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Last Modified, June 28, 2020
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Mailed fecal immunochemical test outreach for colorectal cancer screening: Summary of a Centers for Disease Control and Prevention-sponsored summit

CA Cancer J Clin

2020 Jason Dominitz; Rachel Issaka

Uptake of colorectal cancer screening remains suboptimal. Mailed fecal immunochemical testing (FIT) offers promise for increasing screening rates, but optimal strategies for implementation have not been well synthesized. In June 2019, the Centers for Disease Control and Prevention convened a meeting of subject matter experts and stakeholders to answer key questions regarding mailed FIT implementation in the United States. Points of agreement included: 1) primers, such as texts, telephone calls, and printed mailings before mailed FIT, appear to contribute to effectiveness; 2) invitation letters should be brief and easy to read, and the signatory should be tailored based on setting; 3) instructions for FIT completion should be simple and address challenges that may lead to failed laboratory processing, such as notation of collection date; 4) reminders delivered to initial noncompleters should be used to increase the FIT return rate; 5) data infrastructure should identify eligible patients and track each step in the outreach process, from primer delivery through abnormal FIT follow-up; 6) protocols and procedures such as navigation should be in place to promote colonoscopy after abnormal FIT; 7) a high-quality, 1-sample FIT should be used; 8) sustainability requires a program champion and organizational support for the work, including sufficient funding and external policies (such as quality reporting requirements) to drive commitment to program investment; and 9) the cost effectiveness of mailed FIT has been established. Participants concluded that mailed FIT is an effective and efficient strategy with great potential for increasing colorectal cancer screening in diverse health care settings if more widely implemented.

We understand our community: implementation of the Healthy Eating Healthy Aging program among community-based organizations

Transl Behav Med

2020 Sonia Bishop; Linda Ko

Cardiovascular disease is the second leading cause of death in the USA among Asian Americans and Pacific Islanders (AAPIs) over the age of 65. Healthy Eating Healthy Aging (HEHA), an evidence-based heart health program, can provide culturally appropriate nutrition education to decrease the risk of cardiovascular disease. Community-based organizations (CBOs) are optimal settings to implement community-based programs. However, there is inadequate research on how evidence-based interventions like HEHA are implemented in CBOs. This study examined processes that facilitated the implementation of HEHA among CBOs serving older AAPIs. Twelve representatives from CBOs that implemented the HEHA program were recruited to participate in a semistructured interview. All the participants were CBO directors or senior managers. A semistructured interview guide was created and informed by the Consolidated Framework for Implementation Research (CFIR) to capture how HEHA played into the five domains of CFIR: (a) intervention characteristics, (b) outer setting, (c) inner setting, (d) characteristics of the individuals, and (e) process. Data analysis captured themes under the CFIR domains. All five CFIR domains emerged from the interviews. Under intervention characteristics, three constructs emerged as facilitating the implementation of HEHA: (a) the participant's beliefs around the quality of the HEHA program and its ability to promote healthy eating, (b) HEHA's adaptability to different AAPI subgroups, and (c) perceptions of how successfully HEHA was bundled and assembled. Under outer setting, the participants described the community's need for healthy eating programs and how the HEHA program meets that need. Four constructs emerged under inner setting: (a) the CBO's structural characteristics and social standing in the community; (b) resources dedicated to the implementation and ongoing operations, including funding, training, education, physical space, and time; (c) the culture of the CBO; and (d) the participant's commitment and involvement in marketing, promotion, and implementation of HEHA. Under characteristics of individuals, participants' described their desire to learn the content of HEHA and deliver them successfully. Under process, participants described strategies to engage relevant individuals to facilitate HEHA implementation. The interviews with CBO representatives provided insights into CFIR domain constructs that facilitated the implementation of HEHA. CBOs are key settings for community health education. Understanding processes that lead to the successful implementation of evidence-based interventions among CBOs is critical for accelerating the dissemination and implementation of best practices.

