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Fifteen-year population attributable fractions and causal pies of risk factors for newly developed hepatocellular carcinomas in 11,801 men in Taiwan.

ABSTRACT: Development of hepatocellular carcinoma (HCC) is a multi-factorial process. Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are important risk factors of HCC. Host factors, such as alcohol drinking, may also play a role. This study aims to provide a synthesis view on the development of HCC by examining multiple risk factors jointly and collectively. Causal-pie modeling technique was applied to analyze a cohort of 11,801 male residents (followed up for 15 years) in Taiwan, during which a total of 298 incident HCC cases were ascertained. The rate ratios adjusted by age were further modeled by an additive Poisson regression. Population attributable fractions (PAFs) and causal-pie weights (CPWs) were calculated. A PAF indicates the magnitude of case-load reduction under a particular intervention scenario, whereas a CPW for a particular class of causal pies represents the proportion of HCC cases attributable to that class. Using PAF we observed a chance to reduce around 60% HCC risk moving from no HBV-related intervention to the total elimination of the virus. An additional ?15% (or ?5%) reduction can be expected, if the HBV-related intervention is coupled with an HCV-related intervention (or an anti-drinking campaign). Eight classes of causal pies were found to be significant, including four dose-response classes of HBV (total CPW=52.7%), one independent-effect class of HCV (CPW=14.4%), one HBV-alcohol interaction class (CPW=4.2%), one HBV-HCV interaction class (CPW=1.7%), and one all-unknown class (CPW=27.0%). Causal-pie modeling for HCC helps clarify the relative importance of each viral and host factor, as well as their interactions.

SUBMITTER: Liao SF

PROVIDER: S-EPMC3323561 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Fifteen-year population attributable fractions and causal pies of risk factors for newly developed hepatocellular carcinomas in 11,801 men in Taiwan.

Liao Shu-Fen SF Yang Hwai-I HI Lee Mei-Hsuan MH Chen Chien-Jen CJ Lee Wen-Chung WC

PloS one 20120410 4

Development of hepatocellular carcinoma (HCC) is a multi-factorial process. Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are important risk factors of HCC. Host factors, such as alcohol drinking, may also play a role. This study aims to provide a synthesis view on the development of HCC by examining multiple risk factors jointly and collectively. Causal-pie modeling technique was applied to analyze a cohort of 11,801 male residents (followed up for 15 years) in Tai ...[more]

PMID: 22506050

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Project description:Risk factors for hepatocellular carcinoma (HCC) include hepatitis B and C viruses (HBV, HCV), excessive alcohol consumption, rare genetic disorders and diabetes/obesity. The population attributable fractions (PAF) of these factors, however, have not been investigated in population-based studies in the United States.Persons ?68 years diagnosed with HCC (n=6,991) between 1994 and 2007 were identified in the SEER-Medicare database. A 5% random sample (n=255,702) of persons residing in SEER locations were selected for comparison. For each risk factor, odds ratios (ORs), 95% confidence intervals (95% CI) and PAFs were calculated.As anticipated, the risk of HCC was increased in relationship to each factor: HCV (OR 39.89, 95% CI: 36.29-43.84), HBV (OR 11.17, 95% CI: 9.18-13.59), alcohol-related disorders (OR 4.06, 95% CI: 3.82-4.32), rare metabolic disorders (OR 3.45, 95% CI: 2.97-4.02), and diabetes and/or obesity (OR 2.47, 95% CI: 2.34-2.61). The PAF of all factors combined was 64.5% (males 65.6%; females 62.2%). The PAF was highest among Asians (70.1%) and lowest among black persons (52.4%). Among individual factors, diabetes/obesity had the greatest PAF (36.6%), followed by alcohol-related disorders (23.5%), HCV (22.4%), HBV (6.3%) and rare genetic disorders (3.2%). While diabetes/obesity had the greatest PAF among both males (36.4%) and females (36.7%), alcohol-related disorders had the second greatest PAF among males (27.8%) and HCV the second greatest among females (28.1%). Diabetes/obesity had the greatest PAF among whites (38.9%) and Hispanics (38.1%), while HCV had the greatest PAF among Asians (35.4%) and blacks (34.9%). The second greatest PAF was alcohol-related disorders in whites (25.6%), Hispanics (30.1%) and blacks (and 18.5%) and HBV in Asians (28.5%).The dominant risk factors for HCC in the United States among persons ?68 years differ by sex and race/ethnicity. Overall, eliminating diabetes/obesity could reduce the incidence of HCC more than the elimination of any other factor.

Project description:BackgroundAsymptomatic carriage of malaria parasites is common in high transmission intensity areas and confounds clinical case definitions for research studies. This is important for investigations that aim to identify immune correlates of protection from clinical malaria. The proportion of fevers attributable to malaria parasites is widely used to define different thresholds of parasite density associated with febrile episodes. The varying intensity of malaria transmission was investigated to check whether it had a significant impact on the parasite density thresholds. The same dataset was used to explore an alternative statistical approach, using the probability of developing fevers as a choice over threshold cut-offs. The former has been reported to increase predictive power.MethodsData from children monitored longitudinally between 2005 and 2017 from Junju and Chonyi in Kilifi, Kenya were used. Performance comparison of Bayesian-latent class and logistic power models in estimating malaria attributable fractions and probabilities of having fever given a parasite density with changing malaria transmission intensity was done using Junju cohort. Zero-inflated beta regressions were used to assess the impact of using probabilities to evaluate anti-merozoite antibodies as correlates of protection, compared with multilevel binary regression using data from Chonyi and Junju.ResultsMalaria transmission intensity declined from over 49% to 5% between 2006 and 2017, respectively. During this period, malaria attributable fraction varied between 27-59% using logistic regression compared to 10-36% with the Bayesian latent class approach. Both models estimated similar patterns of fevers attributable to malaria with changing transmission intensities. The Bayesian latent class model performed well in estimating the probabilities of having fever, while the latter was efficient in determining the parasite density threshold. However, compared to the logistic power model, the Bayesian algorithm yielded lower estimates for both attributable fractions and probabilities of fever. In modelling the association of merozoite antibodies and clinical malaria, both approaches resulted in comparable estimates, but the utilization of probabilities had a better statistical fit.ConclusionsMalaria attributable fractions, varied with an overall decline in the malaria transmission intensity in this setting but did not significantly impact the outcomes of analyses aimed at identifying immune correlates of protection. These data confirm the statistical advantage of using probabilities over binary data.

