Translation of Epigenetics in Cell-Free DNA Liquid Biopsy Technology and Precision Oncology.

Technological advancements in cell-free DNA (cfDNA) liquid biopsy have triggered exponential growth in numerous clinical applications. While cfDNA-based liquid biopsy has made significant strides in personalizing cancer treatment, the exploration and translation of epigenetics in liquid biopsy to clinical practice is still nascent. This comprehensive review seeks to provide a broad yet in-depth narrative of the present status of epigenetics in cfDNA liquid biopsy and its associated challenges. It highlights the potential of epigenetics in cfDNA liquid biopsy technologies with the hopes of enhancing its clinical translation. The momentum of cfDNA liquid biopsy technologies in recent years has propelled epigenetics to the forefront of molecular biology. We have only begun to reveal the true potential of epigenetics in both our understanding of disease and leveraging epigenetics in the diagnostic and therapeutic domains. Recent clinical applications of epigenetics-based cfDNA liquid biopsy revolve around DNA methylation in screening and early cancer detection, leading to the development of multi-cancer early detection tests and the capability to pinpoint tissues of origin. The clinical application of epigenetics in cfDNA liquid biopsy in minimal residual disease, monitoring, and surveillance are at their initial stages. A notable advancement in fragmentation patterns analysis has created a new avenue for epigenetic biomarkers. However, the widespread application of cfDNA liquid biopsy has many challenges, including biomarker sensitivity, specificity, logistics including infrastructure and personnel, data processing, handling, results interpretation, accessibility, and cost effectiveness. Exploring and translating epigenetics in cfDNA liquid biopsy technology can transform our understanding and perception of cancer prevention and management. cfDNA liquid biopsy has great potential in precision oncology to revolutionize conventional ways of early cancer detection, monitoring residual disease, treatment response, surveillance, and drug development. Adapting the implementation of liquid biopsy workflow to the local policy worldwide and developing point-of-care testing holds great potential to overcome global cancer disparity and improve cancer outcomes.

Population-based evaluation of disparities in stomach cancer by nativity among Asian and Hispanic populations in California, 2011-2015.

BACKGROUND: Stomach cancer incidence presents significant racial/ethnic disparities among racial/ethnic minority groups in the United States, particularly among Asian and Hispanic immigrant populations. However, population-based evaluation of disparities by nativity has been scarce because of the lack of nativity-specific population denominators, especially for disaggregated Asian subgroups. Population-based stomach cancer incidence and tumor characteristics by detailed race/ethnicity and nativity were examined. METHODS: Annual age-adjusted incidence rates were calculated by race/ethnicity, sex, and nativity and tumor characteristics, such as stage and anatomic subsite, were evaluated using the 2011-2015 California Cancer Registry data. For Hispanic and Asian populations, nativity-specific population counts were estimated using the US Census and the American Community Survey Public Use Microdata Sample data. RESULTS: During 2011-2015 in California, 14,198 patients were diagnosed with stomach cancer. Annual age-adjusted incidence rates were higher among foreign-born individuals than their US-born counterparts. The difference was modest among Hispanics (∼1.3-fold) but larger (∼2- to 3-fold) among Chinese, Japanese, and Korean Americans. The highest incidence was observed for foreign-born Korean and Japanese Americans (33 and 33 per 100,000 for men; 15 and 12 per 100,000 for women, respectively). The proportion of localized stage disease was highest among foreign-born Korean Americans (44%); a similar proportion was observed among US-born Korean Americans, although numbers were limited. For other Asians and Hispanics, the localized stage proportion was generally lower among foreign-born than US-born individuals and lowest among foreign-born Japanese Americans (23%). CONCLUSIONS: Nativity-specific investigation with disaggregated racial/ethnic groups identified substantial stomach cancer disparities among foreign-born immigrant populations.

Health insurance literacy among patients receiving outpatient cancer treatment.

