Statin use and risk of hepatocellular carcinoma in a U.S. population

PurposeStatins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are medications widely prescribed to reduce cholesterol levels. Observational studies in high-risk populations, mostly in Asia, have suggested that statins are associated with a reduced risk of hepatocellular carcinoma (HCC). The current study sought to evaluate the association of statin use and HCC in a U.S.-based, low-risk, general population.MethodsA nested case–control study was conducted among members of the Health Alliance Plan HMO of the Henry Ford Health System enrolled between 1999 and 2010. Electronic pharmacy records of statin use were compared among tumor registry-confirmed cases of HCC (n = 94) and controls (n = 468) matched on age, sex, diagnosis date, and length of HMO enrolment.ResultsIn multivariate analyses, ever-use of statins was significantly inversely associated with development of HCC (Odds ratio (OR): 0.32, 95%CI: 0.15–0.67). No clear dose–response relationship was evident as statin use for <2 years (OR = 0.32, 95%CI = 0.13–0.83) and >2 years (OR = 0.31, 95CI% = 0.12–9.81) resulted in very similar ORs.ConclusionsThe use of statins among populations in low-risk HCC areas may be associated with decreased risk of HCC.     

Socioeconomic status,human papillomavirus,and overall survival in head and neck squamous cell carcinomas in Toronto,Canada

BackgroundDespite universal healthcare in some countries, lower socioeconomic status (SES) has been associated with worse cancer survival. The influence of SES on head and neck cancer (HNC) survival is of immense interest, since SES is associated with the risk and prognostic factors associated with this disease.Patients and methodsNewly diagnosed HNC patients from 2003 to 2010 (n = 2124) were identified at Toronto’s Princess Margaret Cancer Centre. Principal component analysis was used to calculate a composite score using neighbourhood-level SES variables obtained from the 2006 Canada Census. Associations of SES with overall survival were evaluated in HNC subsets and by p16 status (surrogate for human papillomavirus).ResultsSES score was higher for oral cavity (n = 423) and p16-positive oropharyngeal cancer (OPC, n = 404) patients compared with other disease sites. Lower SES was associated with worse survival [HR 1.14 (1.06–1.22), p = 0.0002], larger tumor staging (p < 0.001), current smoking (p < 0.0001), heavier alcohol consumption (p < 0.0001), and greater comorbidity (p < 0.0002), but not with treatment regimen (p > 0.20). After adjusting for age, sex, and stage, the lowest SES quintile was associated with the worst survival only for OPC patients [HR 1.66 (1.09–2.53), n = 832], primarily in the p16-negative subset [HR 1.63 (0.96–2.79)]. The predictive ability of the prognostic models improved when smoking/alcohol was added to the model (c-index 0.71 vs. 0.69), but addition of SES did not (c-index 0.69).ConclusionSES was associated with survival, but this effect was lost after accounting for other factors (age, sex, TNM stage, smoking/alcohol). Lower SES was associated with greater smoking, alcohol consumption, comorbidity, and stage.     

Association of DLC1 gene polymorphism with susceptibility to hepatocellular carcinoma in Chinese hepatitis B virus carriers

Background: Lost or downexpression of the gene deleted in liver cancer 1 (DLC1) has been implicated in the development of hepatocellular carcinoma (HCC). We examined the relationship between DLC1 polymorphisms and HCC risk among Chinese. Methods: Three DLC1 polymorphisms, Ex11 + 255T > G (rs3739298), Ex11-620G > A (rs532841) and IVS19 + 108C > T (rs621554), were genotyped in 434 patients with HCC and 480 controls by PCR-RFLP. The associations with the susceptibility to HCC were evaluated while controlling for confounding factors. Results: We observed significantly increased susceptibility to HCC for the C/C genotype compared with T/T of IVS19 + 108C > T in the HBV carriers (OR = 2.95, 95% CI, 1.65–5.26, P < 0.001). Compared with the haplotype G-A-T (in order of Ex11 + 255T > G, Ex11-620G > A and IVS19 + 108C > T), the haplotype T-G-C was also significantly associated with an increased susceptibility to HCC among HBV carriers (OR = 2.16, 95% CI, 1.08–4.35, P = 0.009). The stratified analysis indicated no modification of the confounding factors on the increased susceptibility to HCC related to the DLC1 polymorphism/haplotype. Conclusions: Our findings suggest that DLC1 genetic polymorphism or haplotype play a role in mediating the susceptibility to HBV-related HCC.     

