An open-access database of infectious disease transmission trees to explore superspreader epidemiology.

Historically, emerging and reemerging infectious diseases have caused large, deadly, and expensive multinational outbreaks. Often outbreak investigations aim to identify who infected whom by reconstructing the outbreak transmission tree, which visualizes transmission between individuals as a network with nodes representing individuals and branches representing transmission from person to person. We compiled a database, called OutbreakTrees, of 382 published, standardized transmission trees consisting of 16 directly transmitted diseases ranging in size from 2 to 286 cases. For each tree and disease, we calculated several key statistics, such as tree size, average number of secondary infections, the dispersion parameter, and the proportion of cases considered superspreaders, and examined how these statistics varied over the course of each outbreak and under different assumptions about the completeness of outbreak investigations. We demonstrated the potential utility of the database through 2 short analyses addressing questions about superspreader epidemiology for a variety of diseases, including Coronavirus Disease 2019 (COVID-19). First, we found that our transmission trees were consistent with theory predicting that intermediate dispersion parameters give rise to the highest proportion of cases causing superspreading events. Additionally, we investigated patterns in how superspreaders are infected. Across trees with more than 1 superspreader, we found preliminary support for the theory that superspreaders generate other superspreaders. In sum, our findings put the role of superspreading in COVID-19 transmission in perspective with that of other diseases and suggest an approach to further research regarding the generation of superspreaders. These data have been made openly available to encourage reuse and further scientific inquiry.

Real-Time Use of a Dynamic Model To Measure the Impact of Public Health Interventions on Measles Outbreak Size and Duration - Chicago, Illinois, 2024.

Measles is a highly infectious, vaccine-preventable disease that can cause severe illness, hospitalization, and death. A measles outbreak associated with a migrant shelter in Chicago occurred during February-April 2024, in which a total of 57 confirmed cases were identified, including 52 among shelter residents, three among staff members, and two among community members with a known link to the shelter. CDC simulated a measles outbreak among shelter residents using a dynamic disease model, updated in real time as additional cases were identified, to produce outbreak forecasts and assess the impact of public health interventions. As of April 8, the model forecasted a median final outbreak size of 58 cases (IQR = 56-60 cases); model fit and prediction range improved as more case data became available. Counterfactual analysis of different intervention scenarios demonstrated the importance of early deployment of public health interventions in Chicago, with a 69% chance of an outbreak of 100 or more cases had there been no mass vaccination or active case-finding compared with only a 1% chance when those interventions were deployed. This analysis highlights the value of using real-time, dynamic models to aid public health response, set expectations about outbreak size and duration, and quantify the impact of interventions. The model shows that prompt mass vaccination and active case-finding likely substantially reduced the chance of a large (100 or more cases) outbreak in Chicago.

Association between tuberculosis in men and social network structure in Kampala, Uganda.

BACKGROUND: Globally, tuberculosis disease (TB) is more common among males than females. Recent research proposes that differences in social mixing by sex could alter infection patterns in TB. We examine evidence for two mechanisms by which social-mixing could increase men's contact rates with TB cases. First, men could be positioned in social networks such that they contact more people or social groups. Second, preferential mixing by sex could prime men to have more exposure to TB cases. METHODS: We compared the networks of male and female TB cases and healthy matched controls living in Kampala, Uganda. Specifically, we estimated their positions in social networks (network distance to TB cases, degree, betweenness, and closeness) and assortativity patterns (mixing with adult men, women, and children inside and outside the household). RESULTS: The observed network consisted of 11,840 individuals. There were few differences in estimates of node position by sex. We found distinct mixing patterns by sex and TB disease status including that TB cases have proportionally more adult male contacts and fewer contacts with children. CONCLUSIONS: This analysis used a network approach to study how social mixing patterns are associated with TB disease. Understanding these mechanisms may have implications for designing targeted intervention strategies in high-burden populations.

Texas Has the Highest Hepatocellular Carcinoma Incidence Rates in the USA.

