High-throughput sequencing and in-silico analysis confirm pathogenicity of novel MSH3 variants in African American colorectal cancer.

The maintenance of DNA sequence integrity is critical to avoid accumulation of cancer-causing mutations. Inactivation of DNA Mismatch Repair (MMR) genes (e.g., MLH1 and MSH2) is common among many cancers, including colorectal cancer (CRC) and is the driver of classic microsatellite instability (MSI) in tumors. Somatic MSH3 alterations have been linked to a specific form of MSI called elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) that is associated with patient poor prognosis and elevated among African American (AA) rectal cancer patients. Genetic variants of MSH3 and their pathogenicity vary among different populations, such as among AA, which are not well-represented in publicly available databases. Targeted exome sequencing of MSH3 among AA CRC samples followed by computational bioinformatic pipeline and molecular dynamic simulation analysis approach confirmed six identified MSH3 variants (c.G1237A, c.C2759T, c.G1397A, c.G2926A, c.C3028T, c.G3241A) that corresponded to MSH3 amino-acid changes (p.E413K; p.S466N; p.S920F; p.E976K; p.H1010Y; p.E1081K). All identified MSH3 variants were non-synonymous, novel, pathogenic, and show loss or gain of hydrogen bonding, ionic bonding, hydrophobic bonding, and disulfide bonding and have a deleterious effect on the structure of MSH3 protein. Some variants were located within the ATPase site of MSH3, affecting ATP hydrolysis that is critical for MSH3's function. Other variants were in the MSH3-MSH2 interacting domain, important for MSH3's binding to MSH2. Overall, our data suggest that these variants among AA CRC patients affect the function of MSH3 making them pathogenic and likely contributing to the development or advancement of CRC among AA. Further clarifying functional studies will be necessary to fully understand the impact of these variants on MSH3 function and CRC development in AA patients.

Up-to-Date Colonoscopy Use in Asian and Hispanic Subgroups in New York City, 2003-2016.

BACKGROUND: Colorectal cancer screening uptake in the United States overall has increased, but racial/ethnic disparities persist and data on colonoscopy uptake by racial/ethnic subgroups are lacking. We sought to better characterize these trends and to identify predictors of colonoscopy uptake, particularly among Asian and Hispanic subgroups. STUDY: We used data from the New York City Community Health Survey to generate estimates of up-to-date colonoscopy use in Asian and Hispanic subgroups across 6 time periods spanning 2003-2016. For each subgroup, we calculated the percent change in colonoscopy uptake over the study period and the difference in uptake compared to non-Hispanic Whites in 2015-2016. We also used multivariable logistic regression to identify predictors of colonoscopy uptake. RESULTS: All racial and ethnic subgroups with reliable estimates saw a net increase in colonoscopy uptake between 2003 and 2016. In 2015-2016, compared with non-Hispanic Whites, Puerto Ricans, Dominicans, and Central/South Americans had higher colonoscopy uptake, whereas Chinese, Asian Indians, and Mexicans had lower uptake. On multivariable analysis, age, marital status, insurance status, primary care provider, receipt of flu vaccine, frequency of exercise, and smoking status were the most consistent predictors of colonoscopy uptake (≥4 time periods). CONCLUSIONS: We found significant variation in colonoscopy uptake among Asian and Hispanic subgroups. We also identified numerous demographic, socioeconomic, and health-related predictors of colonoscopy uptake. These findings highlight the importance of examining health disparities through the lens of disaggregated racial/ethnic subgroups and have the potential to inform future public health interventions.

Mi-CARE: Comparing Three Evidence-Based Interventions to Promote Colorectal Cancer Screening among Ethnic Minorities within Three Different Clinical Contexts.