Cancer incidence in the AGRICAN cohort study (2005–2011)

BackgroundNumerous studies have been conducted among farmers, but very few of them have involved large prospective cohorts, and few have included a significant proportion of women and farm workers. Our aim was to compare cancer incidence in the cohort (overall, by sex, and by work on farm, occupational status and pesticide use) within the general population.MethodsMore than 180,000 participants in the AGRICAN cohort were matched to cancer registries to identify cancer cases diagnosed from enrolment (2005–2007) to 31st December 2011. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (95%CIs).ResultsOver the period, 11,067 incident cancer cases were identified (7304 men and 3763 women). Overall cancer incidence did not differ between the cohort and the general population. Moreover, SIRs were significantly higher for prostate cancer (SIR = 1.07, 95%CI 1.03–1.11) and non-Hodgkin lymphoma (SIR = 1.09, 95%CI 1.01–1.18) among men, skin melanoma among women (SIR = 1.23, 95%CI 1.05–1.43) and multiple myeloma (men: SIR = 1.38, 95%CI 1.18–1.62; women: SIR = 1.26, 95%CI 1.02–1.54). In contrast, SIRs were lower for upper aerodigestive tract and respiratory cancers. Increase in risk was greater in male farm workers for prostate and lip cancer, in female farm workers for skin melanoma, and in male farm owners for multiple myeloma. Moreover, incidence of multiple myeloma and skin melanoma was higher among male and female pesticide users respectively.ConclusionWe found a decreased incidence for tobacco-related cancers and an increased incidence of prostate cancers, skin melanoma and multiple myeloma. Specific subgroups had a higher cancer incidence related to occupational status and pesticide use.     

Survival of hepatocellular carcinoma patients is significantly improving: a population-based study from southern Switzerland

BackgroundDuring the last 20 years, relevant diagnostic procedures and advanced treatments have been progressively introduced in the management of hepatocellular carcinoma (HCC).The aim of the present study was to assess up-to-date survival trends for HCC in southern Switzerland, a region with one of the highest incidence rates in the country.MethodsHCCs diagnosed in 1996–2009 were selected by the Ticino Cancer Registry. Cancer-specific survival (CSS) analysis was performed using the Kaplan–Meier method by calendar period: 1996–2000, 2001–2005 and 2006–2009. The log-rank test was used to detect differences in survival curves. Simultaneous assessment of prognostic factors was performed by a multivariate analysis using the Cox proportional-hazards regression model.Results619 HCCs were analysed. There was a significant increase of patients undergoing transarterial chemoembolisation (TACE), whereas patients undergoing curative or palliative supportive treatments remained unchanged (p < 0.0001). No shift to earlier stages was detected. Significant differences in CCS were observed by age-group (p < 0.0001), diagnosis period (p < 0.0001), diagnosis technique (p = 0.0035), Barcelona-Clinic liver cancer stage (p < 0.0001), treatment (p < 0.0001). Multivariate analysis confirmed the independent impact on CSS of factors above mentioned, not including the diagnosis technique. Death risk was higher for patients diagnosed in 1996–2000 (HR: 1.32; 95% CI: 1.03; 1.68) and 2001–2005 (HR: 1.33; 95% CI: 1.05; 1.67) in comparison with 2006–2009 (reference group).ConclusionsThe current population-based report describes a major increase in HCC survival. Simultaneously an increased use of TACE has been detected, probable cofactor of the observed survival increase. Possibly additional efforts could be made to decrease the HCC stage at diagnosis through active surveillance of cirrhotic patients to allow an increase in curative treatments. For sure efforts should be made to comply with a standardised staging system for HCC, particularly for comparative population-based issues.     

