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Understanding patterns of shared and type-specific etiologies for colorectal polyps may provide insights into colorectal carcinogenesis. The authors present the first systematic comparison of risk factors by colorectal polyp type in a large colonoscopy-based case-control study of 3,764 polyp-free controls and 2,543 polyp patients, including 1,444 cases with adenomas only, 662 cases with hyperplastic polyps (HPPs) only, and 437 cases with synchronous HPPs and adenomas. Surveys were completed to obtain information on usual dietary intake and other lifestyle factors. Six lifestyle factors, including cigarette smoking, obesity, no regular use of nonsteroidal anti-inflammatory drugs, high intake of red meat, low intake of fiber, and low intake of calcium, were found to be independently associated with the risk of polyps. The risk of polyps increased progressively with an increasing number of adverse lifestyle factors. Compared with participants with no or only 1 risk factor, odds ratios for those with 5 to 6 risk factors were 2.72 (95% confidence interval: 1.94, 3.79) for adenoma only, 4.12 (95% confidence interval: 2.78, 6.09) for HPPs only, and 9.03 (95% confidence interval: 5.69, 14.34) for synchronous HPPs and adenomas. This study provides strong evidence that lifestyle modification is important for the prevention of colorectal polyps, especially advanced and multiple adenomas, which are established precursors of colorectal cancer. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: To identify factors associated with diagnostic delay after an incomplete or abnormal mammogram among women participating in a state mammography screening program.Research Approach: Retrospective case-control design using bivariate and multivariate logistic regression analyses to explore the associations between age, race, ethnicity, marital status, breast cancer history, and self-reported breast symptoms and delay.Setting: A statewide program of free screening mammography for women who are under- or uninsured.Participants: 11,460 women enrolled in a free, statewide screening program from 2002-2006.Methodologic Approach: Using the Tennessee Breast and Cervical Cancer Screening Program database, further analyses were conducted.Main Research Variables: The outcome measure was delay in completion of all diagnostic tests and was defined as women who did not complete testing within 60 days.Findings: Thirty-seven percent of women required follow-up, and of a subset used in the analysis, 30% experienced delay of more than 60 days. Controlling for marital status, age, and breast cancer history, women who experienced delay were more likely to be African American versus Caucasian (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.13, 1.85) or Hispanic (OR = 0.72, 95% CI = 0.55, 0.93) and to have self-reported breast symptoms (OR = 1.50, 95% CI = 1.27, 1.77).Conclusions: In a sample of women with low income needing mammography follow-up, delay was associated with three intrapersonal variables, potentially reducing the effectiveness of mammography screening for women who were African American, or Hispanic, or had self-reported breast symptoms.Interpretation: Nurses providing cancer screening examinations are uniquely positioned to assess the knowledge, beliefs, and resources of women using the program and to navigate women through barriers to completion. Knowledge of factors associated with delay is valuable for planning interventions and allocating program resources. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) is a common and morbid complication of left heart disease with 2 subtypes: isolated post-capillary pulmonary hypertension (Ipc-PH) and combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH). Little is known about the clinical or physiological characteristics that distinguish these 2 subphenotypes or if Cpc-PH shares molecular similarities to pulmonary arterial hypertension (PAH).Objectives: The goal of this study was to test the hypothesis that the hemodynamic and genetic profile of Cpc-PH would more closely resemble PAH than Ipc-PH.Methods: Vanderbilt University's electronic medical record linked to a DNA biorepository was used to extract demographic characteristics, clinical data, invasive hemodynamic data, echocardiography, and vital status for all patients referred for right heart catheterization between 1998 and 2014. Shared genetic variants between PAH and Cpc-PH compared with Ipc-PH were identified by using pre-existing single-nucleotide polymorphism data.Results: A total of 2,817 patients with PH (13% Cpc-PH, 52% Ipc-PH, and 20% PAH) were identified. Patients with Cpc-PH were on average 6 years younger, with more severe pulmonary vascular disease than patients with Ipc-PH, despite similar comorbidities and prevalence, severity, and chronicity of left heart disease. After adjusting for relevant covariates, the risk of death was similar between the Cpc-PH and Ipc-PH groups (hazard ratio: 1.14; 95% confidence interval: 0.96 to 1.35; p = 0.15) when defined according to diastolic pressure gradient. We identified 75 shared exonic single-nucleotide polymorphisms between Cpc-PH and PAH enriched in pathways involving cell structure, extracellular matrix, and immune function. These genes are expressed, on average, 32% higher in lungs relative to other tissues.Conclusions: Patients with Cpc-PH develop pulmonary vascular disease similar to patients with PAH, despite younger age and similar prevalence of obesity, diabetes mellitus, and left heart disease compared with patients with Ipc-PH. An exploratory genetic analysis in Cpc-PH identified genes and biological pathways in the lung known to contribute to PAH pathophysiology, suggesting that Cpc-PH may be a distinct and highly morbid PH subphenotype. [ABSTRACT FROM AUTHOR]