BACKGROUND: Texas is the second largest state by area and population in the USA and is reported to have high incidence and mortality rates for hepatocellular carcinoma (HCC). The reasons for the increasingly high burden of HCC in Texas are not clear. AIMS: We explored trends and demographic and regional variations in HCC incidence to better understand reasons for the high burden in Texas. METHODS: We analyzed Texas Cancer Registry incidence data from 2001 to 2015 and compared results to the U.S. National Program of Cancer Registries and SEER for the same period. Rates were stratified by sex, race/ethnicity, and age at diagnosis. Rates were also compared between the US/Mexico border region of Texas and the rest of Texas. RESULTS: Texas had the highest HCC age-adjusted incidence rate of all states, 13.2/100,000, which was 45% higher than the national average. In Texas and nationally, rates increased by 4% per year between 2001 and 2015. Rates in Texas were 26-37% greater than national rates for Hispanics, African-Americans, and non-Hispanic whites. Among Hispanics in states with the largest percentage of Hispanics, Texas-based Hispanics had the highest HCC incidence rate in 2015 (21.2/100,000) compared with Hispanics in New Mexico, California, Arizona, Nevada, and Florida. Incidence rates were highest in South Texas and US/Mexico border regions. CONCLUSIONS: Increasing rates in the large Hispanic population may explain why Texas now has the highest HCC incidence rate in the USA.

The Burden of Elders: Anxiety, Depression, and Personal Networks in Two African Slums.

ABSTRACT: Although anxiety and depression have been central topics for scholars and clinicians in the United States, few studies have examined their correlates in sub-Saharan Africa and none have examined large urban slums. Using face-to-face interviews in two African cities, we analyze self-reported symptoms of anxiety and depression in a community-based sample (n = 495). Ordinary least squares regression was used to analyze a variety of demographic and social predictors including sex, child-rearing, marital status, education, income, age, and neighborhood for residents of Agbogbloshie (Accra, Ghana) and Kangemi (Nairobi, Kenya). Controlling for other factors, two personal network dimensions were significant. Total network size is positively associated with symptoms of anxiety and depression in Kenya but not in Ghana. However, one factor was predictive of symptoms of anxiety and depression in both locations: the reported percentage of ties with older persons. Higher levels of anxiety and depression are associated with a larger share of older individuals in one's personal network.

The statistics of epidemic transitions.

Emerging and re-emerging pathogens exhibit very complex dynamics, are hard to model and difficult to predict. Their dynamics might appear intractable. However, new statistical approaches-rooted in dynamical systems and the theory of stochastic processes-have yielded insight into the dynamics of emerging and re-emerging pathogens. We argue that these approaches may lead to new methods for predicting epidemics. This perspective views pathogen emergence and re-emergence as a "critical transition," and uses the concept of noisy dynamic bifurcation to understand the relationship between the system observables and the distance to this transition. Because the system dynamics exhibit characteristic fluctuations in response to perturbations for a system in the vicinity of a critical point, we propose this information may be harnessed to develop early warning signals. Specifically, the motion of perturbations slows as the system approaches the transition.

Rural-urban differences in health behaviors and outcomes among older, overweight, long-term cancer survivors in the RENEW randomized control trial.

PURPOSE: Rural cancer survivors (RCS) have poorer health outcomes and face multiple challenges-older age, and limited transportation, education, income, and healthcare access. Yet, RCS are understudied. The Reach-out to ENhancE Wellness(RENEW) trial, a home-based, diet and exercise intervention among 641 breast, prostate, and colorectal cancer survivors addressed many of these challenges. METHODS: We examined whether rural and urban participants differed in their response to the RENEW intervention (e.g., physical functioning, quality-of-life, intakes of fruits and vegetables (F&V) and saturated fat, body mass index(BMI), physical activity, and adverse events). RESULTS: Rural versus urban survivors report significantly more favorable mean (SE) changes in physical functioning [- 0.66 (1.47) v - 1.71 (1.00)], physical health [+ 0.14 (0.71) v - 0.74 (0.50)], and fewer adverse events [1.58 (0.08) v 1.64 (0.06)]. Rural versus urban survivors reported smaller increases in F&Vs [+ 1.47 (0.23) v + 1.56(0.16); p = 0.018], and lower percentages achieved goal behavior for endurance exercise and intakes of F&Vs and saturated fat. CONCLUSIONS: The RENEW intervention reduced declines in physical health and functioning among RCS to a significantly greater extent than for urban cancer survivors. All survivors significantly improved intakes of F&V and saturated fat, and endurance exercise; however, lower percentages of rural versus urban survivors met goal suggesting that more intensive interventions may be needed for RCS.