A potentially functional polymorphism in the promoter region of let-7 family is associated with survival of hepatocellular carcinoma

Background: The let-7 family plays a vital role in the normal cellular activity of liver cells and the carcinogenesis of hepatocellular carcinoma (HCC). In the previous study, we have detected the association between single nucleotide polymorphisms (SNPs) in the promoter region of let-7 and susceptibility to HCC. However, it is still unknown whether these polymorphisms are associated with HCC prognosis. Methods: We investigated the effect of two potentially functional SNPs in the promoter region of let-7 family, rs10877887 (T > C) and rs13293512 (T > C), on the overall survival of 331 HCC patients. Log-rank test and Cox proportional hazard models were used for the survival analyses. Results: We found that HCC patients carrying the C allele of rs10877887 had a significantly increased death risk (adjusted HR = 1.22, 95%CI = 1.02–1.47, P = 0.03 in the additive model), compared to those with T allele. In the stratified analysis, the risk effect was evident in HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage B (adjusted HR = 1.24, 95%CI = 1.02–1.51, P = 0.03) and in those who received chemotherapy or intervention (adjusted HR = 1.25, 95%CI = 1.02–1.53, P = 0.04). Conclusions: Our results suggest that rs10877887 in the promoter region of let-7 may be a prognostic biomarker for HCC patients, which need the validation from other larger studies in different populations.     

Occupational exposure to hexavalent chromium and cancers of the gastrointestinal tract: A meta-analysis

Introduction: We conducted a systematic literature review and meta-analysis of oral cavity, esophageal, stomach, small intestine, colon, and rectal cancers among workers occupationally exposed to Cr(VI). Methods: Using PubMed, studies published from 1950 to 2009 evaluating the relationship between Cr(VI) exposure and GI cancers were identified. Measures of effect and variability were extracted from 32 studies meeting specific inclusion criteria, and meta-analysis summary relative risk measures were calculated using random effects models and inverse variance weighting methods. Results: Meta-standardized mortality ratios (SMRs) were, for cancer of the: oral cavity [1.02 (95% CI = 0.77–1.34)]; esophagus [1.17 (95% CI = 0.90–1.51)]; stomach [1.09 (95% CI = 0.93–1.28)]; colon [0.89 (95% CI = 0.70–1.12)]; and rectum [1.17 (95% CI = 0.98–1.39)]. Analyses of more highly exposed subgroups included in the studies or subgroups based on geographic region or by industry with recognized Cr(VI) exposures (welding, chrome plating, chromate production, and pigment production) did not result in elevated meta-SMRs except for esophageal cancer among US cohorts [meta-SMR = 1.49 (95% CI = 1.06–2.09)]. However, that finding was based on a subgroup of only four studies, one of which was a PMR study. Potential confounding by socioeconomic status (SES), diet and/or smoking, or limitations due to the healthy-worker effect (HWE) were evaluated, and while smoking, diet and SES may be important factors that may have upwardly biased the meta-SMRs, HWE is not likely to have significantly affected the summary results. None of three studies reporting small intestine cancers observed a statistically significant increased risk. Discussion: These meta-analyses and literature review indicate that Cr(VI)-exposed workers are not at a greater risk of GI cancers than the general population.     

Cancer incidence in the Western Australian mining industry (1996–2013)

BackgroundMiners are frequently exposed to established and potential carcinogens. We aimed to assess cancer incidence in miners relative to the general population and identify high-risk subgroups.MethodsIncident cancers in Western Australian miners (n = 153,922; 86% male) during 1996–2013 were identified. Indirectly standardised incidence ratios (SIRs) were calculated and mixed-effects Poisson models were used to calculate Incidence Rate Ratios (IRRs) to identify high-risk within-cohort subgroups.ResultsCompared with the general population, the overall cancer incidence in miners (n = 4194 cases) was lower for both females (SIR:0.83, 95%CI:0.74–0.92) and males (SIR:0.96, 95%CI:0.93–0.99). Overall, cancer incidence did not differ by employment duration or employment commencement time. Ever-underground work was associated with lung cancer (IRR:1.81, 95%CI:1.11–2.93). Relative to multi-ore miners, IRRs for specific cancers were significantly different when exclusively mining: iron (prostate:0.73, 95%CI:0.56–0.94); gold (lung:1.77, 95%CI:1.04–3.01 and colorectum:1.70, 95%CI:1.16–2.51); and other metals (urinary tract:1.85, 95%CI:1.03–3.31 and leukaemia:0.36, 95%CI:0.14–0.96).ConclusionWorking underground emerged as a significant determinant of lung cancer risk in our contemporary mining cohort. Increased risks of lung, prostate, colorectal and urinary tract cancers and leukaemia were identified in miners of specific ores. These findings underline the importance of continued surveillance of the health and exposures of this relatively young cohort of miners.     