Importance: Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2)., Objective: To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer., Design, Setting, and Participants: This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228 patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease., Exposures: Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19., Main Outcomes and Measures: The primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching., Results: After exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42)., Conclusions and Relevance: Findings from this cohort study suggest that ADT use was not associated with decreased mortality from SARS-CoV-2 infection. However, large ongoing clinical trials will provide further evidence on the role of ADT or other androgen-targeted therapies in reducing COVID-19 infection severity.

Despite available demographic data on the factors that contribute to breast cancer mortality in large population datasets, local patterns are often overlooked. Such local information could provide a valuable metric by which regional community health resources can be allocated to reduce breast cancer mortality. We used national and statewide datasets to assess geographical distribution of breast cancer mortality rates and known risk factors influencing breast cancer mortality in middle Tennessee. Each county in middle Tennessee, and each ZIP code within metropolitan Davidson County, was scored for risk factor prevalence and assigned quartile scores that were used as a metric to identify geographic areas of need. While breast cancer mortality often correlated with age and incidence, geographic areas were identified in which breast cancer mortality rates did not correlate with age and incidence, but correlated with additional risk factors, such as mammography screening and socioeconomic status. Geographical variability in specific risk factors was evident, demonstrating the utility of this approach to identify local areas of risk. This method revealed local patterns in breast cancer mortality that might otherwise be overlooked in a more broadly based analysis. Our data suggest that understanding the geographic distribution of breast cancer mortality, and the distribution of risk factors that contribute to breast cancer mortality, will not only identify communities with the greatest need of support, but will identify the types of resources that would provide the most benefit to reduce breast cancer mortality in the community.

Many phytochemicals in fruits and vegetables have been shown to have cancer-inhibitory effects in animal studies. These effects on cancer, however, have not been clearly demonstrated in human studies. This study investigated the association between fruit and vegetable intakes and the risk of adenomatous polyps. Participants were part of the Tennessee Colorectal Polyp Study. Eligible participants aged 40-75 y were recruited from patients undergoing colonoscopy at 2 medical centers in Nashville, Tennessee from 2003 to 2005. Cases had at least one adenoma and controls were polyp free. Dietary intake was assessed using a self-administered FFQ. Associations between dietary intakes and adenoma risk were evaluated using unconditional logistic regression with restricted cubic function spline. In multivariate analyses of 764 cases and 1517 controls, increased intakes of total fruits, berries, fruit juice, and green leafy vegetables were associated with reduced adenoma risk. The odds ratio for upper tertile intake compared with lower was 0.66 (95% CI = 0.51-0.86) for total fruits, 0.64 (95% CI = 0.47-0.87) for berries, 0.72 (95% CI = 0.56-0.92) for fruit juice, and 0.74 (95% CI = 0.58-0.96) for green vegetables. This study provides additional evidence that high total fruit intake and certain fruit and vegetable intakes may be associated with a reduced risk of colorectal adenomas.