BACKGROUND: This study examines patients' understanding of health insurance terms and concepts and quantifies health insurance literacy (HIL) levels by key sociodemographic factors. METHODS: This study included 393 adult patients with cancer (>18 years old) receiving treatment in two ambulatory infusion centers: Mayo Clinic in Phoenix, Arizona and the University of Mississippi Medical Center in Jackson, Mississippi. Respondents' perceptions of their HIL were assessed using the Health Insurance Literacy Measure (HILM), a validated 21-item measure of a consumer's ability to select and use health insurance (HIL self-efficacy). Respondents' knowledge of health insurance concepts (HIL knowledge) was measured using 10 items created by the Kaiser Family Foundation. The number of correct answers was categorized into three levels: 0-4 (low knowledge), 5-6 (moderate knowledge), and 7-10 (high knowledge). Multivariable logistic regressions were used to compare correct answers to HIL knowledge questions by HIL self-efficacy. RESULTS: Nearly three-quarters of patients had high HIL self-efficacy and high HIL knowledge (70.5%), understanding basic insurance terms, such as premiums and deductibles. Relatively low percentages of patients correctly answered questions about the meaning of provider networks, health insurance formularies, and calculating out-of-pocket spending in scenarios when insurers pay a portion of allowed charges. Lower HIL knowledge was more common among patients with less educational attainment (

Mentoring Minority Cancer Researchers of Tomorrow: Comparison of the Face-to-Face, Virtual, and Hybrid Training Methods of the CaRE2 Summer Cancer Research Education and Training Program.

In our previous publication, we reported a framework to develop an undergraduate cancer research training program at Florida A&M University (FAMU) under the umbrella of the Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center activity by harnessing the resources available at FAMU, the University of Florida (UF), and the University of Southern California (USC) Cancer Centers. The implementation of the CaRE2 face-to-face training platform was dramatically affected by the COVID-19 pandemic during the summer of 2020 and 2021 training periods. However, a concerted effort was made to restructure the face-to-face training model into virtual and hybrid training methods to maintain the continuity of the program during the pandemic. This article compared the three methods to identify the best platform for training URM students in cancer disparity research. The program's effectiveness was measured through motivation, experiences, and knowledge gained by trainees during and one year after the completion of the program. The results showed that the participants were highly positive in their feedback about the professional and academic values of the program. Although the virtual and hybrid methods experienced significant challenges during the pandemic, the hybrid training module offered an "above average" effectiveness in performance, like the face-to-face mentoring platform in mentoring URM students in cancer disparity research.

Surviving the COVID-19 pandemic: navigating the recovery of breast imaging services in a safety-net hospital.

PURPOSE: The purpose of this study was to determine the impact of COVID-19 on county safety-net breast imaging services and describe the steps taken to actively manage and mitigate delays. METHODS: This was an IRB exempt retrospective review of our county safety-net breast imaging practice analyzed for 4 distinct time periods: (1) "Shut-down period": March 17, 2020 to May 17, 2020; (2) "Phased re-opening": May 18, 2020 to June 30, 2020; (3) "Ramp-up": July 1, 2020 to September 30, 2020; and (4) "Current state": October 1, 2020 to September 30, 2021. These time periods were compared to identical time periods 1 year prior. For "Current state," given that the 1-year prior comparison encompassed the first 3 periods of the pandemic, the identical time period 2 years prior was also compared. RESULTS: Our safety-net practice sustained significant volume losses during the first 3 time periods with a 99% reduction in screening mammography in the shut-down period. Cancers diagnosed decreased by 17% in 2020 (n = 229) compared to 2019 (n = 276). By implementing multiple initiatives that targeted improved access to care, including building community-hospital partnerships and engagement through outreach events and a community education roadshow, we were able to recover and significantly exceed our pandemic screening volumes by 48.1% (27,279 vs 18,419) from October 1, 2020 to September 30, 2021 compared to the identical time period 1 year prior, and exceed our pre-pandemic screening volume by 17.4% (27,279 vs 23,234) compared to the identical time period 2 years prior. CONCLUSION: Through specific community outreach programs and optimized navigation, our safety-net breast imaging practice was able to mitigate the impact of COVID-19 on our patient population by increasing patient engagement and breast imaging services.

Cancer Screening Rates Among Asian Americans: A Cross-Sectional Secondary Data Analysis Study.