MicroRNA-224 upregulation and AKT activation synergistically predict poor prognosis in patients with hepatocellular carcinoma

Background and aimPrevious evidence has shown that microRNA (miR)-224 may function as an onco-miRNA in hepatocellular carcinoma (HCC) cells by activating AKT signaling. However, little is known about the clinical significance of the combined expression of miR-224 and phosphorylated-AKT (pAKT) on human HCC. The aim of this study was to investigate the synergistical influence of miR-224 and pAKT on clinical characteristics and prognosis in patients with HCC.MethodsOne-hundred and thirty HCC patients who had undergone curative liver resection were selected. In situ hybridization and immunohistochemistry were respectively performed to detect the expression of miR-224 and pAKT in the respective tumors.ResultsCompared with the adjacent nonneoplastic liver tissues, the expression levels of miR-224 and pAKT protein in HCC tissues were both significantly increased (both P < 0.001). In addition, the combined upregulation of miR-224 and pAKT protein was significantly associated with serum AFP (P = 0.01), tumor stage (P = 0.002) and tumor grade (P = 0.008). Moreover, HCC patients highly expressing both miR-224 and pAKT protein had worse 5-year disease-free survival and 5-year overall survival (both P < 0.001). Furthermore, the Cox proportional hazards model showed that the combined upregulation of miR-224 and pAKT protein (miR-224-high/pAKT-high) may be independent poor prognostic factors for both 5-year disease-free survival (P = 0.008) and 5-year overall survival (P = 0.01) in HCC.ConclusionThese results indicate for the first time that miR-224 upregulation and AKT activation may synergistically associate with tumor progression of HCC. The combined high expression of miR-224 and pAKT may be a potential indicator for predicting unfavorable prognosis in HCC patients.     

Geometric morphometric analysis of giant honeybee (Apis dorsata Fabricius, 1793) populations in Thailand

Geometric morphometry was used to characterize 73 Apis dorsata colonies collected from 31 different localities in five major geographic regions of mainland Thailand. We measured 19 easily identified landmarks from the digitized images of the right forewing of 10 worker bees from each colony (730 bees in total); thus, avoiding the confounding variation from haploid or diploid males. After plotting the factor scores, A. dorsata from (mainland) Thailand were found to belong to a single group, which was further supported by a hierarchical cluster analysis-generated dendrogram. Multivariate analysis of variance (MANOVA, α = 0.05) demonstrated no significant differences among the five geographic groups of A. dorsata in Thailand, producing a low degree of accuracy (31.2%) in the identification of the geographic region from which any individual bee originated. Additionally, when the bee samples were classified into two groups, those north and south of the Isthmus of Kra were not significantly different (MANOVA, α = 0.05), and a low rate of correct classification in a cross-validation test (65% correct) was found. Therefore, this geometric morphometric based analysis of worker bee wing venation pattern suggests that A. dorsata populations in mainland Thailand are panmictic.     

Symmetry of the face in old age reflects childhood social status

The association of socioeconomic status (SES) with a range of lifecourse outcomes is robust, but the causes of these associations are not well understood. Research on the developmental origins of health and disease has led to the hypothesis that early developmental disturbance might permanently affect the lifecourse, accounting for some of the burden of chronic diseases such as coronary heart disease. Here we assessed developmental disturbance using bodily and facial symmetry and examined its association with socioeconomic status (SES) in childhood, and attained status at midlife. Symmetry was measured at ages 83 (facial symmetry) and 87 (bodily symmetry) in a sample of 292 individuals from the Lothian Birth Cohort 1921 (LBC1921). Structural equation models indicated that poorer SES during early development was significantly associated with lower facial symmetry (standardized path coefficient ?.25, p = .03). By contrast, midlife SES was not significantly associated with symmetry. The relationship was stronger in men (?.44, p = .03) than in women (?.12, p = .37), and the effect sizes were significantly different in magnitude (p = .004). These findings suggest that SES in early life (but not later in life) is associated with developmental disturbances. Facial symmetry appears to provide an effective record of early perturbations, whereas bodily symmetry seems relatively imperturbable. As bodily and facial symmetries were sensitive to different influences, they should not be treated as interchangeable. However, markers of childhood disturbance remain many decades later, suggesting that early development may account in part for associations between SES and health through the lifecourse. Future research should clarify which elements of the environment cause these perturbations.     