Multiple evidence-based interventions (EBIs) have been developed to improve the completion of colorectal cancer (CRC) screening within Federally Qualified Health Centers (FQHCs) and other safety net settings in marginalized communities. Little effort has been made, however, to evaluate their relative effectiveness across different clinical contexts and populations. To this end, we tested the relative effectiveness of three EBIs (mailed birthday cards, lay navigation, and provider-delivered education) among a convenience sample of 1252 patients (aged 50-75 years old, who were due for CRC screening and scheduled for a visit at one of three clinics within a network of Federally Qualified Health Centers (FQHCs) in the United States. To be eligible for the study, patients had to identify as African American (AA) or Latino American (LA). We compared the effects of the three EBIs on CRC screening completion using logistic regression. Overall, 20% of the study population, an increase from a baseline of 13%, completed CRC screening. Clinical demographics appeared to influence the effectiveness of the EBIs. Mailed birthday reminders appeared to be the most effective within the multi-ethnic clinic (p = 0.03), provider-delivered education within the predominantly LA clinic (p = 0.02), and lay navigation within the predominantly AA clinic (p = 0.03). These findings highlight the importance of understanding clinical context when selecting which evidence-based interventions to deploy.

Colorectal cancer disparities in Latin America: Mortality trends 1990-2019 and a paradox association with human development.

BACKGROUND: Colorectal cancer mortality is growing in Latin America. It is known for a marked income disparity between its countries, and there is a consistent association with development. Our purpose was to describe trends in colorectal cancer mortality in Latin America between 1990 and 2019, identifying differences by human development categories. METHODS: We extracted age-adjusted mortality rate from the Global Burden of Disease (GBD) Study from 22 Latin American countries, subregions, and country groups previously ranked by the GBD study due to Sociodemographic Index (SDI) between 1990 and 2019. We applied the segmented regression model to analyze the time trend. Also, we estimated the correlation between mortality rates and Human Development Index (HDI) categories for countries. RESULTS: Between 1990 and 2019, colorectal cancer adjusted mortality rate increased by 20.56% in Latin America (95% CI 19.75% - 21.25%). Between 1990 and 2004, the average annual percentage change (APC) was 0.11% per year (95% CI 0.10-0.12), and between 2004 and 2019 there was a deceleration (APC = 0.04% per year, 95% CI 0.03%- 0.05%). There is great heterogeneity among the countries of the region. Correlation between these two variables was 0.52 for 1990 and 2019. When separated into HDI groups, the correlation varied in the direction of the association and its magnitude, typifying an effect modification known as Simpson's Paradox. CONCLUSIONS: Human development factors may be important for assessing variation in cancer mortality on a global scale. Studies that assess the social and -economic contexts of countries are necessary for robust evaluation and provision of preventive, diagnostic and curative services to reduce cancer mortality in Latin America.

Who, where, when: Colorectal cancer disparities by race and ethnicity, subsite, and stage.

BACKGROUND: There are well-established disparities in colorectal cancer (CRC) outcomes between White and Black patients; however, assessments of CRC disparities for other racial/ethnic groups are limited. METHODS: The Surveillance, Epidemiology, and End Results database identified patients aged 50-74 years with CRC adenocarcinoma from 2000 to 2019. Trends in age-adjusted incidence rates were computed by stage at diagnosis and subsite across five broad race/ethnic groups (White, Black, Asian/Pacific Islander [API], American Indian/Alaskan Native [AIAN], and Hispanic) and four API subgroups (East Asian, Southeast Asian, South Asian, and Pacific Islander) Multivariable logistic regression evaluated associations between race/ethnicity and diagnosis stage. Multivariable Cox proportional hazards models assessed differences in cause-specific survival (CSS). RESULTS: Hispanic, AIAN, Southeast Asian, Pacific Islander, and Black patients were 3% to 28% more likely than Whites to be diagnosed with distant stage CRC, whereas East Asian and South Asians had similar or lower risk of distant stage CRC. From Cox regression analysis, Black, AIAN, and Pacific Islanders also experienced worse CSS, while East Asian and South Asian patient groups experienced better CSS. No significant differences in CSS were observed among Hispanic, Southeast Asian, and White patients. When stratified by stage, Black patients had worse CSS across all stages (early, hazard ratio (HR) = 1.38; regional, HR = 1.22; distant, HR: 1.07, p < 0.05 for all). CONCLUSION: Despite advances in CRC screening, treatment and early detection efforts, marked racial/ethnic disparities in incidence, stage at diagnosis, and survival persist. Findings demonstrate the extent to which aggregating heterogenous populations masks significant variability in CRC outcomes within race/ethnic subgroups.