PURPOSE: This study aims 1) to investigate recent cancer screening rates among Asian Americans and 2) to test the relationship between race/ethnicity and cancer screening rates. METHODS: This is a cross-sectional secondary data analysis study using data from the 2019 National Health Interview Survey. The screening rates of prostate cancer, colorectal cancer, cervical cancer, and breast cancer among non-Hispanic (NH) Asian Americans, Hispanics, NH Whites, NH African Americans, and NH American Indian and Alaska Natives (AIAN) were analyzed in July 2022. The variables were recoded and analyzed using descriptive analysis and chi-square test. The SPSS version 27 software was used. RESULTS: Descriptive analysis showed a general low screening rate of cancers among Asian Americans, which ranged from 40.5% to 67.5%. The chi-square test suggested significant associations between race/ethnicity and the screening rates of colorectal cancer (P = .002), cervical cancer (P < .01), and breast cancer (P = .021), but not the prostate cancer (P = .472). CONCLUSION: Necessary intervention programs should be designed to increase the uptake rates of cancer screening among Asian Americans.

Differential alternative RNA splicing and transcription events between tumors from African American and White patients in The Cancer Genome Atlas.

Individuals of African ancestry suffer disproportionally from higher incidence, aggressiveness, and mortality for particular cancers. This disparity likely results from an interplay among differences in multiple determinants of health, including differences in tumor biology. We used The Cancer Genome Atlas (TCGA) SpliceSeq and TCGA aggregate expression datasets and identified differential alternative RNA splicing and transcription events (ARS/T) in cancers between self-identified African American (AA) and White (W) patients. We found that retained intron events were enriched among race-related ARS/T. In addition, on average, 12% of the most highly ranked race-related ARS/T overlapped between any two analyzed cancers. Moreover, the genes undergoing race-related ARS/T functioned in cancer-promoting pathways, and a number of race-related ARS/T were associated with patient survival. We built a web-application, CanSplice, to mine genomic datasets by self-identified race. The race-related targets have the potential to aid in the development of new biomarkers and therapeutics to mitigate cancer disparity.

Causes of Socioeconomic Disparities in Colorectal Cancer and Intervention Framework and Strategies.

Colorectal cancer (CRC) disproportionately affects people from low socioeconomic backgrounds and some racial minorities. Disparities in CRC incidence and outcomes might result from differences in exposure to risk factors such as unhealthy diet and sedentary lifestyle; limited access to risk-reducing behaviors such as chemoprevention, screening, and follow-up of abnormal test results; or lack of access to high-quality treatment resources. These factors operate at the individual, provider, health system, community, and policy levels to perpetuate CRC disparities. However, CRC disparities can be eliminated. Addressing the complex factors that contribute to development and progression of CRC with multicomponent, adaptive interventions, at multiple levels of the care continuum, can reduce gaps in mortality. These might be addressed with a combination of health care and community-based interventions and policy changes that promote healthy behaviors and ensure access to high-quality and effective measures for CRC prevention, diagnosis, and treatment. Improving resources and coordinating efforts in communities where people of low socioeconomic status live and work would increase access to evidence-based interventions. Research is also needed to understand the role and potential mechanisms by which factors in diet, intestinal microbiome, and/or inflammation contribute to differences in colorectal carcinogenesis. Studies of large cohorts with diverse populations are needed to identify epidemiologic and molecular factors that contribute to CRC development in different populations.

The impact of race, comorbid conditions and obesity on survival endpoints in women with high grade endometrial carcinoma.

OBJECTIVE: To estimate overall survival, disease-specific survival, and progression-free survival among high grade endometrial carcinoma cases and to determine factors impacting survival for non-Hispanic white and non-Hispanic black women. METHODS: We identified high grade endometrial carcinoma cases among non-Hispanic white and non-Hispanic black women from ongoing institutional studies, and determined eligibility through medical record and pathologic review. We estimated effects of demographic and clinical variables on survival outcomes using Kaplan Meier methods and Cox proportional hazards modelling. RESULTS: Non-Hispanic Black women with BMI <25.0 had poorest overall survival compared to non-Hispanic white women with BMI <25.0 (HR 3.03; 95% CI [1.35, 6.81]), followed by non-Hispanic black women with BMI 25.0+ (HR 2.43; 95% CI [1.28, 4.60]). A similar pattern emerged for disease-specific survival. Non-Hispanic black women also had poorer progression-free survival than non-Hispanic white women (HR 1.40; 95% CI [1.01, 1.93]). Other significant factors impacting survival outcomes included receipt of National Cancer Center Network (NCCN) guideline-concordant treatment (GCT), earlier stage at diagnosis, and fewer comorbid conditions. CONCLUSIONS: BMI and race interact and modify the association with high grade endometrial carcinoma survival. Other potentially modifiable factors, such as reducing comorbidities and increasing access to GCT will potentially improve survival after diagnosis of high grade endometrial carcinomas. A better understanding of the molecular drivers of these high grade carcinomas may lead to targeted therapies that reduce morbidity and mortality associated with these aggressive tumors.