CEP131 indicates poor prognosis and promotes cell proliferation and migration in hepatocellular carcinoma

Centrosomal proteins have been implicated in the progression of human diseases. CEP131 plays important roles in centrosome duplication and genome stability, but its role in cancers remains largely unknown. Here, we showed that CEP131 expression was increased in hepatocellular carcinoma (HCC), compared to the paracarcinoma tissues, at both mRNA and protein levels. High CEP131 expression was closely associated with tumor size (P = 0.020), tumor capsule (P = 0.043), TNM stage (P = 0.007) and tumor differentiation (P = 0.019). Furthermore, patients with high expression of CEP131 were accompanied with worse overall and disease-free survivals in our and TCGA cohorts consisting of a total of 802 cases. The prognostic value of CEP131 was further confirmed by stratified survival analysis. Multivariate cox regression model indicated that CEP131 was an independent factor for overall survival (hazard ratio = 1.762, 95% confident interval: 1.443–2.151, P < 0.001). In vitro data demonstrated that nucleophosmin (NPM) physically bound to CEP131 and maintained its protein stability. Overexpression of CEP131 in HCC cell lines enhanced cell proliferation and migration, whereas the knockdown of CEP131 led to the opposite phenotypes. Further studies demonstrated that CEP131 exhibited oncogenic activity via activation of PI3K/AKT signaling pathway. Taken together, our findings suggest CEP131 serves as a potential prognostic biomarker in HCC, and functions as an oncogene in this deadly disease.     

G-308A TNF-α polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: Case-control study

Background: Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine that may act as an endogenous tumor promoter. A genetic polymorphism of TNF-α gene at position ?308 promoter region is involved in the regulation of expression level and has been found to be associated with susceptibility to various types of cancer. Methods: To determine the association of the TNF-α gene G-308A polymorphism on the risk of hepatocellular carcinoma (HCC) in a Turkish population, a hospital-based case-control study was designed consisting of 110 diagnosis subjects with hepatocellular carcinoma and 110 cancer-free control subjects matched on age, gender, smoking and alcohol status. The genotype frequency of this polymorphism was determined by using a polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay. Results: The distribution G-308A genotype was significantly associated with the risk of HCC (p < 0.001, odds ratio [OR] = 4.75, 95% confidence interval [CI] = 2.25–9.82 for ?308 AA/GA genotypes versus GG genotype). Conclusion: We suggested that the presence of the high producer allele ?308A in the TNF-α gene appears to be associated with an increased risk for the development of HCC in Turkish population.     

Incidence,survival and mortality rates of stage-specific bladder cancer in United States: A trend analysis

PurposeTo examine the overall and stage-specific age-adjusted incidence, 5-year survival and mortality rates of bladder cancer (BCa) in the United States, between 1973 and 2009.Materials and methodsA total of 148,315 BCa patients were identified in the Surveillance, Epidemiology and End Results database, between years 1973 and 2009. Incidence, mortality, and 5-year cancer-specific survival rates were calculated. Temporal trends were quantified using the estimated annual percentage change (EAPC) and linear regression models. All analyses were stratified according to disease stage, and further examined according to sex, race, and age groups.ResultsIncidence rate of BCa increased from 21.0 to 25.5/100,000 person-years between 1973 and 2009. Stage-specific analyses revealed an increase incidence for localized stage: 15.4–20.2 (EAPC: +0.5%, p < 0.001) and distant stage: 0.5–0.8 (EAPC: +0.7%, p = 0.001). Stage-specific 5-year survival rates increased for all stages, except for distant disease. No significant changes in mortality were recorded among localized (EAPC: ?0.2%, p = 0.1) and regional stage (EAPC: ?0.1%, p = 0.5). An increase in mortality rates was observed among distant stage (EAPC: +1.0%, p = 0.005). Significant variations in incidence and mortality were recorded when estimates were stratified according to sex, race, and age groups.DiscussionAlbeit statistically significant, virtually all changes in incidence and mortality were minor, and hardly of any clinical importance. Little or no change in BCa cancer control outcomes has been achieved during the study period.     