Anticipating epidemic transitions with imperfect data.

Epidemic transitions are an important feature of infectious disease systems. As the transmissibility of a pathogen increases, the dynamics of disease spread shifts from limited stuttering chains of transmission to potentially large scale outbreaks. One proposed method to anticipate this transition are early-warning signals (EWS), summary statistics which undergo characteristic changes as the transition is approached. Although theoretically predicted, their mathematical basis does not take into account the nature of epidemiological data, which are typically aggregated into periodic case reports and subject to reporting error. The viability of EWS for epidemic transitions therefore remains uncertain. Here we demonstrate that most EWS can predict emergence even when calculated from imperfect data. We quantify performance using the area under the curve (AUC) statistic, a measure of how well an EWS distinguishes between numerical simulations of an emerging disease and one which is stationary. Values of the AUC statistic are compared across a range of different reporting scenarios. We find that different EWS respond to imperfect data differently. The mean, variance and first differenced variance all perform well unless reporting error is highly overdispersed. The autocorrelation, autocovariance and decay time perform well provided that the aggregation period of the data is larger than the serial interval and reporting error is not highly overdispersed. The coefficient of variation, skewness and kurtosis are found to be unreliable indicators of emergence. Overall, we find that seven of ten EWS considered perform well for most realistic reporting scenarios. We conclude that imperfect epidemiological data is not a barrier to using EWS for many potentially emerging diseases.

Forecasting infectious disease emergence subject to seasonal forcing.

BACKGROUND: Despite high vaccination coverage, many childhood infections pose a growing threat to human populations. Accurate disease forecasting would be of tremendous value to public health. Forecasting disease emergence using early warning signals (EWS) is possible in non-seasonal models of infectious diseases. Here, we assessed whether EWS also anticipate disease emergence in seasonal models. METHODS: We simulated the dynamics of an immunizing infectious pathogen approaching the tipping point to disease endemicity. To explore the effect of seasonality on the reliability of early warning statistics, we varied the amplitude of fluctuations around the average transmission. We proposed and analyzed two new early warning signals based on the wavelet spectrum. We measured the reliability of the early warning signals depending on the strength of their trend preceding the tipping point and then calculated the Area Under the Curve (AUC) statistic. RESULTS: Early warning signals were reliable when disease transmission was subject to seasonal forcing. Wavelet-based early warning signals were as reliable as other conventional early warning signals. We found that removing seasonal trends, prior to analysis, did not improve early warning statistics uniformly. CONCLUSIONS: Early warning signals anticipate the onset of critical transitions for infectious diseases which are subject to seasonal forcing. Wavelet-based early warning statistics can also be used to forecast infectious disease.

Effects of Brief Messaging About Undiagnosed Infections Detected through HIV Testing Among Black and Latino Men Who Have Sex With Men in the United States.

We examined intent to get tested for HIV infection and use condoms among n = 604 uninfected black and Latino men who have sex with men after receiving brief information messaging that 1 in 10 minority men who have sex with men had HIV infection and did not know it. Information awareness, newness, believability, HIV testing cost willingness, and associated demographic variables were also assessed.

Multivitamin-mineral use is associated with reduced risk of cardiovascular disease mortality among women in the United States.