Educating the Next Generation of Undergraduate URM Cancer Scientists: Results and Lessons Learned from a Cancer Research Partnership Scholar Program.

To improve cancer disparities among under-represented minority (URM) populations, better representation of URM individuals in cancer research is needed. The San Diego State University and University of California San Diego Moores Cancer Center Partnership is addressing cancer disparities through an educational program targeting undergraduate URM students. The Partnership provides a paid intensive summer research internship enriched with year-round activities that include educational sessions, a journal club, mentorship, social activities, and poster sessions and presentations. Program evaluation through follow-up surveys, focus groups, and other formal and informal feedback, including advisory and program steering committees, are used to improve the program. Long-term follow-up among scholars (minimum of 10 years) provides data to evaluate the program's long-term impact on scholars' education and career path. Since 2016, 63 URM undergraduate students participated in the scholar program. At the year-2 follow-up (2016 cohort; n = 12), 50% had completed their Graduate Record Examination (GRE) and/or applied to graduate or medical school. Lessons learned during the course of the program led to implementation of changes to provide a better learning experience and increase overall program satisfaction. Updates were made to recruitment timeline, improvements of the recruitment processes, refinement of the program contracts and onboarding meetings, identification of essential program coordinator skills and responsibilities, adjustments to program components, and establishment of a well-mapped and scheduled evaluation plan. The Partnership identified best practices and lessons learned for implementing lab-based internship scholar programs in biomedical and public health fields that could be considered in other programs.

Receptor tyrosine kinase recepteur d'origine nantais as predictive marker for aggressive prostate cancer in African Americans.

Published evidence shows a correlation between several molecular markers and prostate cancer (PCa) progression including in African Americans (AAs) who are disproportionately affected. Our early detection efforts led to the identification of elevated levels of antiapoptotic protein, c-FLIP and its upstream regulatory factors such as androgen receptor (AR), recepteur d'origine nantais (RON), a receptor tyrosine kinase in human prostate tumors. The primary objective of this study was to explore whether these markers play a role in racial disparities using immunohistochemistry in prostatectomy samples from a cohort of AA, Hispanic Whites (HWs), and non-Hispanic Whites (NHWs). Bivariable and multivariable logistic regression analyses were used to identify a statistical association between molecular markers, possible correlation with risk factors including race, obesity, prostate-specific antigen (PSA) and disease aggressiveness. Further, changes in the levels and expression of these molecular markers were also evaluated using human PCa cell lines. We found significantly elevated levels of RON ( P = 0.0082), AR ( P = 0.0001), c-FLIP ( P = 0.0071) in AAs compared with HWs or NHWs. Furthermore, a higher proportion of HW and NHWs had a high Gleason score (>6) but not PSA as compared to AAs ( P = 0.032). In summary, our findings suggest that PSA was important in predicting aggressive disease for the cohort overall; however, high levels of RON may play a role in predisposing AA men to develop aggressive disease. Future research is needed using large datasets to confirm these findings and to explore whether all or any of these markers could aid in race-specific stratification of patients for treatment.

Racial Disparity in Gastrointestinal Cancer Risk.