Use of Aspirin and Statins in Relation to Inflammation in Benign Prostate Tissue in the Placebo Arm of the Prostate Cancer Prevention Trial

Cancer Prev Res (Phila)

2020 Catherine Tangen; Phyllis Goodman; Kathryn Arnold

Aspirin and statin use may lower risk of advanced/fatal prostate cancer, possibly by reducing intraprostatic inflammation. To test this hypothesis, we investigated the association of aspirin and statin use with the presence and extent of intraprostatic inflammation, and the abundance of specific immune cell types, in benign prostate tissue from a subset of men from the placebo arm of the Prostate Cancer Prevention Trial. Men were classified as aspirin or statin users if they reported use at baseline or during the seven-year trial. Presence and extent of inflammation were assessed, and markers of specific immune cell types (CD4, CD8, FoxP3, CD68, c-KIT) were scored, in slides from end-of-study prostate biopsies taken irrespective of clinical indication, per trial protocol. Logistic regression was used to estimate associations between medication use and inflammation measures, adjusted for potential confounders. Of 357 men included, 61% reported aspirin use and 32% reported statin use. Prevalence and extent of inflammation were not associated with medication use. However, aspirin users were more likely to have low FoxP3, a T regulatory cell marker (OR: 5.60, 95% CI: 1.16-27.07), and statin users were more likely to have low CD68, a macrophage marker (OR: 1.63, 95% CI: 0.81-3.27). If confirmed, these results suggest that these medications may alter the immune milieu of the prostate, which could potentially mediate effects of these medications on advanced/fatal prostate cancer risk.

Reply to S. Boutayeb et al

JCO Oncol Pract

2020 Veena Shankaran

N/A

Urine Tenofovir Levels Measured by a Novel Immunoassay Predict HIV Protection

Clin Infect Dis

2020 Nelly Mugo; Deborah Donnell

New tools are needed to support PrEP adherence for individuals at risk for HIV, including those that enable provision of real-time feedback. In a large, completed PrEP trial, adequate urine tenofovir levels measured by a novel immunoassay predicted HIV protection and showed good sensitivity and specificity for detectable plasma tenofovir.

Associations between physical activity, sedentary behavior and urinary oxidized guanine in colorectal cancer patients: Results from the ColoCare Study

Appl Physiol Nutr Metab

2020 Christopher Li

To determine associations between physical activity (PA), sedentary behavior (SB) and oxidative stress in colorectal cancer patients, ColoCare Study participants in Germany wore an accelerometer 6- and/or 12-months post-surgery. Spearman partial correlations were used to assess associations between PA and urinary concentrations of oxidized guanine, a validated marker of oxidative stress. There were no significant associations between PA or SB and oxidized guanine in n=76 measurements (ng/mgcreatinine; r=0.03, p=0.76 for PA, r=-0.05, p=0.69 for SB). Novelty: Objectively-measured physical activity was not associated with a marker of oxidative stress in colorectal cancer patients.

The impact of COVID-19 on colorectal cancer disparities and the way forward

Gastrointest Endosc

2020 Rachel Issaka

In response to the COVID-19 pandemic, the United States Surgeon General advised all hospitals and ambulatory care centers to delay nonurgent medical procedures and surgeries. This recommendation, echoed by a multigastroenterology society guideline, led to the suspension of colonoscopies for colorectal cancer (CRC) screening and surveillance. Although this temporary suspension was necessary to contain COVID-19 infections, we as gastroenterologists, patient advocates, and CRC researchers have witnessed the downstream impact of COVID-19 and this recommendation on CRC screening, research, and advocacy. These effects are particularly noticeable in medically underserved communities where CRC morbidity and mortality are highest. COVID-19 related pauses in medical care, as well as shifts in resource allocation and workforce deployment, threaten decades worth of work to improve CRC disparities in medically underserved populations. In this perspective, we present the unique challenges COVID-19 poses to health equity in CRC prevention and provide potential solutions as we navigate these uncharted waters.