BACKGROUND: Multivitamin-mineral (MVM) products are the most commonly used supplements in the United States, followed by multivitamin (MV) products. Two randomized clinical trials (RCTs) did not show an effect of MVMs or MVs on cardiovascular disease (CVD) mortality; however, no clinical trial data are available for women with MVM supplement use and CVD mortality. OBJECTIVE: The objective of this research was to examine the association between MVM and MV use and CVD-specific mortality among US adults without CVD. METHODS: A nationally representative sample of adults from the restricted data NHANES III (1988-1994; n = 8678; age ≥40 y) were matched with mortality data reported by the National Death Index through 2011 to examine associations between MVM and MV use and CVD mortality by using Cox proportional hazards models, adjusting for multiple potential confounders. RESULTS: We observed no significant association between CVD mortality and users of MVMs or MVs compared with nonusers; however, when users were classified by the reported length of time products were used, a significant association was found with MVM use of >3 y compared with nonusers (HR: 0.65; 95% CI: 0.49, 0.85). This finding was largely driven by the significant association among women (HR: 0.56; 95% CI: 0.37, 0.85) but not men (HR: 0.79; 95% CI: 0.44, 1.42). No significant association was observed for MV products and CVD mortality in fully adjusted models. CONCLUSIONS: In this nationally representative data set with detailed information on supplement use and CVD mortality data ∼20 y later, we found an association between MVM use of >3 y and reduced CVD mortality risk for women when models controlled for age, race, education, body mass index, alcohol, aspirin use, serum lipids, blood pressure, and blood glucose/glycated hemoglobin. Our results are consistent with the 1 available RCT in men, indicating no relation with MVM use and CVD mortality.

Combining genome-wide methods to investigate the genetic complexity of courtship song variation in Drosophila melanogaster.

Little is currently known about the genetic complexity of quantitative behavioral variation, the types of genes involved, or their effects on intermediate phenotypes. Here, we conduct a genome-wide association study of Drosophila melanogaster courtship song variation using 168 sequenced inbred lines, and fail to find highly significant associations. However, by combining these data with results from a well-powered Evolve and Resequence (E&R) study on the same trait, we provide statistical evidence that some power to associate genotype and phenotype is available. Genes that are significant in both analyses are enriched for expression in the nervous system, and affect neural development and synaptic growth when perturbed. Quantitative complementation at one of these loci, Syntrophin-like 1, supports a hypothesis that variation at this locus affects variation in the inter-pulse interval of courtship song. These results suggest that experimental evolution may provide an approach for genome-scale replication in Drosophila.

Daughters and Mothers Against Breast Cancer (DAMES): main outcomes of a randomized controlled trial of weight loss in overweight mothers with breast cancer and their overweight daughters.

BACKGROUND: Few studies to date have used the cancer diagnosis as a teachable moment to promote healthy behavior changes in survivors of cancer and their family members. Given the role of obesity in the primary and tertiary prevention of breast cancer, the authors explored the feasibility of a mother-daughter weight loss intervention. METHODS: A randomized controlled trial of a mailed weight loss intervention was undertaken among 68 mother-daughter dyads (n = 136), each comprised of a survivor of breast cancer (AJCC stage 0-III) and her adult biological daughter. All women had body mass indices ≥ 25 kg/m(2) and underwent in-person assessments at baseline, 6 months, and 12 months, with accelerometry and exercise capacity performed on a subset of individuals. All women received a personalized workbook and 6 newsletters over a 1-year period that promoted weight loss; exercise; and a nutrient-rich, low-energy density diet. A total of 25 dyads received individually tailored instruction (individual), 25 dyads received team-tailored instruction (TEAM), and 18 dyads received standardized brochures (control). RESULTS: The trial met its accrual target, experienced 90% retention, and caused no serious adverse events. Significant differences in baseline to 12-month changes were observed between individual versus control mothers for body mass index, weight, and waist circumference (WC); significant differences also were observed in the WC of corresponding daughters (P < .05). Significant differences were found between individual versus control and team versus control dyads for WC (P = .0002 and .018, respectively), minutes per week of physical activity (P = .031 and .036, respectively), and exercise capacity (P = .047 for both). CONCLUSIONS: Significant improvements in lifestyle behaviors and health outcomes are possible with tailored print interventions directed toward survivors of cancer and their family members. For greater impact, more research is needed to expand this work beyond the mother-daughter dyad.

Higher diet quality is associated with decreased risk of all-cause, cardiovascular disease, and cancer mortality among older adults.

