SpaceANOVA: Spatial Co-occurrence Analysis of Cell Types in Multiplex Imaging Data Using Point Process and Functional ANOVA.

Multiplex imaging platforms have enabled the identification of the spatial organization of different types of cells in complex tissue or the tumor microenvironment. Exploring the potential variations in the spatial co-occurrence or colocalization of different cell types across distinct tissue or disease classes can provide significant pathological insights, paving the way for intervention strategies. However, the existing methods in this context either rely on stringent statistical assumptions or suffer from a lack of generalizability. We present a highly powerful method to study differential spatial co-occurrence of cell types across multiple tissue or disease groups, based on the theories of the Poisson point process and functional analysis of variance. Notably, the method accommodates multiple images per subject and addresses the problem of missing tissue regions, commonly encountered due to data-collection complexities. We demonstrate the superior statistical power and robustness of the method in comparison with existing approaches through realistic simulation studies. Furthermore, we apply the method to three real data sets on different diseases collected using different imaging platforms. In particular, one of these data sets reveals novel insights into the spatial characteristics of various types of colorectal adenoma.

Implementation Mapping for Managing Patients at High Risk for Hereditary Cancer.

INTRODUCTION: Currently, no standard workflow exists for managing patients with pathogenic variants that put them at higher risk for hereditary cancers. Therefore, follow-up care for individuals with pathogenic variants is logistically challenging and results in poor guideline adherence. To address this challenge, authors created clinical management strategies for individuals identified at high risk for hereditary cancers. METHODS: An implementation mapping approach was used to develop and evaluate the establishment of a Hereditary Cancer Clinic at the Medical University of South Carolina throughout in 2022. This approach consisted of 5 steps: conduct a needs assessment, identify objectives, select implementation strategies, produce implementation protocols, and develop an evaluation plan. The needs assessment consisted of qualitative interviews with patients (n=11), specialists (n=9), and members of the implementation team (n=4). Interviews were coded using the Consolidated Framework for Implementation Research to identify barriers and facilitators to establishment of the Hereditary Cancer Clinic. Objectives were identified, and then the team selected implementation strategies and produced implementation protocols to address concerns identified during the needs assessment. Authors conducted a second round of patient interviews to assess patient education materials. RESULTS: The research team developed a long-term evaluation plan to guide future assessment of implementation, service, and clinical/patient outcomes. CONCLUSIONS: This approach provides the opportunity for real-time enhancements and impact, with strategies for care specialists, patients, and implementation teams. Findings support ongoing efforts to improve patient management and outcomes while providing an opportunity for long-term evaluation of implementation strategies and guidelines for patients at high risk for hereditary cancers.

A Bayesian framework for pathway-guided identification of cancer subgroups by integrating multiple types of genomic data.

In recent years, comprehensive cancer genomics platforms, such as The Cancer Genome Atlas (TCGA), provide access to an enormous amount of high throughput genomic datasets for each patient, including gene expression, DNA copy number alterations, DNA methylation, and somatic mutation. While the integration of these multi-omics datasets has the potential to provide novel insights that can lead to personalized medicine, most existing approaches only focus on gene-level analysis and lack the ability to facilitate biological findings at the pathway-level. In this article, we propose Bayes-InGRiD (Bayesian Integrative Genomics Robust iDentification of cancer subgroups), a novel pathway-guided Bayesian sparse latent factor model for the simultaneous identification of cancer patient subgroups (clustering) and key molecular features (variable selection) within a unified framework, based on the joint analysis of continuous, binary, and count data. By utilizing pathway (gene set) information, Bayes-InGRiD does not only enhance the accuracy and robustness of cancer patient subgroup and key molecular feature identification, but also promotes biological understanding and interpretation. Finally, to facilitate an efficient posterior sampling, an alternative Gibbs sampler for logistic and negative binomial models is proposed using Pólya-Gamma mixtures of normal to represent latent variables for binary and count data, which yields a conditionally Gaussian representation of the posterior. The R package "INGRID" implementing the proposed approach is currently available in our research group GitHub webpage (https://dongjunchung.github.io/INGRID/).

SpaceANOVA: Spatial co-occurrence analysis of cell types in multiplex imaging data using point process and functional ANOVA.

