2021 7 (Posted: Jul 14, 2021 6AM)

Three thousand three hundred ten unselected adults who underwent surgical resection for primary invasive CRC were prospectively accrued from 51 hospitals across Ohio between January 1, 2013, and December 31, 2016. Universal Tumor screening (UTS) for mismatch repair (MMR) deficiency was performed for all. UTS alone is insufficient for identifying a large proportion of CRC patients with hereditary syndromes, including some with LS. At a minimum, 7.1% of individuals with CRC have a PGV and pan-cancer MGPT should be considered for all patients with CRC.

Expanding Germline Testing to All Patients With Esophagogastric Cancers—Easy to Do, Harder to Justify
JAMA Network Open, July 12, 2021 (Posted: Jul 13, 2021 7AM)

Guidelines currently support disease site–specific testing of patients with colorectal cancer younger than 50 years and all patients with pancreatic cancer. Testing patients with esophagogastric cancer (EGC), however, currently requires a known familial variant or a strong personal or family history indicative of a hereditary cancer syndrome, such as hereditary diffuse gastric cancer or Lynch syndrome.

MFHP Cancer
CDC, July 2021 (Posted: Jul 11, 2021 2PM)

Use the app to collect your family history of cancer and determine your risk for breast, ovarian and/or colorectal cancer. You can view your risk factors and learn about what to do next. You will also be able to see your family's history of cancer in a family tree.

Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.
et al. JAMA surgery 2021 7 (Posted: Jul 01, 2021 7AM)

Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown

Genetic testing for inherited colorectal cancer and polyposis, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)
R Mao et al, Genetics in Medicine, June 17, 2021 (Posted: Jun 18, 2021 6AM)

Given the overlapping phenotypes of the cancer syndromes along with the limited sensitivity of using clinical criteria alone, a multigene panel testing approach to diagnose these conditions using next-generation sequencing (NGS) is effective and efficient.

Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study
The International Mismatch Repair Consortium, The Lancet Oncology, June 7, 2021 (Posted: Jun 09, 2021 7AM)

Familial risk factors result in a wide within-gene variation in the risk of colorectal cancer for men and women from each continent who all carried pathogenic variants in the same gene or the MSH2 c.942+3A>T variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7–56% of carriers having a colorectal cancer penetrance of less than 20%, 9–44% having a penetrance of more than 80%, and only 10–19% having a penetrance of 40–60%.

Clinical Value of Consensus Molecular Subtypes in Colorectal Cancer: A Systematic Review and Meta-Analysis
ST Hoorn et al, JNCI, June 2021 (Posted: Jun 07, 2021 8AM)

The consensus molecular subtypes (CMSs) of colorectal cancer (CRC) capture tumor heterogeneity at the gene-expression level. Currently, a restricted number of molecular features are used to guide treatment for CRC. We summarize the evidence on the clinical value of the CMSs.

Identification of microbial markers across populations in early detection of colorectal cancer
Y Wu et al, Nat Comms, May 24, 2021 (Posted: May 25, 2021 7AM)

Associations between gut microbiota and colorectal cancer (CRC) have been widely investigated. However, the replicable markers for early-stage adenoma diagnosis across multiple populations remain elusive. Here, we perform an integrated analysis on 1056 public fecal samples, to identify adenoma-associated microbial markers for early detection of CRC.

Risk of colorectal cancer in first degree relatives of patients with colorectal polyps: nationwide case-control study in Sweden
M Song et al, BMJ May 2021 (Posted: May 05, 2021 7AM)

After adjusting for family history of CRC, the siblings and children of patients with colorectal polyps are still at higher risk of CRC, particularly early onset CRC. Early screening for CRC might be considered for first degree relatives of patients with polyps.

Interpretable survival prediction for colorectal cancer using deep learning
E Wulczyn et al, NPJ Digital Medicine, April 19, 2021 (Posted: Apr 19, 2021 9AM)

Deriving interpretable prognostic features from deep-learning-based prognostic histopathology models remains a challenge. We developed a deep learning system for predicting survival for stage II and III colorectal cancer using 3652 cases. When evaluated on two validation datasets containing 1239 cases and 738 cases, respectively, the DLS achieved a 5-year disease-specific survival AUC of 0.70 and 0.69 and added significant predictive value to a set of nine clinicopathologic features.