Increased attention in dietary research and guidance has been focused on dietary patterns, rather than on single nutrients or food groups, because dietary components are consumed in combination and correlated with one another. However, the collective body of research on the topic has been hampered by the lack of consistency in methods used. We examined the relationships between 4 indices--the Healthy Eating Index-2010 (HEI-2010), the Alternative Healthy Eating Index-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH)--and all-cause, cardiovascular disease (CVD), and cancer mortality in the NIH-AARP Diet and Health Study (n = 492,823). Data from a 124-item food-frequency questionnaire were used to calculate scores; adjusted HRs and 95% CIs were estimated. We documented 86,419 deaths, including 23,502 CVD- and 29,415 cancer-specific deaths, during 15 y of follow-up. Higher index scores were associated with a 12-28% decreased risk of all-cause, CVD, and cancer mortality. Specifically, comparing the highest with the lowest quintile scores, adjusted HRs for all-cause mortality for men were as follows: HEI-2010 HR: 0.78 (95% CI: 0.76, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.78), aMED HR: 0.77 (95% CI: 0.75, 0.79), and DASH HR: 0.83 (95% CI: 0.80, 0.85); for women, these were HEI-2010 HR: 0.77 (95% CI: 0.74, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.79), aMED HR: 0.76 (95% CI: 0.73, 0.79), and DASH HR: 0.78 (95% CI: 0.75, 0.81). Similarly, high adherence on each index was protective for CVD and cancer mortality examined separately. These findings indicate that multiple scores reflect core tenets of a healthy diet that may lower the risk of mortality outcomes, including federal guidance as operationalized in the HEI-2010, Harvard's Healthy Eating Plate as captured in the AHEI-2010, a Mediterranean diet as adapted in an Americanized aMED, and the DASH Eating Plan as included in the DASH score.

Effects of whey protein and resistance exercise on body composition: a meta-analysis of randomized controlled trials.

OBJECTIVES: The objective of the present meta-analysis was to examine the effect of whey protein (WP), with or without resistance exercise, on body weight and body composition in randomized controlled trials (RCTs) conducted in generally healthy adult study populations. METHODS: A comprehensive literature search was conducted to identify RCTs that investigated WP (concentrate, isolate, or hydrolystate) and body weight, body mass index (BMI), body fat, lean body mass (LBM), fat-free mass (FFM), and waist circumference. Random effects meta-analyses were conducted to generate weighted group mean differences (WGMD) for between-group comparisons (WP vs other protein sources or carbohydrates) and within-WP group comparisons (i.e., differences from baseline to trial end). Studies were classified into 2 distinct groups-WP as a supplement without dietary modification (WPS) and WP as a replacement for other sources of calories (WPR)-and were meta-analyzed separately. Subgroup analyses included examining the effect of resistance exercise and type of WP on the relationship between WP and body composition. RESULTS: Fourteen RCTs were included, with a total of 626 adult study completers. Five studies examined the effects of WPR and the remaining 9 studies examined the effects of WPS. Body weight (WGMD: -4.20 kg, 95% confidence interval [CI], -7.67, -0.73) and body fat (WGMD: -3.74 kg, 95% CI, -5.98, -1.50) were significantly decreased from baseline in the WPR within-group analyses. In the between-group analyses, the effects of WP were more favorable when compared with carbohydrates than protein sources other than whey, although findings did not reach statistical significance. Results from the subgroup analyses indicated a statistically significant increase in LBM (WGMD: 2.24 kg, 95% CI, 0.66, 3.81) among studies that included a resistance exercise component along with WP provision. CONCLUSION: The current body of literature supports the use of WP, either as a supplement combined with resistance exercise or as part of a weight loss or weight maintenance diet, to improve body composition parameters.

Perceived and objective diet quality in US adults: a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES).

OBJECTIVE: The Dietary Approaches to Stop Hypertension (DASH) dietary pattern has been shown to reduce cardiometabolic risk. Little is understood about the relationship between objective diet quality and perceived diet quality (PDQ), a potential psychosocial barrier to appropriate dietary intake. We compared PDQ and diet quality measured by a nutrient-based DASH index score in the USA. DESIGN: Cross-sectional study. Participants in the 2005-2006 National Health and Nutrition Examination Survey (NHANES) rated diet quality on a 5-point Likert scale and PDQ scores were generated (low, medium, high). A single 24 h dietary recall was used to estimate DASH index scores (range 0-9 points) by assigning 0, 0·5 or 1 point (optimal) for nine target nutrients: total fat, saturated fat, protein, cholesterol, fibre, Ca, Mg, K and Na. SETTING: Nationally representative sample of the US population. SUBJECTS: Adults aged ≥19 years in 2005-2006 NHANES (n 4419). RESULTS: Participants with high PDQ (33 %) had higher DASH index scores (mean 3·0 (sd 0·07)) than those with low PDQ (mean 2·5 (sd 0·06), P < 0·001), but average scores did not align with targets for intermediate or optimal DASH accordance. Adults with high PDQ reported higher total fat, saturated fat and Na intakes compared with optimal DASH nutrient goals. Differences between those with high v. low PDQ were similar for Whites and Blacks, but there was no difference between PDQ groups for Mexican Americans. CONCLUSIONS: Among Whites and Blacks, but not Mexican Americans, high PDQ may be associated with higher diet quality, but not necessarily a diet meeting DASH nutrient goals. This disconnect between PDQ and actual diet quality may serve as a target in obesity prevention.