Survival of Middle Eastern and North African Individuals Diagnosed with Colorectal Cancer: A Population-Based Study in California.

BACKGROUND: Literature on colorectal cancer outcomes in individuals of Middle Eastern and North African (MENA) descent is limited. To address this gap, we estimated five-year colorectal cancer-specific survival by race and ethnicity, including MENA individuals, in a diverse, population-based sample in California. METHODS: We identified adults (ages 18-79 years) diagnosed with a first or only colorectal cancer in 2004 to 2017 using the California Cancer Registry (CCR), including non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, Hispanic, and MENA individuals. For each racial/ethnic group, we calculated five-year colorectal cancer-specific survival and used Cox proportional hazards regression models to examine the association of race/ethnicity and survival, adjusting for clinical and socio demographic factors. RESULTS: Of 110,192 persons diagnosed with colorectal cancer, five-year colorectal cancer-specific survival was lowest in Black (61.0%) and highest in MENA (73.2%) individuals. Asian (72.2%) individuals had higher survival than White (70.0%) and Hispanic (68.2%) individuals. In adjusted analysis, MENA [adjusted HR (aHR), 0.82; 95% confidence interval (CI), 0.76-0.89], Asian (aHR, 0.86; 95% CI, 0.83-0.90), and Hispanic (aHR, 0.94; 95% CI, 0.91-0.97) race/ethnicity were associated with higher, and Black (aHR, 1.13; 95% CI, 1.09-1.18) race/ethnicity was associated with lower survival compared with non-Hispanic White race/ethnicity. CONCLUSIONS: To our knowledge, this is the first study to report colorectal cancer survival in MENA individuals in the United States. We observed higher survival of MENA individuals compared with other racial/ethnic groups, adjusting for sociodemographic and clinical factors. IMPACT: Future studies are needed to identify factors contributing to cancer outcomes in this unique population.

A common cancer at an uncommon age.

The etiology of early-onset colorectal cancer needs to be understood to tackle rising incidence.

Elevated colorectal cancer incidence among American Indian/Alaska Native persons in Alaska compared to other populations worldwide.

Colorectal cancer (CRC) is a leading cancer worldwide; incidence varies greatly by country and racial group. We compared 2018 American Indian/Alaska Native (AI/AN) CRC incidence rates in Alaska to other Tribal, racial, and international population rates. AI/AN persons in Alaska had the highest CRC incidence rate among US Tribal and racial groups (61.9/100,000 in 2018). AI/AN persons in Alaska also had higher rates than those reported for any other country in the world in 2018 except for Hungary, where males had a higher CRC incidence rate than AI/AN males in Alaska (70.6/100,000 and 63.6/100,000 respectively). This review of CRC incidence rates from populations in the United States and worldwide showed that AI/AN persons in Alaska had the highest documented incidence rate of CRC in the world in 2018. It is important to inform health systems serving AI/AN persons in Alaska about policies and interventions that can support CRC screening to reduce the burden of this disease.

The Intersection of Race and Rurality and its Effect on Colorectal Cancer Survival.

INTRODUCTION: Outcomes in colorectal cancer treatment are historically worse in Black people and residents of rural areas. Purported reasons include factors such as systemic racism, poverty, lack of access to care, and social determinants of health. We sought to determine whether outcomes worsened when race and rural residence intersected. METHODS: The National Cancer Database was queried for individuals with stage II-III colorectal cancer (2004-2018). To examine the intersectionality of race/rurality on outcomes, race (Black/White) and rurality (based on county) were combined into a single variable. Main outcome of interest was 5-year survival. Cox hazard regression analysis was performed to determine variables independently associating with survival. Control variables included age at diagnosis, sex, race, Charlson-Deyo score, insurance status, stage, and facility type. RESULTS: Of 463 948 patients, 5717 were Black-Rural, 50 742 were Black-Urban, 72 241 were White-Rural, and 33 5271 were White-Urban. Five-year mortality rate was 31.6%. Univariate Kaplan-Meier survival analysis demonstrated race-rurality was associated with overall survival (P < .001), with White-Urban having the greatest mean survival length (47.9 months) and Black-Rural with the lowest (46.7 months). Multivariable analysis found that Black-Rural (1.26, 95% confidence interval [1.20-1.32]), Black-Urban (1.16, [1.16-1.18]), and White-Rural (HR: 1.05; (1.04-1.07) had increased mortality when compared to White-Urban individuals (P < .001). CONCLUSION: Although White-Rural individuals fared worse than White-Urban, Black individuals fared worst of all, with the poorest outcomes observed in Black individuals in rural areas. This suggests that both Black race and rurality negatively affect survival, and act synergistically to further worsen outcomes.