Effectiveness of patient-targeted interventions to inform decision making and improve uptake of colorectal cancer genetic evaluation for at-risk individuals: A systematic review.
Li Huanhuan et al. International journal of nursing studies 2021 118103928 (Posted: Apr 16, 2021 10AM)

Based on this review, the conclusion cannot be made that interventions for risk assessment, education, and decision aids have positive effects on the uptake of colorectal cancer genetic evaluation for at-risk individuals and their informed decision making. Future studies with rigorous designs are recommended

Stool-based Colorectal Cancer Screening in the COVID-19 Era
WD Dotson et al, CDC Blog, April, 12, 2021 Brand (Posted: Apr 13, 2021 7AM)

The broad aftermath of the pandemic will be with us for many years to come. Some of the resulting changes can be positive, including an increased awareness of digital, genomic and other precision health technologies which may provide alternatives to traditional screening methods.

A Proclamation on National Colorectal Cancer Awareness Month, 2021
The White House, March 1, 2021 (Posted: Mar 03, 2021 7AM)

People with increased risk for developing the disease include certain racial and ethnic minority populations, as well as individuals with inflammatory bowel disease, a family history of colorectal cancer, or other risk factors such as tobacco use.

High expression of ACE2 and TMPRSS2 and clinical characteristics of COVID-19 in colorectal cancer patients
C Liu et al, NPJ Genomic Medicine, January 21, 2021 (Posted: Jan 22, 2021 9AM)

Pandemic Spotlights In-home Colon Cancer Screening Tests
MC Jaclevic, JAMA, December 23, 2020 (Posted: Dec 24, 2020 7AM)

Long overshadowed by colonoscopy, stool-based screening tests that patients perform at home are getting a boost as hospitals halted and then curtailed nonemergency procedures in an effort to preserve resources and prevent novel coronavirus transmission. One type of test, multitarget stool DNA detects cancer biomarkers and blood in the stools.

Pembrolizumab in Microsatellite-Instability–High Advanced Colorectal Cancer
T Andre et al, NEJM, December 2, 2020 (Posted: Dec 03, 2020 7AM)

In this phase 3, open-label trial, 307 patients with metastatic MSI-H–dMMR colorectal cancer who had not previously received treatment, Pembrolizumab led to significantly longer progression-free survival than chemotherapy when received as first-line therapy for MSI-H–dMMR metastatic colorectal cancer, with fewer treatment-related adverse events

Pembrolizumab in MSI-H–dMMR Advanced Colorectal Cancer — A New Standard of Care
A Grothey, NEJM, December 2, 2020 (Posted: Dec 03, 2020 7AM)

Germline mutations in genes encoding mismatch repair proteins are hallmarks of Lynch syndrome, but the deficient mismatch repair (dMMR) phenotype is commonly found in sporadic, nonfamilial cancers. The phenotype itself leads to a high degree of microsatellite instability (MSI-H), which is assessed with the use of polymerase chain reaction or next-generation sequencing. MSI-H–dMMR cancers have been recognized to be sensitive to treatment with immune checkpoint inhibitors.

Rising incidence of early-onset colorectal cancer - a call to action.
Akimoto Naohiko et al. Nature reviews. Clinical oncology 2020 Nov (Posted: Nov 24, 2020 8AM)

The reasons for this increase remain unknown but plausible hypotheses include greater exposure to potential risk factors, such as a Western-style diet, obesity, physical inactivity and antibiotic use, especially during the early prenatal to adolescent periods of life. These exposures can not only cause genetic and epigenetic alterations in colorectal epithelial cells but also affect the gut microbiota and host immunity.