Cost savings of reduced constipation rates attributed to increased dietary fiber intakes: a decision-analytic model.

BACKGROUND: Nearly five percent of Americans suffer from functional constipation, many of whom may benefit from increasing dietary fiber consumption. The annual constipation-related healthcare cost savings associated with increasing intakes may be considerable but have not been examined previously. The objective of the present study was to estimate the economic impact of increased dietary fiber consumption on direct medical costs associated with constipation. METHODS: Literature searches were conducted to identify nationally representative input parameters for the U.S. population, which included prevalence of functional constipation; current dietary fiber intakes; proportion of the population meeting recommended intakes; and the percentage that would be expected to respond, in terms of alleviation of constipation, to a change in dietary fiber consumption. A dose-response analysis of published data was conducted to estimate the percent reduction in constipation prevalence per 1 g/day increase in dietary fiber intake. Annual direct medical costs for constipation were derived from the literature and updated to U.S. $ 2012. Sensitivity analyses explored the impact on adult vs. pediatric populations and the robustness of the model to each input parameter. RESULTS: The base case direct medical cost-savings was $12.7 billion annually among adults. The base case assumed that 3% of men and 6% of women currently met recommended dietary fiber intakes; each 1 g/day increase in dietary fiber intake would lead to a reduction of 1.9% in constipation prevalence; and all adults would increase their dietary fiber intake to recommended levels (mean increase of 9 g/day). Sensitivity analyses, which explored numerous alternatives, found that even if only 50% of the adult population increased dietary fiber intake by 3 g/day, annual medical costs savings exceeded $2 billion. All plausible scenarios resulted in cost savings of at least $1 billion. CONCLUSIONS: Increasing dietary fiber consumption is associated with considerable cost savings, potentially exceeding $12 billion, which is a conservative estimate given the exclusion of lost productivity costs in the model. The finding that $12.7 billion in direct medical costs of constipation could be averted through simple, realistic changes in dietary practices is promising and highlights the need for strategies to increase dietary fiber intakes.

Association of dietary and supplemental folate intake and polymorphisms in three FOCM pathway genes with colorectal cancer in a population-based case-control study.

Previous research has shown that greater intakes of dietary folate are associated with reduced risk for colorectal cancer (CRC) and that single nucleotide polymorphisms (SNPs) in genes involved in folate-mediated one-carbon metabolism (FOCM) also may be involved in altering CRC risk. The objective of this study was to evaluate the role of folate intake (and intakes of related dietary components such as methionine), 35 SNPs in three FOCM pathway genes (MTHFD1, MTHFR, and TYMS), and their interactions on CRC risk in a population-based case-control study in Pennsylvania (686 cases, 740 controls). Diet and supplement use was assessed for the year before diagnosis or interview for cases and controls, respectively, with a modified Diet History Questionnaire from the National Cancer Institute. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. Using a dominant model for the variant allele, several SNPs were significantly associated with CRC including MTHFD1 rs8003379 (OR = 1.65; 95% CI = 1.00-2.73) and rs17824591 (OR = 1.98; 95% CI = 1.14-3.41) and the TYMS rs2853533 SNP (OR = 1.38; 95% CI = 1.05-1.80). Using a nondominant model, the AA genotype for MTHFR rs1476413 exhibited a marginally significant (OR = 1.56; 95% CI = 1.00-2.44) association with CRC. Two TYMS SNPs (rs16948305 and rs495139) exhibited significant (P = 0.024 and P = 0.040, respectively) gene-diet interactions with folate intake. One MTHFD1 (P = 0.019) and one MTHFR (P = 0.042) SNP exhibited gene-diet interactions with methionine intake. These findings suggest that allelic variants in genes involved in FOCM interact with dietary factors including folate and methionine to modify risk for CRC.