Understanding the role of access in Hispanic cancer screening disparities.

BACKGROUND: Hispanic populations in the United States experience numerous barriers to care access. It is unclear how cancer screening disparities between Hispanic and non-Hispanic White individuals are explained by access to care, including having a usual source of care and health insurance coverage. METHODS: A secondary analysis of the 2019 National Health Interview Survey was conducted and included respondents who were sex- and age-eligible for cervical (n = 8316), breast (n = 6025), or colorectal cancer screening (n = 11,313). The proportion of ever screened and up to date for each screening type was compared.  Regression models evaluated whether controlling for reporting a usual source of care and type of health insurance (public, private, none) attenuated disparities between Hispanics and non-Hispanic White individuals. RESULTS: Hispanic individuals were less likely than non-Hispanic White individuals to be up to date with cervical cancer screening (71.6% vs. 74.6%) and colorectal cancer screening (52.9% vs. 70.3%), but up-to-date screening was similar for breast cancer (78.8% vs. 76.3%). Hispanic individuals (vs. non-Hispanic White) were less likely to have a usual source of care (77.9% vs. 86.0%) and more likely to be uninsured (23.6% vs. 7.1%). In regressions, insurance fully attenuated cervical cancer disparities. Controlling for both usual source of care and insurance type explained approximately half of the colorectal cancer screening disparities (adjusted risk difference: -8.3 [-11.2 to -4.8]). CONCLUSION: Addressing the high rate of uninsurance among Hispanic individuals could mitigate cancer screening disparities. Future research should build on the relative successes of breast cancer screening and investigate additional barriers for colorectal cancer screening. PLAIN LANGUAGE SUMMARY: This study uses data from a national survey to compare cancer screening use those who identify as Hispanic with those who identify as non-Hispanic White. Those who identify as Hispanic are much less likely to be up to date with colorectal cancer screening than those who identify as non-Hispanic White, slightly less likely to be up to date on cervical cancer screening, and similarly likely to receive breast cancer screening. Improving insurance coverage is important for health equity, as is further exploring what drives higher use of breast cancer screening and lower use of colorectal cancer screening.

Beliefs Underlying Colorectal Cancer Information Seeking Among Young Black Adults: a Reasoned Action Approach Elicitation Study.

Colorectal cancer in younger adults is more likely to be diagnosed at an advanced stage. Furthermore, younger Black adults are more likely to be diagnosed with and die from colorectal cancer than younger White adults. Given these persistent racial disparities, urgent attention is needed to increase colorectal cancer awareness and information seeking among young Black adults. Guided by the reasoned action approach, the purpose of this study was to identify behavioral, normative, and control beliefs that influence general colorectal cancer information seeking, talking to a healthcare provider about colorectal cancer, and talking to family about cancer history. The sample included N = 194 participants; Mage = 28.00 (SD = 5.48). Thirty-one percent had ever searched for colorectal cancer information. We identified salient educational advantages to seeking information about colorectal cancer and talking to healthcare providers and family members about cancer history. Barriers included fear, misinformation, low priority, inaccessibility of information, and lack of interest or willingness. This is one of the few studies to investigate cancer communication behaviors among young Black adults. The findings can inform interventions to motivate engagement in cancer communication behaviors.

Limited English Proficiency and Screening for Cervical, Breast, and Colorectal Cancers among Asian American Adults.