Association of mismatch repair status with survival and response to neoadjuvant chemo(radio)therapy in rectal cancer
SB Ye, NPJ Precision Oncology, September 8, 2020 (Posted: Sep 09, 2020 9AM)

Prior reports have indicated that defective mismatch repair (MMR) has a favorable impact on outcome in colorectal cancer patients treated with surgery, immunotherapy, or adjuvant chemotherapy. Here we report that dMMR was associated with improved disease-free survival (DFS) (P?=?0.034) in patients receiving neoadjuvant chemotherapy (NCT).

Effect of a Digital Health Intervention on Decreasing Barriers and Increasing Facilitators for Colorectal Cancer Screening in Vulnerable Patients
NMD Thompson et al, CEBP, August 2020 (Posted: Sep 01, 2020 8AM)

A patient decision aid called Mobile Patient Technology for Health-CRC (mPATH-CRC) doubled the proportion of patients who completed colorectal cancer screening. IT increased completion of colorectal cancer screening by affecting patient-level and system-level mediators. The most powerful mediator was the occurrence of a patient–provider discussion about screening.

Genetic Disease Risk Impacted by Entire Genome, Study Reveals
J Kent, Health Analytics, August 27, 2020 (Posted: Aug 28, 2020 8AM)

In people with a single-gene variant that contributes to high genetic disease risk – specifically for heart disease, breast cancer, or colorectal cancer – the rest of the genome can alter that risk. Some individuals are genetically predisposed to disease, but these disease predictions aren’t always accurate.

Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.
Thomas Minta et al. American journal of human genetics 2020 Jul (Posted: Aug 09, 2020 0PM)

We are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. 90% of these individuals have no family history and would have been considered average risk under current screening guidelines.

A Genomic Test for Colorectal Cancer Risk: Is This Acceptable and Feasible in Primary Care?
S Saya et al, Public Health Genomics, July 2020 (Posted: Jul 21, 2020 7AM)

We aimed to assess the feasibility and acceptability of administering a CRC genomic test in primary care. In 150 participants, test uptake was high (126, 84%), with 125 (83%) having good knowledge of the genomic test. Moderate risk participants were impacted more by the test.

ctDNA applications and integration in colorectal cancer: an NCI Colon and Rectal–Anal Task Forces whitepaper
A Dasari et al, Nature Rev Clin Oncol, July 6, 2020 (Posted: Jul 07, 2020 10AM)

The panel focused on four key areas in which ctDNA has the potential to change clinical practice, including the detection of minimal residual disease, the management of patients with rectal cancer, monitoring responses to therapy, and tracking clonal dynamics in response to targeted therapies and other systemic treatments.

Clinical, Pathology, Genetic, and Molecular Features of Colorectal Tumors in Adolescents and Adults 25 Years or Younger.
de Voer Richarda M et al. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2020 Jun (Posted: Jun 28, 2020 3PM)

We found features of CRCs in adolescents or young adults to differ from those of patients older than 60 years. In 39% of patients a genetic tumor-risk syndrome was identified. This suggests new strategies for clinical management. Performing genetic analyses for every individual diagnosed with CRC at age 25 years or younger would aid in this optimization.

Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial
J Burn et al, The Lancet June 13, 2020 (Posted: Jun 13, 2020 7AM)

In the double-blind, randomized CAPP2 trial, 861 patients from 43 international centres worldwide (707 [82%] from Europe, 112 [13%] from Australasia, 38 [4%] from Africa, and four [<1%] from The Americas) with Lynch syndrome were randomly assigned to receive 600 mg aspirin daily or placebo. Cancer outcomes were monitored for at least 10 years from recruitment.

Local cellular cues that influence the immunology of colorectal cancer treatment
GP Donaldson et al, Nature Medicine, May 25, 2020 (Posted: May 26, 2020 7AM)

Therapeutic interventions in colorectal cancer are dependent on immune responses to dying epithelial cells that are modulated by specific members of the gut microbiota.

Efficacy of Immunotherapy in Microsatellite-Stable or Mismatch Repair Proficient Colorectal Cancer—Fact or Fiction?
RB Corcoran et al, JAMA Oncology, May 7, 2020 (Posted: May 08, 2020 9AM)

The observation that a subset of patients with MSS colorectal cancer may derive some modest benefit from combined immune checkpoint blockade suggests that novel combinations of immune checkpoint inhibitors with agents that may further enhance the immune response may be a promising approach, and several clinical trials are ongoing.