MDM2 promoter polymorphism is associated with increased susceptibility to hepatocellular carcinoma in Turkish population

Background: The mouse double minute 2 (MDM2) gene represents one of the central nodes in the p53 pathway. A naturally occurring T/G single nucleotide polymorphism (SNP) in the intronic promoter of MDM2, SNP309 (rs2279744), was shown to influence MDM2 expression and p53 activity. SNP in the promoter region of MDM2 gene has recently been shown to be associated with accelerated tumor formation in both hereditary and sporadic cancers in humans. In this study, we aim to evaluate the association of SNP309 with the risk of hepatocellular carcinoma (HCC) development among Turkish population. Methods: MDM2 SNP309 polymorphism was investigated in 110 confirmed subjects with HCC and 110 cancer-free control subjects matched on age, gender, smoking and alcohol consumption by using a polymerase chain reaction-restriction fragment length polymorphism assay. Results: The allele frequencies of case subjects (T, 0.48; G, 0.52) were significantly different from those of control subjects (T, 0.65; G, 0.35) (p = 0.003). The proportion of GG genotype of the SNP309 in patients with HCC (26%) was significantly higher than that in patients without HCC (14%). We observed that compared with the TT genotype, the genotypes containing G allele [TG (OR, 2.19; 95% CI, 1.18–4.07; p = 0.013) or GG (OR, 3.63; 95% CI, 1.65–8.00; p = 0.001)] were associated with significant increased susceptibility to HCC. Conclusion: Our findings suggest that the MDM2 promoter SNP309 G allele is associated with presence of HCC in Turkish population.     

An in situ study of bioenergetic properties of human colorectal cancer: The regulation of mitochondrial respiration and distribution of flux control among the components of ATP synthasome

The aim of this study is to characterize the function of mitochondria and main energy fluxes in human colorectal cancer (HCC) cells. We have performed quantitative analysis of cellular respiration in post-operative tissue samples collected from 42 cancer patients. Permeabilized tumor tissue in combination with high resolution respirometry was used.Our results indicate that HCC is not a pure glycolytic tumor and the oxidative phosphorylation (OXPHOS) system may be the main provider of ATP in these tumor cells. The apparent Michaelis–Menten constant (K_m) for ADP and maximal respiratory rate (V_m) values were calculated for the characterization of the affinity of mitochondria for exogenous ADP: normal colon tissue displayed low affinity (K_m = 260 ± 55 μM) whereas the affinity of tumor mitochondria was significantly higher (K_m = 126 ± 17 μM). But concurrently the V_m value of the tumor samples was 60–80% higher than that in control tissue. The reason for this change is related to the increased number of mitochondria. Our data suggest that in both HCC and normal intestinal cells tubulin β-II isoform probably does not play a role in the regulation of permeability of the MOM for adenine nucleotides.The mitochondrial creatine kinase energy transfer system is not functional in HCC and our experiments showed that adenylate kinase reactions could play an important role in the maintenance of energy homeostasis in colorectal carcinomas instead of creatine kinase.Immunofluorescent studies showed that hexokinase 2 (HK-2) was associated with mitochondria in HCC cells, but during carcinogenesis the total activity of HK did not change. Furthermore, only minor alterations in the expression of HK-1 and HK-2 isoforms have been observed.Metabolic Control analysis showed that the distribution of the control over electron transport chain and ATP synthasome complexes seemed to be similar in both tumor and control tissues. High flux control coefficients point to the possibility that the mitochondrial respiratory chain is reorganized in some way or assembled into large supercomplexes in both tissues.     