Background/purpose: We questioned whether primary surgical correction of neonatally diagnosed Hirschsprung's Disease (HD) incurs higher costs or increased incidence of adverse events (AE) when compared with staged repair., Methods: We reviewed the medical records of all neonates diagnosed with HD at our institution between 1997 and 2007. Sixty subjects fulfilled criteria for inclusion. Twenty-seven neonates had primary repair, and 33 had staged repair. We measured inflation-adjusted total costs, direct costs, and total charges and 6 AE between the 2 groups. A generalized linear model was used to examine differences between group variables., Results: We found no statistically significant difference in costs or AE between primary and staged repair. Inflation-adjusted median financial data for primary or staged repair were, respectively, as follows: total costs, $35,670 vs $38,538 (P = .617); direct costs, $18,453 vs $23,937 (P = .128); total charges, $107,315 vs $102,492 (P = .690). Adverse events occurred in 48% of primary repair subjects and 36% of staged repair subjects (P = .434); no single AE differed significantly between the two groups., Conclusions: We found no statistical evidence that primary neonatal correction of HD adds cost or risk of AE when compared with a traditional staged approach in neonates who met inclusion criteria.

The authors evaluated alcohol drinking and cigarette smoking in relation to risk of colorectal polyps in a Nashville, Tennessee, colonoscopy-based case-control study. In 2003-2005, cases with adenomatous polyps only (n = 639), hyperplastic polyps only (n = 294), and both types of polyps (n = 235) were compared with 1,773 polyp-free controls. Unordered polytomous logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals. Consumption of at least five alcoholic drinks per week was not strongly associated with development of polyps. Odds ratios for all polyp types were increased for dose, duration, and pack-years of cigarette smoking and were stronger for hyperplastic polyps than for adenoma. Compared with never smoking, dose-response relations were particularly strong for current smoking and duration; for > or =35 years of smoking, odds ratios were 1.9 (95% confidence interval (CI): 1.4, 2.5) for adenomatous polyps only, 5.0 (95% CI: 3.3, 7.3) for hyperplastic polyps only, and 6.9 (95% CI: 4.4, 11.1) for both types of polyps. Compared with current smoking, time since cessation was associated with substantially reduced odds; for > or =20 years since quitting, odds ratios were 0.4 (95% CI: 0.3, 0.6) for adenoma only, 0.2 (95% CI: 0.1, 0.3) for hyperplastic polyps only, and 0.2 (95% CI: 0.2, 0.4) for both polyp types. These findings support the adverse role of cigarette smoking in colorectal tumorigenesis and suggest that quitting smoking may substantially reduce the risk of colorectal polyps.

Most colorectal cancers arise from adenomatous polyps or certain hyperplastic polyps. Only a few studies have investigated potential genetic modifiers of the associations between meat intake and polyp risk, and results are inconsistent. Using data from the Tennessee Colorectal Polyp Study, a large colonoscopy-based study, including 1,002 polyp cases (557 adenoma only, 250 hyperplastic polyp only, 195 both polyps) and 1,493 polyp-free patients, we evaluated the association of colorectal polyp risk with carcinogen exposure from meat and genetic polymorphisms in enzymes involved in heterocyclic amine (HCA) metabolism, including N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2), cytochrome P450 1A2 (CYP1A2), and aryl hydrocarbon receptor (AhR). Data on intake levels of meats by preparation methods, doneness preferences, and other lifestyle factors were obtained. Fourteen single nucleotide polymorphisms in the AhR, CYP1A2, NAT1, and NAT2 genes were evaluated. No clear association was found for any polymorphisms with polyp risk. However, apparent interactions were found for intake of meat and HCAs with AhR, NAT1, and NAT2 genotypes, and the interactions were statistically significant for the group with both adenomatous and hyperplastic polyps. Dose-response relationships with meat or HCA intake were found only among those with the AhR GA/AA (rs2066853) genotype, NAT1 rapid, or NAT2 rapid/intermediate acetylators but not among those with other genotypes of these genes. This dose-response relationship was more evident among those with both AhR GA/AA and the NAT1 rapid acetylator than those without this genotype combination. These results provide strong evidence for a modifying effect of metabolizing genes on the association of meat intake and HCA exposure with colorectal polyp risk.