BACKGROUND: Literature shows that limited English proficiency (LEP) influences individual healthcare-seeking behaviors. The Asian population is the fastest-growing racial/ethnic group in the US, and approximately 50% of foreign-born Asians are estimated to live with LEP. OBJECTIVE: To examine associations of LEP and patient-provider language concordance (PPLC) with evidence-based cancer screening utilization for cervical, breast, and colorectal cancers among Asian American adults. METHODS: We obtained LEP, PPLC, and up-to-date status on the three types of cancer screening from a nationally representative sample of Asian Americans aged ≥ 18 years in the 2010-2016 and 2018 Medical Expenditure Panel Surveys. We used multivariable logistic regression models with recommended survey weighting to examine associations of LEP and PPLC with the cancer screening uptake based on USPSTF guidelines. RESULTS: The study population comprised 8953 respondents, representing 8.17 million Asian American adults. Overall, 11.9% of respondents experienced LEP; of those with LEP, 20% were with PPLC. In multivariable models, compared to respondents without LEP, respondents with LEP and without PPLC were significantly less likely to report up-to-date status on breast (OR = 0.44; 95% CI: 0.26-0.76), cervical (OR = 0.44; 95% CI: 0.26-0.75), or colorectal cancer screening (OR = 0.46; 95% CI: 0.26-0.80). However, these differences were not detected in respondents with LEP and with PPLC. CONCLUSION: LEP is associated with lower up-to-date status on cancer screening among Asian Americans, while PPLC seems to moderate this association. These findings suggest the enhancement for language-appropriate and culturally competent healthcare for Asian Americans with LEP, which helps accommodate their communication needs and promotes cancer screening.

The impact of race and socioeconomic status on stage IV colorectal cancer survival.

BACKGROUND: The aims of this study were to determine the impact of race and socioeconomics on survival in patients with stage IV colorectal cancer. METHODS: A prospective database of stage IV colorectal cancer patients treated at a multi-hospital health system from 2015 to 2019 was retrospectively analyzed. Univariate and multivariate survival analysis using log-rank Mantel-Cox test and Cox proportional hazard model were performed to determine the impact of race, socioeconomic factors, presentation, and treatment on overall survival. RESULTS: 4012 patients were diagnosed with colorectal cancer, of which 803 patients were stage IV. There were 677 (84.3%) White, and 108 (13.4%) Black patients. Black patients have worse 5-year overall survival than white patients (HR 1.43 (1.09-1.87)). Patients who received chemotherapy had significantly better survival than patients who did not receive chemotherapy (HR 0.58 (0.47-0.71)). Black patients have significantly lower rates of receiving chemotherapy as compared to white patients (61.1% vs 75.37%, p = 0.0018). CONCLUSION: Patients with Stage IV colorectal cancer have worse survival if they are black, older age, and did not receive chemotherapy.

A microRNA binding site polymorphism in the 3' UTR region of VEGF-A gene modifies colorectal cancer risk based on ethnicity: a meta-analysis.

BACKGROUND: Vascular endothelial growth factor A (VEGF-A) plays an integral role in angiogenesis by contributing to growth, development, and metastasis of solid tumors. Recently, a single-nucleotide polymorphism +936C/T located in the VEGF-A 3' untranslated region (UTR) facilitated the susceptibility of colorectal cancer. The association between VEGF-A gene polymorphism +936C/T and colorectal cancer risk has been widely studied in the last decade, but presently, the results furnished remain enigmatic. Hence, the study aimed to investigate the association between VEGF-A +936C/T miRNA binding site polymorphism and the risk of developing colorectal cancer. METHODS: This meta-analysis included 13 published case-control studies covering 3465 cases (colorectal cancer) and 3476 healthy controls. Publication bias was examined by means of Begg's funnel plots and Egger's regression tests. The quality of the studies included was evaluated using Newcastle-Ottawa scale. Subgroup analyses were performed in accordance to the various ethnicities of the study subjects and the study quality. RESULTS: From the data obtained, it is implied that VEGF-A +936C/T polymorphism did not correlate with elevated colorectal cancer risk in all genetic models. But the results acquired from the subgroup analysis in over dominant model (CT vs. CC + TT: OR = 1.5047, 95% CI = 1.19-1.90) suggest that VEGF-A +936C/T polymorphism leads to the raise in the risk of developing CRC among the East Asian population. No association was observed in Caucasian and South Asian population. CONCLUSIONS: Our results indicate that VEGF-A +936C/T polymorphism is not a risk factor for developing CRC in Caucasian and South Asian population. However, the East Asian population was related to an increased risk of developing colorectal cancer due to the presence of the minor allele.