Project description:BackgroundAs the cannabis-cancer relationship remains an important open question epidemiological investigation is warranted to calculate key metrics including Rate Ratios (RR), Attributable Fractions in the Exposed (AFE) and Population Attributable Risks (PAR) to directly compare the implicated case burden between emerging cannabinoids and the established carcinogen tobacco.MethodsSEER*Stat software from Centres for Disease Control was used to access age-standardized state census incidence of 28 cancer types (including "All (non-skin) Cancer") from National Cancer Institute in US states 2001-2017. Drug exposures taken from the National Survey of Drug Use and Health 2003-2017, response rate 74.1%. Federal seizure data provided cannabinoid exposure. US Census Bureau furnished income and ethnicity. Exposure dichotomized as highest v. lowest exposure quintiles. Data processed in R.ResultsNineteen thousand eight hundred seventy-seven age-standardized cancer rates were returned. Based on these rates and state populations this equated to 51,623,922 cancer cases over an aggregated population 2003-2017 of 124,896,418,350. Fifteen cancers displayed elevated E-Values in the highest compared to the lowest quintiles of cannabidiol exposure, namely (in order): prostate, melanoma, Kaposi sarcoma, ovarian, bladder, colorectal, stomach, Hodgkins, esophagus, Non-Hodgkins lymphoma, All cancer, brain, lung, CLL and breast. Eleven cancers were elevated in the highest THC exposure quintile: melanoma, thyroid, liver, AML, ALL, pancreas, myeloma, CML, breast, oropharynx and stomach. Twelve cancers were elevated in the highest tobacco quintile confirming extant knowledge and study methodology. For cannabidiol RR declined from 1.397 (95%C.I. 1.392, 1.402), AFE declined from 28.40% (28.14, 28.66%), PAR declined from 15.3% (15.1, 15.5%) and minimum E-Values declined from 2.13. For THC RR declined from 2.166 (95%C.I. 2.153, 2.180), AFE declined from 53.8% (53.5, 54.1%); PAR declined from 36.1% (35.9, 36.4%) and minimum E-Values declined from 3.72. For tobacco, THC and cannabidiol based on AFE this implies an excess of 93,860, 91,677 and 48,510 cases; based on PAR data imply an excess of 36,450, 55,780 and 14,819 cases.ConclusionData implicate 23/28 cancers as being linked with THC or cannabidiol exposure with epidemiologically-causal relationships comparable to those for tobacco. AFE-attributable cases for cannabinoids (91,677 and 48,510) compare with PAR-attributable cases for tobacco (36,450). Cannabinoids constitute an important multivalent community carcinogen.

Project description:BACKGROUND: The development of microarray technology has greatly enhanced our ability to evaluate gene expression. In theory, the expression of all genes in a given organism can be monitored simultaneously. Sequencing of the chicken genome has provided the crucial information for the design of a comprehensive chicken transcriptome microarray. A long oligonucleotide microarray has been manually curated and designed by our group and manufactured using Agilent inkjet technology. This provides a flexible and powerful platform with high sensitivity and specificity for gene expression studies. RESULTS: A chicken 60-mer oligonucleotide microarray consisting of 42,034 features including the entire Marek's disease virus, two avian influenza virus (H5N2 and H5N3), and 150 chicken microRNAs has been designed and tested. In an important validation study, total RNA isolated from four major chicken tissues: cecal tonsil (C), ileum (I), liver (L), and spleen (S) were used for comparative hybridizations. More than 95% of spots had high signal noise ratio (SNR > 10). There were 2886, 2660, 358, 3208, 3355, and 3710 genes differentially expressed between liver and spleen, spleen and cecal tonsil, cecal tonsil and ileum, liver and cecal tonsil, liver and ileum, spleen and ileum (P < 10-7), respectively. There were a number of tissue-selective genes for cecal tonsil, ileum, liver, and spleen identified (95, 71, 535, and 108, respectively; P < 10-7). Another highlight of these data revealed that the antimicrobial peptides GAL1, GAL2, GAL6 and GAL7 were highly expressed in the spleen compared to other tissues tested. CONCLUSION: A chicken 60-mer oligonucleotide 44K microarray was designed and validated in a comprehensive survey of gene expression in diverse tissues. The results of these tissue expression analyses have demonstrated that this microarray has high specificity and sensitivity, and will be a useful tool for chicken functional genomics. Novel data on the expression of putative tissue specific genes and antimicrobial peptides is highlighted as part of this comprehensive microarray validation study. The information for accessing and ordering this 44K chicken array can be found at http://people.tamu.edu/~hjzhou/TAMUAgilent44KArray/

Dataset Information

Fifteen-year population attributable fractions and causal pies of risk factors for newly developed hepatocellular carcinomas in 11,801 men in Taiwan.

Publications

Fifteen-year population attributable fractions and causal pies of risk factors for newly developed hepatocellular carcinomas in 11,801 men in Taiwan.

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