Cancer from the gastrointestinal tract and its associated excretory organs will occur in more than 300,000 Americans in 2017, with colorectal cancer responsible for >40% of that burden; there will be more than 150,000 deaths from this group of cancers in the same time period. Disparities among subgroups related to the incidence and mortality of these cancers exist. The epidemiology and risk factors associated with each cancer bear out differences for racial groups in the United States. Esophageal adenocarcinoma is more frequent in non-Hispanic whites, whereas esophageal squamous cell carcinoma with risk factors of tobacco and alcohol is more frequent among blacks. Liver cancer has been most frequent among Asian/Pacific Islanders, chiefly due to hepatitis B vertical transmission, but other racial groups show increasing rates due to hepatitis C and emergence of cirrhosis from non-alcoholic fatty liver disease. Gastric cancer incidence remains highest among Asian/Pacific Islanders likely due to gene-environment interaction. In addition to esophageal squamous cell carcinoma, cancers of the small bowel, pancreas, and colorectum show the highest rates among blacks, where the explanations for the disparity are not as obvious and are likely multifactorial, including socioeconomic and health care access, treatment, and prevention (vaccination and screening) differences, dietary and composition of the gut microbiome, as well as biologic and genetic influences. Cognizance of these disparities in gastrointestinal cancer risk, as well as approaches that apply precision medicine methods to populations with the increased risk, may reduce the observed disparities for digestive cancers.

Unraveling the etiology of ovarian cancer racial disparity in the deep south: Is it nature or nurture?

BACKGROUND: Our objective was to evaluate racial treatment and survival disparities in black women with ovarian cancer in the Deep South and to determine how environmental factors / socioeconomic status (SES) influence survival. METHODS: A retrospective study of ovarian cancer patients from 2007 to 2014 was performed. Socioeconomic status (SES) was obtained though U.S. Census block data and compared using Yost scores. Comparisons were performed using standard statistical approaches. RESULTS: A total of 393 patients were evaluated, 325 (83%) white and 68 (17%) black. Demographic information and surgical approach were similar in each racial group. However, compared to whites, black patients had lower rates of optimal debulking [89% vs. 71%, respectively (p=0.001)] and intraperitoneal chemotherapy (19% vs. 11%, p=0.01). Black women had lower SES parameters including education, income, and poverty. As a result, more black patients had the lowest SES (SES-1) when compared to white patients (17% vs. 41%, p<0.001). When controlling for these factors by cox regression analysis, a survival disadvantage was seen in black women for both progression free survival (16 vs. 27months, p=0.003) and overall survival (42 vs. 88months, p<0.001). CONCLUSIONS: Despite controlling for clinical and environmental factors, a survival disadvantage was still observed in black patients with ovarian cancer in the Deep South. Black women had lower optimal debulking rates and more platinum resistant disease. These data suggest other factors like tumor biology may play a role in racial survival differences, however, more research is needed to determine this causation.

Prevalence and Correlates of Major Depressive Symptoms among Black Men with Prostate Cancer.

Objectives: The objectives of our study were to determine the prevalence of major depressive symptoms and identify factors that are associated with major depressive symptoms among Black men with prostate cancer (PCa). Design: This study consisted of 415 Black men aged 40-81 years that entered the North Carolina Central Cancer Registry during the years 2007-2008. The primary outcome variable was depressive symptoms (CES-D). Factors included age, income, education, insurance status, treatment received, time between diagnosis and treatment, Gleason score, medical mistrust and experience with racism/discrimination. Logistic regression models were used to assess factors associated with the odds of having major depressive symptoms. Results: The prevalence of major depressive symptoms (≥16 on CES-D) among our sample of Black men with PCa was approximately 33%. Approximately 15% of the study participants underwent radiation beam treatment. Age was significantly associated with the odds of reporting major depressive symptoms (OR= .95, CI .91-.99) among Black men. In addition, compared with all other forms of treatment, Black men who underwent radiation beam treatment had higher odds (OR=2.38, CI 1.02- 5.51) of reporting major depressive symptoms. Conclusion: Nearly one-third of Black men with PCa in this study reported major depressive symptoms. Clinicians should pay closer attention to the mental health status of Black men with PCa, especially those who are younger and those who have undergone radiation beam treatment. Cancer survivorship, particularly quality of life, may be enhanced by opportunities for assessment, evaluation and intervention of depressive symptoms among these men disproportionately affected by PCa.

Comparing treatment and outcomes of ductal carcinoma in situ among women in Missouri by race.