Colorectal cancer community engagement: a qualitative exploration of American Indian voices from North Dakota.

BACKGROUND: American Indians (AI) in North Dakota present with higher rates of advanced-stage disease for screening detectable colorectal cancers and have lower overall baseline colorectal cancer screening rates than non-AIs. We sought to identify the perceived barriers and facilitators for the engagement with colorectal cancer prevention within North Dakota tribal communities. METHODS: Twelve semi-structured interviews were carried out across four tribal reservation communities in the state of North Dakota with American Indian adults between the ages of 30 and 75 years. We utilized purposive sampling to ensure maximum variation in age, sex, and tribal community until data saturation was achieved. The interviews were transcribed, and thematic analysis was carried out to identify consistent themes rooted within the data. Ethical approval was gained for this project from all relevant institutional review boards. RESULTS: Four main themes were identified as barriers for the engagement with colorectal cancer prevention, including: colorectal cancer screening barriers, focused on other health problems, lack of colorectal cancer tailored health promotion, and socio-cultural factors affecting colorectal cancer prevention. Three main themes were identified as facilitators for the engagement with colorectal cancer prevention, including: reasons for getting colorectal cancer screening, role of culture, and getting out into the community. CONCLUSION: There is need for more community-rooted, strengths-based approaches to colorectal cancer prevention activities in AI communities in North Dakota. Socio-cultural factors, such as the use of storytelling, and the use of traditional knowledge have been demonstrated to be an important element of consideration for colorectal cancer tribal community engagement and prevention planning in the state.

The association of health insurance and race with treatment and survival in patients with metastatic colorectal cancer.

BACKGROUND: Black patients and underinsured patients with colorectal cancer (CRC) present with more advanced disease and experience worse outcomes. The study aim was to evaluate the interaction of health insurance status and race with treatment and survival in metastatic CRC. MATERIALS AND METHODS: Patients diagnosed with metastatic CRC within NCDB from 2006-2016 were included. Primary outcomes included receipt of chemotherapy and 3-year all-cause mortality. Multivariable logistic regression and Cox-regression (MVR) including a two-way interaction term of race and insurance were performed to evaluate the differential association of race and insurance with receipt of chemotherapy and mortality, respectively. RESULTS: 128,031 patients were identified; 70.6% White, 14.4% Black, 5.7% Hispanic, and 9.3% Other race. Chemotherapy use was higher among White compared to Black patients. 3-year mortality rate was higher for Blacks and lower for Hispanics, in comparison with White patients. By MVR, Black patients were less likely to receive chemotherapy. When stratified by insurance status, Black patients with private and Medicare insurance were less likely to receive chemotherapy than White patients. All-cause mortality was higher in Black patients and lower in Hispanic patients, and these differences persisted after controlling for insurance and receipt of chemotherapy. CONCLUSION: Black patients and uninsured or under-insured patients with metastatic CRC are less likely to receive chemotherapy and have increased mortality. The effect of health insurance among Blacks and Whites differs, however, and improving insurance alone does not appear to fully mitigate racial disparities in treatment and outcomes.

Polygenic risk prediction models for colorectal cancer: a systematic review.