Motivation: Multiplex imaging platforms have enabled the identification of the spatial organization of different types of cells in complex tissue or tumor microenvironment (TME). Exploring the potential variations in the spatial co-occurrence or co-localization of different cell types across distinct tissue or disease classes can provide significant pathological insights, paving the way for intervention strategies. However, the existing methods in this context either rely on stringent statistical assumptions or suffer from a lack of generalizability. Results: We present a highly powerful method to study differential spatial co-occurrence of cell types across multiple tissue or disease groups, based on the theories of the Poisson point process (PPP) and functional analysis of variance (FANOVA). Notably, the method accommodates multiple images per subject and addresses the problem of missing tissue regions, commonly encountered in such a context due to the complex nature of the data-collection procedure. We demonstrate the superior statistical power and robustness of the method in comparison to existing approaches through realistic simulation studies. Furthermore, we apply the method to three real datasets on different diseases collected using different imaging platforms. In particular, one of these datasets reveals novel insights into the spatial characteristics of various types of precursor lesions associated with colorectal cancer. Availability: The associated R package can be found here, https://github.com/sealx017/SpaceANOVA.

Association of Preventive Care Attitudes and Beliefs with Colorectal Cancer Screening History among African American Patients of Community Health Centers.

Colorectal cancer (CRC) is the third most common cancer and third leading cause of cancer-related death among African Americans in the United States. However, when detected early, CRC is treatable and survival rates are high. CRC health disparities for African Americans compared with other groups may be due in part to lower screening adherence and later stage diagnosis. The objective of this research phase was to test predictors of ever having received CRC screening (i.e., self-report of lifetime receipt of CRC screening) using survey measures in the domains of healthcare communication, trust in doctors, CRC perceived susceptibility, CRC worry, negative cancer beliefs, CRC screening self-efficacy, and cultural constructs for CRC screening in a sample of African American community health center patients. The study recruited 115 African American patients between the ages of 45 to 64 years old from community health centers in north Florida to complete the baseline survey. Our results show significant differences in CRC screening history by age, marital status, level of mistrust of healthcare providers, and level of empowerment toward cancer screening. To increase CRC screening in this population, the study findings suggest development of intervention programs that focus on priority populations of younger, unmarried African Americans, especially given the current trend of early onset CRC. Moreover, survival rates are lower for unmarried and younger African Americans relative to older and married individuals. Such interventions should also aim to increase trust in healthcare providers and increase empowerment for CRC screening decision making to increase screening participation.

Genetic Associations with Smoking Relapse and Proportion of Follow-up in Smoking Relapse throughout Adulthood in Pre- and Postmenopausal Women.

PREVENTION RELEVANCE: This study is the first to quantify genetic associations with smoking relapse among female smokers throughout adulthood. These findings could inform precision medicine approaches to improve long-term smoking relapse prevention to reduce smoking attributable cancer morbidity and mortality.

CHRNA5-A3-B4 and DRD2 Genes and Smoking Cessation Throughout Adulthood: A Longitudinal Study of Women.

INTRODUCTION: Smoking cessation is more than 50% heritable. Genetic studies of smoking cessation have been limited by short-term follow-up or cross-sectional design. AIMS AND METHODS: This study tests single nucleotide polymorphism (SNP) associations with cessation during long-term follow-up throughout adulthood in women. The secondary aim tests whether genetic associations differ by smoking intensity. Associations between 10 SNPs in CHRNA5, CHRNA3, CHRNB2, CHRNB4, DRD2, and COMT and the probability of smoking cessation over time were evaluated in two longitudinal cohort studies of female nurses, the Nurses' Health Study (NHS) (n = 10 017) and NHS-2 (n = 2793). Participant follow-up ranged from 2 to 38 years with data collected every 2 years. RESULTS: Women with the minor allele of either CHRNA5 SNP rs16969968 or CHRNA3 SNP rs1051730 had lower odds of cessation throughout adulthood [OR = 0.93, p-value = .003]. Women had increased odds of cessation if they had the minor allele of CHRNA3 SNP rs578776 [OR = 1.17, p-value = .002]. The minor allele of DRD2 SNP rs1800497 was associated with lower odds of cessation in moderate-to-heavy smokers [OR = 0.92, p-value = .0183] but increased odds in light smokers [OR = 1.24, p-value = .096]. CONCLUSIONS: Some SNP associations with short-term smoking abstinence observed in prior studies were shown in the present study to persist throughout adulthood over decades of follow-up. Other SNP associations with short-term abstinence did not persist long-term. The secondary aim findings suggest genetic associations may differ by smoking intensity. IMPLICATIONS: The results of the present study expand on previous studies of SNP associations in relation to short-term smoking cessation to demonstrate some of these SNPs were associated with smoking cessation throughout decades of follow-up, whereas other SNP associations with short-term abstinence did not persist long-term. The rate of relapse to smoking remains high for several years after quitting smoking, and many smokers experience multiple quit attempts and relapse episodes throughout adulthood. Understanding genetic associations with long-term cessation has potential importance for precision medicine approaches to long-term cessation management.