Bayesian area–age–period–cohort model with carcinogenesis age effects in estimating cancer mortality

Objective: Area–age–period–cohort (AAPC) model has been widely used in studying the spatial and temporal pattern of disease incidence and mortality rates. However, lack of biological plausibility and ease of interpretability on temporal components especially for age effects are generally the weakness of AAPC models. We develop a Bayesian AAPC model where carcinogenesis age effect is incorporated to explain age effects from the underlying disease process. An autoregressive prior structure and an arbitrary linear constraint are used to solve the nonidentifiability issues. Methods: Two multistage carcinogenesis models are employed to derive the hazard functions to substitute the age effects in the AAPC models. The Iowa county-wide lung cancer mortality data are used for the model fitting and Deviance Information Criteria (DIC) is used for model comparison. Results: Our study shows that conventional AAPC model (DIC = 19,231.30), AAPC model with Armitage–Doll age effect (DIC = 19,233.00) and with two-stage clonal expansion (TSCE) age effect (DIC = 19,234.70) achieved the similar DIC values which indicated consistent model fitting among three models. The spatial pattern shows that the high spatial effects are clustered in the south of Iowa and also in largely populated areas. The lung cancer mortality rate is continuously declining by birth cohorts while increasing by the calendar period until 2000–2004. The age effects show an increasing pattern over time which can be easily explained by Armitage–Doll carcinogenesis model since we assume a log-linear relationship between age and hazard function. Conclusions: Our finding suggests that the proposed Bayesian AAPC model can be used to replace the conventional AAPC model without affecting model performance while providing a more biological sound approach from the underlining disease process.     

Provider recommendation for colorectal cancer screening: Examining the role of patients’ socioeconomic status and health insurance

Background: Provider recommendation for colorectal cancer (CRC) screening test has been shown as a strong predictor of patients’ decision to be screened. Evidence of factors associated with provider recommendation remains limited and inconsistent. The present study sought to examine the association between provider recommendation for colorectal cancer screening and patients’ socioeconomic status (SES) and insurance status using national survey data for 2005. Methods: Analyses were based on 2948 adult aged 50 and older who participated in the 2005 Health Information National Trend Survey (HINTS). Multivariate logistic regression models were used to determine whether the indicators of SES (income and educational level) and insurance status have any impact on provider recommendation. Results: Our study found a strong association between recall of health care provider recommendation and reported recent screening testing after controlling for other patient characteristics. When all the study population were included in the analysis, those who had lower than high school education and high school graduates were less likely to have received provider recommendation than those with higher than high school education (OR = 0.49; 95%CI = 0.32–0.73 and OR = 0.60; 95%CI = 0.47–0.78 respectively). Income and insurance were not significant predictors. Education remained significantly associated with provider recommendation when only those who had made one or more medical visits in the past year were included in the analyses. Conclusions: Patient's educational level – but not income or insurance status – was related to provider recommendation for CRC screening. To increase awareness of colorectal cancer risks and the benefit of screening, health care providers need to make a concerted effort to recommend colorectal cancer screening to all relevant patients, regardless of socioeconomic status and other personal characteristics.     

Cyclin D1 G870A polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: Case–control study

Background: A common G to A polymorphism (G870A) in the splice donor region of exon 4 of cyclin D1 (CCND1) gene generates two mRNAs (cyclin D1a and D1b) through an alternative splicing at the site of this polymorphism. Cyclin D1a and b proteins differ in their COOH-terminus, a region involved in protein degradation. We examined the association between this CCDN1 genotype and the susceptibility to hepatocellular carcinoma (HCC) in a Turkish population. Methods: The genotype frequency of this polymorphism was determined by using a polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. Hospital-based case–control study was designed consisting of 160 diagnosis subjects with hepatocellular carcinoma and 160 cancer-free control subjects matched on age, gender, smoking and alcohol status. Results: The allele frequencies of case subjects (A, 0.55; G, 0.45) were significantly different from those of control subjects (A, 0.42; G, 0.58) (p = 0.002). The odds ratios (ORs) for the CCND1 870 GA and AA genotypes when compared with the GG genotypes were 1.39 (95% confidence interval [CI] 0.82–2.36, p = 0.22) and 2.52 (95% CI 1.38–4.62, p = 0.003) respectively. The presence of at least one CCND1 870A allele was associated with increased risk for HCC (OR, 1.73; 95% CI, 1.06–2.82, p = 0.03). When combining the GG and GA genotypes as a reference genotype, we found that the OR for the AA genotype was 2.06 (95% CI 1.24–3.44, p = 0.006). Conclusion: Our results suggest that the CCND1 G870A single nucleotide polymorphism is associated with an increased risk of HCC in our Turkish population.