BACKGROUND: Risk prediction models incorporating single nucleotide polymorphisms (SNPs) could lead to individualized prevention of colorectal cancer (CRC). However, the added value of incorporating SNPs into models with only traditional risk factors is still not clear. Hence, our primary aim was to summarize literature on risk prediction models including genetic variants for CRC, while our secondary aim was to evaluate the improvement of discriminatory accuracy when adding SNPs to a prediction model with only traditional risk factors. METHODS: We conducted a systematic review on prediction models incorporating multiple SNPs for CRC risk prediction. We tested whether a significant trend in the increase of Area Under Curve (AUC) according to the number of SNPs could be observed, and estimated the correlation between AUC improvement and number of SNPs. We estimated pooled AUC improvement for SNP-enhanced models compared with non-SNP-enhanced models using random effects meta-analysis, and conducted meta-regression to investigate the association of specific factors with AUC improvement. RESULTS: We included 33 studies, 78.79% using genetic risk scores to combine genetic data. We found no significant trend in AUC improvement according to the number of SNPs (p for trend = 0.774), and no correlation between the number of SNPs and AUC improvement (p = 0.695). Pooled AUC improvement was 0.040 (95% CI: 0.035, 0.045), and the number of cases in the study and the AUC of the starting model were inversely associated with AUC improvement obtained when adding SNPs to a prediction model. In addition, models constructed in Asian individuals achieved better AUC improvement with the incorporation of SNPs compared with those developed among individuals of European ancestry. CONCLUSIONS: Though not conclusive, our results provide insights on factors influencing discriminatory accuracy of SNP-enhanced models. Genetic variants might be useful to inform stratified CRC screening in the future, but further research is needed.

CDH1 germline variants are enriched in patients with colorectal cancer, gastric cancer, and breast cancer.

BACKGROUND AND AIMS: CDH1 germline variants have been linked to heritability in diffuse gastric (DGC) and lobular breast cancer (LBC). Studies have not yet assessed whether CDH1 is a cancer-susceptibility gene in other cancers. Herein, we mapped the landscape of pathogenic and likely pathogenic (P/LP) germline variants in CDH1 across various cancers and ethnicities. METHODS: We evaluated CDH1 germline P/LP variants in 212,944 patients at one CLIA-certified laboratory (Invitae) and described their frequency in 7 cancer types. We screened for CDH1 variant enrichment in each cancer relative to a cancer-free population from The Genome Aggregation Database version 3 (gnomADv3). RESULTS: CDH1 P/LP variants were identified in 141 patients, most commonly in patients with DGC (27/408, 6.6%) followed by colorectal signet-ring cell cancer (CSRCC; 3/79, 3.8%), gastric cancer (56/2756, 2%), and LBC (22/6809, 0.3%). CDH1 P/LP variants were enriched in specific ethnic populations with breast cancer, gastric cancer, CRC, LBC, DGC, and CSRCC compared to matched ethnicities from gnomADv3. CONCLUSION: We report for the first time the prevalence of P/LP CDH1 variants across several cancers and show significant enrichment in CDH1 P/LP variants for patients with CSRCC, DGC, and LBC across various ethnicities. Future prospective studies are warranted to validate these findings.

Barriers and Facilitators to Colorectal Cancer Screening in African-American Men.

BACKGROUND: African-Americans rank last among all racial groups for age-adjusted colorectal cancer mortality, 5-year survival rates, and rates of screening. Access to care does not fully explain racial disparities in rates of CRC and mortality. Sociocultural attitudes can predict probabilities of CRC screening. AIMS: The objective of this study is to identify factors that influence colorectal cancer screening behavior in African-American men. METHODS: Semi-structured interviews were conducted among 32 African-American men. Transcripts were analyzed using MAXQDA software. We then conducted a cross-sectional survey of 103 African-American men, using previously validated scales related to colorectal cancer screening and determinants. Data were analyzed with SPSS. RESULTS: In the interview phase, beliefs relating to masculinity emerged as factors that hindered participation in screening. Overwhelmingly, participants felt that having an in-depth discussion about colorectal cancer with their provider was critical to enabling them to get screened. The survey phase demonstrated that most participants had poor colorectal cancer knowledge, as only 16% passed the knowledge test. Forty-eight percentage agreed that their provider did not recommend getting screened. Those who had been previously screened for colorectal cancer scored higher in total and on all subsets of the masculinity index than those who had not (p < .01). The most persuasive messages were those related to themes of masculinity. CONCLUSION: This study provides a novel sociocultural perspective about colorectal cancer screening in African-American men. Our findings highlight the importance of family, masculinity, and community when promoting colorectal cancer screening to this population.