Utilizing multimodal mass spectrometry imaging for profiling immune cell composition and N-glycosylation across colorectal carcinoma disease progression.

Colorectal cancer (CRC) stands as a leading cause of death worldwide, often arising from specific genetic mutations, progressing from pre-cancerous adenomas to adenocarcinomas. Early detection through regular screening can result in a 90% 5-year survival rate for patients. However, unfortunately, only a fraction of CRC cases are identified at pre-invasive stages, allowing progression to occur silently over 10-15 years. The intricate interplay between the immune system and tumor cells within the tumor microenvironment plays a pivotal role in the progression of CRC. Immune cell clusters can either inhibit or facilitate tumor initiation, growth, and metastasis. To gain a better understanding of this relationship, we conducted N-glycomic profiling using matrix-assisted laser desorption-ionization mass spectrometry imaging (MALDI-MSI). We detected nearly 100 N-glycan species across all samples, revealing a shift in N-glycome profiles from normal to cancerous tissues, marked by a decrease in high mannose N-glycans. Further analysis of precancerous to invasive carcinomas showed an increase in pauci-mannose biantennary, and tetraantennary N-glycans with disease progression. Moreover, a distinct stratification in the N-glycome profile was observed between non-mucinous and mucinous CRC tissues, driven by pauci-mannose, high mannose, and bisecting N-glycans. Notably, we identified immune clusters of CD20+ B cells and CD3/CD44+ T cells distinctive and predictive with signature profiles of bisecting and branched N-glycans. These spatial N-glycan profiles offer potential biomarkers and therapeutic targets throughout the progression of CRC.

A systematic review of genetic variation within nicotinic acetylcholine receptor genes and cigarette smoking cessation.

BACKGROUND: Nicotine produces its effects by binding to nicotinic acetylcholine receptors (nAChRs). Variants of genes encoding properties of nAChRs are candidates for affecting likelihood of smoking cessation. METHODS: A systematic review was conducted summarizing evidence of associations between single nucleotide polymorphisms (SNPs) of nAChR genes and smoking cessation. From 24 articles meeting inclusion criteria, summary odds ratios (ORs) for associations between nine SNPs and smoking cessation were calculated from 26 studies (N = 233-29,072) stratified by gene, ancestry, study design, and pharmacotherapy; SNPs in linkage disequilibrium were pooled. Results for a tenth SNP from two GWAS were summarized. RESULTS: People of European ancestry with minor alleles of CHRNA5 rs16969968 and CHRNA3 rs1051730 had longer time to cessation [HR = 0.90, 95 % CI 0.88 - 0.92 (n = 2 studies)] and lower odds of cessation [OR = 0.88, 95 % CI 0.80 - 0.97 (n = 5 cohort studies), OR = 0.64, 95 % CI 0.45 - 0.90 (n = 4 placebo arms)]. Risk of persistent smoking associated with these alleles was attenuated in smokers receiving nicotine replacement therapy (NRT). Recipients of bupropion alone or with NRT with these alleles had higher, though not statistically significant, odds of cessation. Results for CHRNA5 rs588765 and rs680244 were similar to rs16969968/rs1051730 findings. Evidence was limited for other SNPs. CONCLUSION: Evidence consistently indicates the minor alleles of four SNPs within CHRNA3 or CHRNA5 are risk alleles for cessation failure. Analysis by pharmacotherapy revealed bupropion may be the most efficacious intervention for people with these alleles.

Association of age with survival in older patients with cutaneous melanoma treated with immune checkpoint inhibitors.