Developing and evaluating risk prediction models with panel current status data

Biometrics

2020 Yingye Zheng

Panel current status data arise frequently in biomedical studies when the occurrence of a particular clinical condition is only examined at several prescheduled visit times. Existing methods for analyzing current status data have largely focused on regression modeling based on commonly used survival models such as the proportional hazards model and the accelerated failure time model. However, these procedures have the limitations of being difficult to implement and performing sub-optimally in relatively small sample sizes. The performance of these procedures is also unclear under model mis-specification. In addition, no methods currently exist to evaluate the prediction performance of estimated risk models with panel current status data. In this paper, we propose a simple estimator under a general class of non-parametric transformation (NPT) models by fitting a logistic regression working model and demonstrate that our proposed estimator is consistent for the NPT model parameter up to a scale multiplier. Furthermore, we propose non-parametric estimators for evaluating the prediction performance of the risk score derived from model fitting, which is valid regardless of the adequacy of the fitted model. Extensive simulation results suggest that our proposed estimators perform well in finite samples and the regression parameter estimators outperform existing estimators under various scenarios. We illustrate the proposed procedures using data from the Framingham Offspring Study. This article is protected by copyright. All rights reserved.

Population-based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high-grade serous ovarian cancer

J Med Genet

2020 Mary Anne Rossing; Holly Harris

PURPOSE: The known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting that other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes. METHODS: We sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Genes with an increased frequency of putative deleterious variants in cases versus controls were further examined in an independent set of 14135 EOC cases and 28655 controls from the Ovarian Cancer Association Consortium and the UK Biobank. For each gene, we estimated the EOC risks and evaluated associations between germline variant status and clinical characteristics. RESULTS: The ORs associated for high-grade serous ovarian cancer were 3.01 for PALB2 (95%CI 1.59 to 5.68; p=0.00068), 1.99 for POLK (95%CI 1.15 to 3.43; p=0.014) and 4.07 for SLX4 (95%CI 1.34 to 12.4; p=0.013). Deleterious mutations in FBXO10 were associated with a reduced risk of disease (OR 0.27, 95%CI 0.07 to 1.00, p=0.049). However, based on the Bayes false discovery probability, only the association for PALB2 in high-grade serous ovarian cancer is likely to represent a true positive. CONCLUSIONS: We have found strong evidence that carriers of PALB2 deleterious mutations are at increased risk of high-grade serous ovarian cancer. Whether the magnitude of risk is sufficiently high to warrant the inclusion of PALB2 in cancer gene panels for ovarian cancer risk testing is unclear; much larger sample sizes will be needed to provide sufficiently precise estimates for clinical counselling.

Genome-wide gene-diabetes and gene-obesity interaction scan in 8,255 cases and 11,900 controls from the PanScan and PanC4 Consortia

Cancer Epidemiol Biomarkers Prev

2020 Ulrike Peters; Phyllis Goodman; J White; Charles Kooperberg

BACKGROUND: Obesity and diabetes are major modifiable risk factors for pancreatic cancer. Interactions between genetic variants and diabetes/obesity have not previously been comprehensively investigated in pancreatic cancer at the genome-wide level. METHODS: We conducted a gene-environment interaction (GxE) analysis including 8,255 cases and 11,900 controls from four pancreatic cancer GWAS datasets (PanScan I-III and PanC4). Obesity (BMI=30 kg/m2) and diabetes (duration = 3 years) were the environmental variables of interest. Approximately 870,000 SNPs were analyzed. Case-control (CC), case-only (CO), and joint-effect test methods were used for SNP-level GxE analysis. As a complementary approach, gene-based GxE analysis was also performed. Age, sex, study site and principal components accounting for population substructure were included as covariates. Meta-analysis was applied to combine individual-GWAS summary statistics. RESULTS: No genome-wide significant interactions with diabetes or obesity were detected at the SNP level by the CC or CO approaches. The joint-effect test detected numerous genome-wide significant GxE signals in the GWAS main effects top hit regions but the significance diminished after adjusting for the GWAS top hits. In the gene-based analysis, a significant interaction of diabetes with variants in the FAM63A (family with sequence similarity 63 member A) gene (significance threshold P<1.25E-6) was observed in the meta-analysis (PGxE= 1.2E-6, PJoint= 4.2E-7). CONCLUSIONS: Our current analyses did not find significant GxE interactions at the SNP level but found one significant interaction with diabetes at the gene level. A larger sample size might unveil additional genetic factors via GxE scans. IMPACT: This study may contribute to discovering the mechanism of diabetes-associated pancreatic cancer.