Real-world use of antiretroviral therapy and risk of cancer among people with HIV in Texas.

BACKGROUND: Combination antiretroviral therapy (cART) may reduce cancer risk among people with HIV (PWH), but cancer-specific associations are incompletely understood. METHODS: We linked HIV and cancer registries in Texas to a national prescription claims database. cART use was quantified as the proportion of days covered (PDC). Cox proportional hazards models assessed associations of cancer risk with cART usage, adjusting for demographic characteristics, AIDS status, and time since HIV report. RESULTS: We evaluated 63 694 PWH followed for 276 804 person-years. The median cART PDC was 21.4% (interquartile range: 0.0-59.8%). cART use was associated with reduced risk of Kaposi sarcoma [adjusted hazard ratio (aHR) 0.48, 95% confidence interval (CI) 0.34-0.68 relative to unexposed status] and non-Hodgkin lymphoma (aHR 0.41, 95% CI 0.31-0.53), liver cancer (aHR 0.61, 95% CI 0.39-0.96), anal cancer (aHR 0.65, 95% CI 0.46-0.92), and a miscellaneous group of 'other' cancers (aHR 0.80, 95% CI 0.66-0.98). In contrast, cART-exposed status was not associated with risk for cervical, lung, colorectal, prostate or breast cancers. CONCLUSION: In a large HIV cohort incorporating data from prescription claims, cART was associated with greatly reduced risks of Kaposi sarcoma and non-Hodgkin lymphoma, and to a lesser degree, reduced risks of liver and anal cancers. These associations likely reflect the beneficial effects of HIV suppression and improved immune control of oncogenic viruses. Efforts to increase cART use and adherence may further decrease cancer incidence among PWH.

Cancers with epidemiologic signatures of viral oncogenicity among immunocompromised populations in the United States.

BACKGROUND: Immunosuppressed individuals have elevated risk of virus-related cancers. Identifying cancers with elevated risk in people with HIV (PWH) and solid organ transplant recipients (SOTRs), two immunosuppressed populations, may help identify novel etiologic relationships with infectious agents. METHODS: We utilized two linkages of population-based cancer registries with HIV and transplant registries in the United States. Cancer entities were systematically classified based on site and histology codes. Standardized incidence ratios (SIRs) were used to compare risk in PWH and SOTRs with the general population. For selected cancer entities, incidence rate ratios (IRRs) were calculated for indicators of immunosuppression within each population. FINDINGS: We identified 38,047 cancer cases in SOTRs and 53,592 in PWH, yielding overall SIRs of 1.66 (95%CI = 1.65-1.68) and 1.49 (95%CI = 1.47-1.50), respectively. Forty-three cancer entities met selection criteria, including conjunctival squamous cell carcinoma (SCC) (PWH SIR = 7.1, 95%CI = 5.5-9.2; SOTRs SIR = 9.4; 95%CI = 6.8-12.6). Sebaceous adenocarcinoma was elevated in SOTRs (SIR = 16.2; 95%CI = 14.0-18.6) and, among SOTRs, associated with greater risk in lung/heart transplant recipients compared to recipients of other organs (IRR = 2.3; 95%CI = 1.7-3.2). Salivary gland tumors, malignant fibrous histiocytoma (MFH), and intrahepatic cholangiocarcinoma showed elevated risk in SOTRs (SIR = 3.9; SIR = 4.7; and SIR = 3.2, respectively) but not in PWH. However, risks for these cancers were elevated following an AIDS diagnosis among PWH (IRR = 2.4; IRR = 4.3; and IRR = 2.0, respectively). INTERPRETATION: Elevated SIRs among SOTRs and PWH, and associations with immunosuppression within these populations, suggest novel infectious causes for several cancers including conjunctival SCC, sebaceous adenocarcinoma, salivary gland tumors, MFH, and intrahepatic cholangiocarcinoma.