INTRODUCTION: Several types of immune checkpoint inhibitors (ICIs) are approved to treat advanced melanoma, but their effectiveness has not been compared in older patients treated outside of a clinical trial. Moreover, evidence suggests that a patient's response to ICI therapy may vary by age and type of ICI. The purpose of this study was to compare survival by ICI type in older patients with melanoma and to investigate treatment effect modification by age. MATERIALS AND METHODS: Using the SEER-Medicare database, we identified patients with cutaneous melanoma (2012-2015) treated with an ICI (CTLA-4, PD-1, or combination CTLA-4 + PD-1 inhibitors). Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for ICI types. We used an interaction term and stratified models to test for treatment effect modification by age. RESULTS: Of the 1435 patients included in our analysis, 790 (55.1%) received CTLA-4 inhibitors, 512 (35.7%) received PD-1 inhibitors, and 133 (9.3%) were treated with combination ICIs. Median survival ranged from 13.4 months (95%CI: 10.7-16.3) for CTLA-4 inhibitors to 23.5 months (95%CI: 16.2-30.0) for combination ICIs. In multivariable models, the risk of death was lower with PD-1 inhibitors compared to CTLA-4 inhibitors (HR = 0.78, 95%CI: 0.68-0.89). An age*ICI type interaction term was significant (p < 0.001), and survival gains were greater the older age group (≥80) compared to the younger group (65-79). DISCUSSION: In a population-based setting, we identified important differences in survival by ICI type in older patients with melanoma treated with ICIs, with prolonged survival associated with PD-1 inhibitors compared to CTLA-4 inhibitors.

Predictors of Incident Serrated Polyps: Results from a Large Multicenter Clinical Trial.

BACKGROUND: Serrated polyps (SP) are important colorectal cancer precursors, yet their epidemiology is incompletely understood. We measured risk factors for incident sessile-serrated lesions (SSL) and microvesicular (MVHP) and goblet-cell rich (GCHP) hyperplastic polyp subtypes. METHODS: We conducted a cohort study of patients undergoing colonoscopic surveillance nested within a chemoprevention trial. Outcomes of interest were ≥1 SPs, including SSLs, MVHPs, and GCHPs specifically. Multivariable generalized estimating equation models were used to estimate adjusted risk ratios (RR) and 95% confidence intervals (CI) for different polyp types. RESULTS: Among 2,102 participants, a total of 1,615 SPs (including 212 SSLs) were found among 758 participants during follow-up. Prior history of SPs was strongly associated with subsequent occurrence of SPs. There was no apparent association between age, sex, or education and risk of SPs. Black participants were at lower risk of SSLs and MVHPs, but higher risk of GCHPs compared with white participants [RR, 0.40; 95% CI, 0.16-0.99); RR, 0.63 (95% CI, 0.42-0.96); and RR, 1.83 (95% CI, 1.23-2.72) respectively]. Alcohol and smoking exposure were also associated with SPs, including hyperplastic polyp subtypes in particular. CONCLUSIONS: In this prospective study, the risk of SP subtypes differed by race, alcohol, and smoking status, and prior history of SPs. Risk factor associations for SPs differ from risk factors for conventional adenomas, supporting the concept of etiologic heterogeneity of colorectal cancer. IMPACT: These findings allow for better risk stratification of patients undergoing colorectal cancer screening and could inform screening test selection.

Assessing the effectiveness of a community health advisor plus screen to save educational intervention on stool-based testing adherence in an African American safety net clinic population: study protocol for a randomized pragmatic trial.