NCCN Updates Clinical Practice Guideline for Colorectal Cancer
JCCN, May 1, 2020 (Posted: May 02, 2020 8AM)

Potential impact of family history–based screening guidelines on the detection of early‚Äźonset colorectal cancer
S Gupta et al, Cancer, April 20, 2020 (Posted: Apr 20, 2020 7AM)

Of Colorectal cancer cases aged 40 to 49 years, 1 in 4 met family history–based early screening criteria, and nearly all cases who met these criteria could have had CRC diagnosed earlier (or possibly even prevented) if earlier screening had been implemented as per family history–based guidelines.

New study highlights importance of family history-based screening for colorectal cancer
H Zia, Stat News, April 20, 2020 (Posted: Apr 20, 2020 7AM)

Associations Between Mutations in MSH6 and PMS2 and Risk of Surveillance-detected Colorectal Cancer.
Lamba Mehul et al. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2020 Mar (Posted: Apr 08, 2020 9AM)

Cost-effectiveness Evaluation of Targeted Surgical and Endoscopic Therapies for Early Colorectal Adenocarcinoma Based on Biomarker Profiles
SR Jang et al. JAMA Network Open, March 9, 2020 (Posted: Mar 10, 2020 8AM)

Assessment of Treatment Cost-effectiveness Using a Colorectal Cancer Mutation Profile
TJ Yeatman et al, JAMA Netwotk Open, March 9, 2020 (Posted: Mar 10, 2020 8AM)

The addition of genetic testing to clinicopathologic features (ie, the current standard of care) may provide a new means of determining the most cost-effective, highest-quality approach for this early stage of disease. A prospective comparison of genetic vs pathologic staging in predicting surgical pathologic staging will be necessary.

What Is Colorectal Cancer Screening?
CDC, March 2020 Brand (Posted: Mar 09, 2020 8AM)

Regular screening, beginning at age 50, is the key to preventing colorectal cancer. If you think you may be at increased risk for colorectal cancer, learn your family health history and ask your doctor if you should begin screening before age 50.

Should polygenic risk scores be used in risk-stratified colorectal cancer screening?
WD Dotson et al, CDC Blog Post, February 24, 2020 Brand (Posted: Feb 25, 2020 9AM)

Dcreening based on polygenic risk prediction is not ready for widespread implementation. Stratification based on polygenic and/or multifactorial risk assessment may mature to the point of displacing family history-based approaches, but for the foreseeable future, family history may remain a valuable clinical tool for identifying individuals at increased risk.

Deep learning for prediction of colorectal cancer outcome: a discovery and validation study.
Skrede Ole-Johan et al. Lancet (London, England) 2020 Feb (10221) 350-360 (Posted: Feb 03, 2020 9AM)

A clinically useful prognostic marker was developed using deep learning allied to digital scanning of conventional haematoxylin and eosin stained tumor tissue sections. The biomarker stratified stage II and III patients into sufficiently distinct prognostic groups that potentially could be used to guide treatment selection.

Gut Microbiome Link to Increased CRC in Younger Adults?
R Nelson, Medscape, January 27, 2020 (Posted: Feb 02, 2020 9AM)

Colorectal cancer (CRC) has increased dramatically in adults younger than 50 years of age in many high-income countries, and there has been speculation as to why. Now, a small study points to differences in the gut microbiome between younger and older CRC patients.

A new comprehensive colorectal cancer risk prediction model incorporating family history, personal characteristics, and environmental factors.
Zheng Yingye et al. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2020 Jan (Posted: Jan 16, 2020 8AM)

A familial risk profile (FRP) was calculated to summarize individuals' risk based on detailed cancer family history, family structure, probabilities of mutation in major CRC susceptibility genes, and a polygenic component.Our findings suggested detailed family history may be useful for targeted risk-based screening and clinical management


Disclaimer: Articles listed in Hot Topics of the Day are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.