PURPOSE: To investigate whether treatment (surgery, radiation therapy, and endocrine therapy) contributes to racial disparities in outcomes of ductal carcinoma in situ (DCIS). PATIENTS AND METHODS: The analysis included 8184 non-Hispanic White and 954 non-Hispanic Black women diagnosed with DCIS between 1996 and 2011 and identified in the Missouri Cancer Registry. Logistic regression models were used to estimate odds ratios (ORs) of treatment for race. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) of ipsilateral breast tumor (IBT) and contralateral breast tumor (CBT) for race. RESULTS: There was no significant difference between Black and White women in utilization of mastectomy (OR 1.16; 95 % CI 0.99-1.35) or endocrine therapy (OR 1.19; 95 % CI 0.94-1.51). Despite no significant difference in underutilization of radiation therapy (OR 1.14; 95 % CI 0.92-1.42), Black women had higher odds of radiation delay, defined as at least 8 weeks between surgery and radiation (OR 1.92; 95 % CI 1.55-2.37). Among 9138 patients, 184 had IBTs and 326 had CBTs. Black women had a higher risk of IBTs (HR 1.69; 95 % CI 1.15-2.50) and a comparable risk of CBTs (HR 1.19; 95 % CI 0.84-1.68), which were independent of pathological features and treatment. CONCLUSION: Racial differences in DCIS treatment and outcomes exist in Missouri. This study could not completely explain the higher risk of IBTs in Black women. Future studies should identify differences in timely initiation and completion of treatment, which may contribute to the racial difference in IBTs after DCIS.

Racial disparities in esophageal cancer survival after surgery.

OBJECTIVES: Esophageal cancer (EC) black patients have higher mortality rates than Whites. The lower rate of surgery in Blacks may explain the survival difference. We explored the Surveillance Epidemiology and End Results database to determine the impact of surgery on mortality in Blacks and Whites EC. METHODS: All cases of pathologically proven local and locoregional adenocarcinoma and squamous cell carcinoma of the esophagus from 1973 to 2011 were identified (13,678 White, 2,894 Black patients). Cervical esophageal cancer was excluded. Age, sex, diagnosis year, stage, cancer-directed surgery, radiation, and vital status were analyzed according to self-reported race. RESULTS: Blacks had higher 1-year mortality, adjusted for age, sex, stage, year of diagnosis, histology, and therapy [adjusted hazard ratio (HRadj ): 1.24 (95% CI 1.16-1.32)]. Undergoing surgery was an independent predictor of improved survival overall (HRadj 0.30, 95% CI 0.27-0.33). Black patients treated surgically experienced significantly lower survival than Whites, but the difference was not observed in those who did not undergo surgery. CONCLUSIONS: Although surgery appears to reduce mortality overall, early survival is worse for Blacks. Investigation into racial disparities in health care access and delivery, and to skilled esophageal surgeons is warranted to improve survival for all patients, particularly Blacks. J. Surg. Oncol. 2016;113:659-664. © 2016 Wiley Periodicals, Inc.

Enhancing food access in a comprehensive cancer center area of influence through local partner capacity building.

BACKGROUND: Food insecurity, an economic and social condition of limited food access, is associated with poor diet quality-a risk factor for several common cancers. The University of Texas MD Anderson Cancer Center supports healthy food access through community-led evidence translation by actively partnering with community-based organizations (CBOs). These partnerships aim to enhance the capacity of food assistance CBOs to effectively implement evidence-based food insecurity mitigation programs in the cancer center's area of influence. METHODS: This case study aims to describe the cancer center's model for local food access capacity building and detail operationalization in the context of a whole-community cancer prevention effort (Be Well Baytown) in Baytown, Texas. RESULTS: Elements central to the capacity building model include (i) assessment of baseline needs and capacity, (ii) empowering a community champion within a relevant CBO, (iii) mapping inter-sectoral community partnerships, collaborations, and linkages, and (iv) leveraging systems, connections, and resources to provide an enabling environment for overall food access systems growth. Through this process, Be Well Baytown enhanced the capacity of a local food pantry leading to increases in total reach, pounds of food distributed, and number of food distribution events in collaboration with intersectoral partners from 2018 to 2023. CONCLUSION: This case study highlights the model's implementation as a co-benefit community partnership strategy to maximize the impact of food security programs integrated with comprehensive cancer center prevention efforts.

Cancer disparities in Appalachian Kentucky.