BACKGROUND: Colorectal cancer (CRC) is the second most deadly cancer affecting US adults and is also one of the most treatable cancers when detected at an earlier clinical stage of disease through screening. CRC health disparities experienced by African Americans are due in part to the later stage of diagnosis, suggesting the importance of improving African Americans' CRC screening participation. The national Screen to Save (S2S) initiative employs a community health educator to deliver CRC screening education which can be tailored for specific populations, and such approaches have increased CRC screening rates in disadvantaged and racial/ethnic minority populations. METHODS/DESIGN: In this trial emphasizing stool-based CRC screening, focus groups informed the development of an adapted S2S video and brochure tailored for African Americans and identified preferred motivational text messages for a multicomponent community health advisor (CHA) intervention. A CHA hired from the community was trained to deliver a 6-week CRC educational intervention consisting of an initial face-to-face meeting followed by 5 weeks of calls and texts. Interested eligible persons are enrolled primarily through recruitment by two partnering community health centers (CHCs) and secondarily through various outreach channels and, after consenting and completing a baseline survey, are randomly assigned to one of two study arms. The CHCs are blinded to study arm assignment. Intervention arm participants receive the brochure and CHA intervention while participants assigned to the control group receive only the brochure. All participants receive a stool-based CRC screening test from their health center, and the primary outcome is the completion of the screening test at 12 months. Secondary objectives are to estimate the effect of the intervention on mediating factors, explore the effect of moderating factors, and perform a cost-effectiveness analysis of the CHA intervention. DISCUSSION: The TUNE-UP study will enhance understanding about CRC screening in African Americans obtaining primary health care through CHCs and is one of the very few studies to examine a CHA intervention in this context. A better understanding of the mechanisms by which the intervention affects patient beliefs and behaviors will help focus future research while the exploratory cost-effectiveness analysis will inform CHCs' decision-making about implementing a CHA program to increase screening and reduce cancer health disparities. TRIAL REGISTRATION: ClinicalTrials.gov NCT04304001 . Registered on March 11, 2020.

Engaging the Community on Colorectal Cancer Screening Education: Focus Group Discussions Among African Americans.

Colorectal cancer (CRC) is the third most diagnosed cancer in the USA, and African Americans experience disproportionate CRC diagnosis and mortality. Early detection could reduce CRC incidence and mortality, and reduce CRC health disparities, which may be due in part to lower screening adherence and later stage diagnosis among African Americans compared to whites. Culturally tailored interventions to increase access to and uptake of CRC stool-based tests are one effective strategy to increase benefits of screening among African Americans. The objectives of this study were to obtain feedback from African Americans on CRC educational materials being developed for a subsequent behavioral clinical trial and explore participants' knowledge, attitudes, and beliefs about CRC and CRC screening. Seven focus groups were conducted between February and November 2020. Participants were African Americans recruited through community contacts. Four focus groups were held in-person and three were conducted virtually due to Covid-19 restrictions. Participants ranked CRC educational text messages and provided feedback on a culturally tailored educational brochure. A focus group guide with scripted probes was used to elicit discussion and transcripts were analyzed using traditional content analysis. Forty-two African Americans participated. Four themes were identified from focus group discussions: (1) knowledge, attitudes, and beliefs on CRC and CRC screening; (2) reliable sources of cancer education information; (3) cultural factors affecting perspectives on health; and (4) community insights into cancer education. Participant input on the brochure was incorporated in content creation. Engaging African American community members to qualitatively examine cancer prevention has value in improving implementation strategy and planning for behavioral clinical trials.

Nicotine Metabolism Predicted by CYP2A6 Genotypes in Relation to Smoking Cessation: A Systematic Review.

INTRODUCTION: Identifying genetic factors associated with smoking cessation could inform precision cessation interventions. Of major interest is genetic variation in nicotine metabolism, largely predicted by CYP2A6 variations. AIMS AND METHODS: We conducted a systematic literature review to summarize the population-based evidence of the association between CYP2A6 and smoking cessation. In the 12 studies meeting the inclusion criteria, the known functional metabolic effect of CYP2A6 variants was used to classify nicotine metabolism as normal (>75% metabolic activity), intermediate (50.1%-75% activity), slow (25%-50% activity), and poor (<25% activity). Summary odds ratios of smoking cessation were calculated across metabolic groups, stratified by ancestry and whether participants received pharmacotherapy or placebo/no treatment. RESULTS: Among untreated people of European ancestry (n = 4 studies), those with CYP2A6 reduced metabolism were more likely to quit smoking than those with normal metabolism (Summary OR = 2.05, 95% CI 1.23 to 3.42) and the likelihood of cessation increased as nicotine metabolism decreased. Nicotine replacement therapy attenuated the association at end-of-treatment, while bupropion modified the association such that intermediate/slow metabolizers were less likely to quit than normal metabolizers (Summary OR = 0.86, 95% CI 0.79 to 0.94). Among untreated Asian people (n = 3 studies), results differed compared with those with European ancestry: those with slow metabolism were less likely to have quit smoking than normal metabolizers (Summary OR = 0.52, 95% CI 0.38 to 0.71). Evidence for people of African ancestry (n = 1 study) suggested the CYP2A6 association with cessation may differ compared with those of European ancestry. CONCLUSIONS AND IMPLICATIONS: Most studies included in this review were of European ancestry populations; these showed slower nicotine metabolism was associated with increased likelihood of smoking cessation in a dose-related manner. Pharmacotherapy appeared to attenuate or modify this association among people of European ancestry, but it is unclear whether the change in the association remains consistent after treatment ceases. This finding has implications for precision medicine cessation interventions. Based on only a few studies of people of Asian or African ancestry, the association between CYP2A6 variants and cessation may differ from that observed among those of European ancestry, but more evidence is needed.