Although meat intake has been fairly consistently linked to the risk of colorectal cancer, only a few studies have evaluated meat intake by doneness level and the heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) produced by high temperature cooking of meat in relation to colorectal adenomatous and hyperplastic polyps. We evaluated these associations in a large colonoscopy-based case-control study. Included in this study were participants with adenomatous polyp only (n = 573), hyperplastic polyp only (n = 256), or both adenomatous and hyperplastic polyps (n = 199), and 1,544 polyp-free controls. In addition to information related to demographic and other lifestyle factors, meat intake by cooking method and doneness preference were obtained through telephone interviews. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals for the association between exposures and colorectal polyp risks. Presence of hyperplastic polyp was found to be positively associated with high consumption of total meat (p(trend) = 0.076) or red meat (p(trend) = 0.060), with an approximate 50-60% elevated risk observed in the highest vs. the lowest intake group. High intake of 2-amino-I-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,4,8-trimethylimidazo [4,5]quinoxaline (DiMeIQx) were associated with increased risk for hyperplastic polyp (p(trend) = 0.036 and 0.038, respectively). With a possible exception of the intake of total well-done meats (p(trend) = 0.055) or well-done red meats (p(trend) = 0.074) with the risk of large adenomas, no other positive association was found specifically for the risk of adenomas with any of the exposure variables aforementioned. This study provides additional support for a positive association of high intake of red meat with colorectal adenomas, and suggests that high intake of meats and meat carcinogens may also be associated with hyperplastic polyps.

Background: It remains unknown whether nonsteroidal anti-inflammatory drugs (NSAIDs) confer a protective effect against lung cancer development. We examined the relationship between NSAID exposure and subsequent lung cancer development in a large statewide, population-based cohort., Design: Nested case-control study in the Tennessee Medicaid population from 1990 to 2000., Methods: Lung cancer cases were identified using a statewide computerized claims database. Each time a case was identified, age- and sex-matched controls were randomly selected from the available source population. A detailed pharmacy database quantified nonsteroidal anti-inflammatory drug (NSAID) exposure during the 5 years before cancer diagnosis, and conditional logistic regression was used to examine the relationship between NSAID exposure and lung cancer development. Identical analyses were repeated in a subpopulation of high-risk individuals with chronic obstructive pulmonary disease (COPD)., Results: 303,399 persons were enrolled in the study population. During 1.9 million person-years of follow-up (median 6.3 years per person), 3,370 lung cancer cases were identified. Among those ever using NSAIDs, the adjusted odds ratio of developing lung cancer was 1.03 (95% confidence interval: 0.94-1.12). Among those using >24 months of NSAIDs in the 5 years before lung cancer diagnosis, the adjusted odds ratio for lung cancer was 0.96 (95% confidence interval: 0.82-1.11), and no protective effect was demonstrated in any NSAID exposure stratum. Similarly, among the 2519 high-risk individuals with chronic obstructive pulmonary disease, no significant protective effect from NSAIDs was noted., Conclusion: This large statewide, population-based study did not demonstrate a protective effect of NSAIDs on lung cancer development in either the general or high-risk chronic obstructive pulmonary disease populations.

Black women have the highest mortality for breast cancer. Our hypothesis is that racial disparities in breast cancer survival persist after controlling for stage of disease and treatment at both a city hospital as well as at a university hospital. Data from tumor registries of breast cancer patients at a city hospital and a university center were analyzed for overall and disease-specific survival, controlling for stage and treatment. Black patients presented with more advanced stages and had significantly worse survival compared with whites. After controlling for stage of disease and treatment, a difference in survival persisted for stage II patients, with blacks doing worse than whites at both institutions. Although there were socioeconomic differences, race was an independent prognostic factor, with black patients having the worse prognosis. The lower survival of black women with breast cancer is only partially explained by their advanced stage at diagnosis. Black women with potentially curable stage II cancer had a lower survival that is not explained by the variables measured.