PURPOSE: Cancer is the second leading cause of death in the United States, and the disease burden is elevated in Appalachian Kentucky, due in part to health behaviors and inequities in social determinants of health. This study's goal was to evaluate Appalachian Kentucky's cancer burden compared to non-Appalachian Kentucky, and Kentucky compared to the United States (excluding Kentucky). METHODS: The following data were analyzed: annual all-cause and all-site cancer mortality rates from 1968 to 2018; 5-year all-site and site-specific cancer incidence and mortality rates from 2014 to 2018; aggregated screening and risk factor data from 2016 to 2018 for the United States (excluding Kentucky), Kentucky, non-Appalachian Kentucky, and Appalachian Kentucky; and human papilloma virus vaccination prevalence by sex from 2018 for the United States and Kentucky. FINDINGS: Since 1968, the United States has experienced a large decrease in all-cause and cancer mortality, but the reduction in Kentucky has been smaller and slower, driven by even smaller and slower reductions within Appalachian Kentucky. Appalachian Kentucky has higher overall cancer incidence and mortality rates and higher rates for several site-specific cancers compared to non-Appalachian Kentucky. Contributing factors include screening rate disparities and increased rates of obesity and smoking. CONCLUSIONS: Appalachian Kentucky has experienced persistent cancer disparities, including elevated all-cause and cancer mortality rates for 50+ years, widening the gap between this region and the rest of the country. In addition to addressing social determinants of health, increased efforts aimed at improving health behaviors and increased access to health care resources could help reduce this disparity.

Demographic, clinical, and social characteristics of anal cancer among patients stratified by age (<50 and ≥50 years) in Alabama between 2012 and 2018.

BACKGROUND: Anal cancer is increasing globally, with a high number of new cases occurring in highly developed countries, including the U.S. The incidence of anal cancer is higher among people living with HIV (PLHIV), and the U.S. South continues to see higher HIV incidence rates and lagging HPV vaccination rates. We aimed to identify factors associated with early onset anal cancer in Alabama which may help explain cancer disparities in the South. METHODS: Using a cross-sectional study design, we examined demographic, clinical, and social characteristics among anal cancer patients stratified by diagnosis age (<50 and ≥50 years) in the Alabama cancer registry between 2012 and 2018. We used Wilcoxon rank sums and Pearson chi-square tests to assess associations between age at diagnosis, demographic (i.e., sex, race, marital status), clinical (i.e., BMI, HIV infection, site, stage, and histological type), and social (i.e. social vulnerability) characteristics, and multivariable logistic regression to estimate the odds of early onset cancer. RESULTS: Among 519 patients with anal cancer in Alabama, 92 (17.7 %) were diagnosed at <50 years. The majority of patients were female (66.5 %) and White (83.4 %). Male sex, Black race, and HIV infection were associated with younger age at diagnosis. Black patients had a 4-fold increased odds of early onset anal cancer compared to White patients (AOR=4.39, CI=1.54-12.49). Black patients disproportionately lived in areas with higher social vulnerability. About 42 % of patients in areas with the highest social vulnerability were diagnosed with stage 3 or 4 cancer. About 8 % of cases were among people aged 35-44 years, which is close to double the proportion of anal cancer cases in this age group in the U.S. (4.7 %). CONCLUSIONS: Patients who are Black, male, and PLHIV may be at higher risk of early onset anal cancer compared to other populations in the South.

A noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children.

Hispanic/Latino children have the highest risk of acute lymphoblastic leukemia (ALL) in the US compared to other racial/ethnic groups, yet the basis of this remains incompletely understood. Through genetic fine-mapping analyses, we identified a new independent childhood ALL risk signal near IKZF1 in self-reported Hispanic/Latino individuals, but not in non-Hispanic White individuals, with an effect size of ∼1.44 (95% confidence interval = 1.33-1.55) and a risk allele frequency of ∼18% in Hispanic/Latino populations and <0.5% in European populations. This risk allele was positively associated with Indigenous American ancestry, showed evidence of selection in human history, and was associated with reduced IKZF1 expression. We identified a putative causal variant in a downstream enhancer that is most active in pro-B cells and interacts with the IKZF1 promoter. This variant disrupts IKZF1 autoregulation at this enhancer and results in reduced enhancer activity in B cell progenitors. Our study reveals a genetic basis for the increased ALL risk in Hispanic/Latino children.