Immune Responses Vary in Preinvasive Colorectal Lesions by Tumor Location and Histology.

Immune responses vary in colorectal cancers, which strongly influence prognosis. However, little is known about the variance in immune response within preinvasive lesions. The study aims to investigate how the immune contexture differs by clinicopathologic features (location, histology, dysplasia) associated with progression and recurrence in early carcinogenesis. We performed a cross-sectional study using preinvasive lesions from the surgical pathology laboratory at the Medical University of South Carolina. We stained the tissues with immunofluorescence antibodies, then scanned and analyzed expression using automated image analysis software. We stained CD117 as a marker of mast cells, CD4/RORC to indicate Th17 cells, MICA/B as a marker of NK-cell ligands, and also used antibodies directed against cytokines IL6, IL17A, and IFNγ. We used negative binomial regression analysis to compare analyte density counts by location, histology, degree of dysplasia adjusted for age, sex, race, and batch. All immune markers studied (except IL17a) had significantly higher density counts in the proximal colon than distal colon and rectum. Increases in villous histology were associated with significant decreases in immune responses for IL6, IL17a, NK ligand, and mast cells. No differences were observed in lesions with low- and high-grade dysplasia, except in mast cells. The lesions of the proximal colon were rich in immune infiltrate, paralleling the responses observed in normal mucosa and invasive disease. The diminishing immune response with increasing villous histology suggests an immunologically suppressive tumor environment. Our findings highlight the heterogeneity of the immune responses in preinvasive lesions, which may have implications for prevention strategies. PREVENTION RELEVANCE: Our study is focused on immune infiltrate expression in preinvasive colorectal lesions; our results suggest important differences by clinicopathologic features that have implications for immune prevention research.

Preinvasive Colorectal Lesions of African Americans Display an Immunosuppressive Signature Compared to Caucasian Americans.

BACKGROUND: African Americans (AAs) have higher colorectal cancer (CRC) incidence and mortality rate than Caucasian Americans (CAs). Recent studies suggest that immune responses within CRCs contribute to the disparities. If racially distinct immune signatures are present in the early phases of carcinogenesis, they could be used to develop interventions to prevent or slow disease. METHODS: We selected a convenience sample of 95 patients (48 CAs, 47 AAs) with preinvasive colorectal adenomas from the surgical pathology laboratory at the Medical University of South Carolina. Using immunofluorescent-conjugated antibodies on tissue slides from the lesions, we quantified specific immune cell populations: mast cells (CD117+), Th17 cells (CD4+RORC+), and NK cell ligand (MICA/B) and inflammatory cytokines, including IL-6, IL-17A, and IFN-γ. We compared the mean density counts (MDCs) and density rate ratios (RR) and 95% CI of immune markers between AAs to CAs using negative binomial regression analysis. We adjusted our models for age, sex, clinicopathologic characteristics (histology, location, dysplasia), and batch. RESULTS: We observed no racial differences in age or sex at the baseline endoscopic exam. AAs compared to CAs had a higher prevalence of proximal adenomas (66% vs. 40%) and a lower prevalence of rectal adenomas (11% vs. 23%) (p =0.04) but no other differences in pathologic characteristics. In age, sex, and batch adjusted models, AAs vs. CAs had lower RRs for cells labeled with IFNγ (RR 0.50 (95% CI 0.32-0.81); p=0.004) and NK cell ligand (RR 0.67 (0.43-1.04); p=0.07). In models adjusted for age, sex, and clinicopathologic variables, AAs had reduced RRs relative to CAs for CD4 (p=0.02), NK cell ligands (p=0.01), Th17 (p=0.005), mast cells (p=0.04) and IFN-γ (p< 0.0001). CONCLUSIONS: Overall, the lower RRs in AAs vs. CAs suggests reduced effector response capacity and an immunosuppressive ('cold') tumor environment. Our results also highlight the importance of colonic location of adenoma in influencing these differences; the reduced immune responses in AAs relative to CAs may indicate impaired immune surveillance in early carcinogenesis. Future studies are needed to understand the role of risk factors (such as obesity) in influencing differences in immune responses by race.

Differential immune signatures in the tumor microenvironment are associated with colon cancer racial disparities.

BACKGROUND: Disparities in colon cancer (CC) outcomes may be due to a more aggressive phenotype in African American patients in the setting of a decreased tumor immunity, though the precise mechanism for this result has not been well elucidated. To explore the molecular factors underlying CC disparities, we compared the immunogenomic signatures of CC from African American and European American patients. METHODS: We identified all CC patients from the publicly available Cancer Genome Atlas for whom race and survival data are available. Immunophenotype signatures were established for African American and European American patients. Comparisons were made regarding survival and a multivariable linear regression model was created to determine the association of immune cellular components with race. Differential gene expression was also assessed. RESULTS: Of the 254 patients identified, 58 (23%) were African American and 196 (77%) were European American. African American patients had a decreased progression free survival (p = 0.04). Tumors from African American patients displayed a reduced fraction of macrophages and CD8+ T cells and an increased fraction of B cells compared with tumors from European Americans. Differences persisted when controlling for sex, age, and disease stage. Immunostimulatory and immunoinhibitory gene profiles including major histocompatibility complex expression differed by race. CONCLUSIONS: Differences in the tumor immune microenvironment of African American as compared to European American CC specimens may play a role in the survival differences between the groups. These differences may provide targeted therapeutic opportunities.

A cohort study of personal and family history of skin cancer in relation to all-cause and cancer-specific mortality.

PURPOSE: Even though the fatality rate from skin cancers is low, evidence from a few cohort studies has raised the possibility that people with a personal history of skin cancer may have a higher all-cause mortality rate compared with those without a personal history of skin cancer. The purpose of the present study was to investigate the potential links between a personal history or family history of skin cancer and all-cause and cancer-specific mortality METHODS: A prospective cohort (n = 8,622) was assembled within the NHANES I follow-up study. Cox Proportional Hazard Regression analysis was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association for personal and family history of skin cancer and all-cause and cancer-specific mortality. RESULTS: After adjustment for several potential confounding variables, a personal history of skin cancer was associated with decreased risk for all-cause mortality (HR 0.72, 95% CI 0.61-0.85), whereas the results for cancer-specific mortality were consistent with a null association (HR 0.97, 95% CI 0.74-1.27). A family history of skin cancer was not significantly associated with all-cause mortality (HR 0.97, 95% CI 0.76-1.24) or cancer-specific mortality (HR 0.69, 95% CI 0.38-1.24). CONCLUSION: The results of the present study do not support the hypothesis that a personal history or family history of skin cancer is associated with an increased risk of all-cause or cancer-specific mortality. The high prevalence of skin cancer adds to the public health significance of this question, providing a strong rationale for further research to resolve this question.

Adaptation of a Community Health Advisor Intervention to Increase Colorectal Cancer Screening Among African Americans in the Southern United States.

Community health advisor (CHA) interventions increase colorectal cancer (CRC) screening rates. African Americans experience CRC disparities in incidence and mortality rates compared to whites in the US. Focus groups and learner verification were used to adapt National Cancer Institute CRC screening educational materials for delivery by a CHA to African American community health center patients. Such academic-community collaboration improves adoption of evidence-based interventions. This short article describes the adaptation of an evidence-based cancer education intervention for implementation in an African American community.

A deep learning segmentation strategy that minimizes the amount of manually annotated images.

Deep learning has revolutionized the automatic processing of images. While deep convolutional neural networks have demonstrated astonishing segmentation results for many biological objects acquired with microscopy, this technology's good performance relies on large training datasets. In this paper, we present a strategy to minimize the amount of time spent in manually annotating images for segmentation. It involves using an efficient and open source annotation tool, the artificial increase of the training data set with data augmentation, the creation of an artificial data set with a conditional generative adversarial network and the combination of semantic and instance segmentations. We evaluate the impact of each of these approaches for the segmentation of nuclei in 2D widefield images of human precancerous polyp biopsies in order to define an optimal strategy.