scholarly journals Diabetes and Insulin Therapy, but Not Metformin, Are Related to Hepatocellular Cancer Risk

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Luca Miele ◽  
Cristina Bosetti ◽  
Federica Turati ◽  
Gianlodovico Rapaccini ◽  
Antonio Gasbarrini ◽  
...  
Keyword(s):  
Hepatocellular Cancer ◽  
Excess Risk ◽  
Diabetes Diagnosis ◽  
Logistic Regression Models ◽  
Metabolic Conditions ◽  
Never Smokers ◽  
Fold Excess ◽  
Control Study

Introduction. Metabolic conditions, including type 2 diabetes, have been related to hepatocellular carcinoma (HCC) risk. We have further analyzed the role of diabetes and antidiabetic treatments on HCC.Methods. Data derived from a hospital-based case-control study (Italy, 2005–2012) on 224 HCC patients and 389 controls. Odds ratios (ORs) were estimated using multiple logistic regression models.Results. Sixty-nine (30.9%) cases versus 52 (13.5%) controls reported a diabetes diagnosis, corresponding to a multivariate OR of 2.25 (95% confidence interval, CI = 1.42–3.56). A stronger excess risk emerged for a longer time since diabetes diagnosis (OR = 2.96 for <10 years and 5.33 for ≥10 years). Oral therapies were inversely, though not significantly, related to HCC risk, OR being 0.44 for metformin and 0.88 for sulfonylureas; conversely, insulin was nonsignificantly directly associated (OR = 1.90). Compared to nondiabetic subjects who were never smokers, those who were diabetics and ever smokers had an OR of 6.61 (95% CI 3.31–13.25).Conclusion. Our study confirms an over 2-fold excess HCC risk in diabetics, with a stronger excess risk in diabetic subjects who are also tobacco smokers. Metformin may decrease the risk of HCC, whereas insulin may increase the risk.

scholarly journals Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Julia K. Goodrich ◽  
Moriel Singer-Berk ◽  
Rachel Son ◽  
Abigail Sveden ◽  
Jordan Wood ◽  
...  
Keyword(s):  
Case Control Study ◽  
Rare Variants ◽  
Standard Of Care ◽  
Polygenic Scores ◽  
Monogenic Diseases ◽  
Metabolic Conditions ◽  
The Uk ◽  
Control Study ◽  
Polygenic Variation

AbstractHundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias.

scholarly journals TP53 rs1042522 C>G polymorphism and Wilms tumor susceptibility in Chinese children: a four-center case–control study

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Peng Liu ◽  
Zhenjian Zhuo ◽  
Wenya Li ◽  
Jiwen Cheng ◽  
Haixia Zhou ◽  
...  
Keyword(s):  
Significant Relationship ◽  
Wilms Tumor ◽  
Tp53 Gene ◽  
Chinese Children ◽  
Logistic Regression Models ◽  
Tumor Susceptibility ◽  
Tumor Risk ◽  
Larger Sample ◽  
Control Study

Abstract Wilms tumor is the most common renal malignancy that occurs in children. TP53 gene is considered as a tumor-suppressing gene through controlling cell growth. TP53 gene rs1042522 C>G (Arg72Pro) polymorphism is widely investigated in various types of cancers. However, it is not established if TP53 rs1042522 C>G polymorphism is a candidate variant for Wilms tumor risk. The aim of the study was to determine whether TP53 rs1042522 C>G polymorphism is responsible for the risk of Wilms tumor in Chinese children. All subjects (355 cases and 1070 controls) from four centers of China were genotyped for rs1042522 C>G polymorphism. The effect of rs1042522 C>G polymorphism on Wilms tumor prevalence was analyzed using logistic regression models. We failed to detect a significant relationship between rs1042522 C>G polymorphism and Wilms tumor risk. Further stratification analysis also could not detect a significant relationship. We conclude that TP53 rs1042522 C>G polymorphism might not have enough impact on the risk of Wilms tumor. More validation study with larger sample size will be required to better define the role of TP53 rs1042522 C>G polymorphism in Wilms tumor risk.

PADI4 polymorphism predisposes male smokers to rheumatoid arthritis

2010 ◽  
Vol 70 (3) ◽  
pp. 512-515 ◽  
Author(s):  
Yuta Kochi ◽  
Mohamed M Thabet ◽  
Akari Suzuki ◽  
Yukinori Okada ◽  
Nina A Daha ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Smoking Status ◽  
Arginine Deiminase ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Logistic Regression Models ◽  
Environmental Interactions ◽  
Never Smokers ◽  
European Populations

ObjectiveTo elucidate the differential role of peptidyl arginine deiminase 4 (PADI4) polymorphism in rheumatoid arthritis (RA) between Asian and European populations, possible gene–environmental interactions among the PADI4 polymorphism, sex and smoking status were analysed.MethodsThree independent sets of case–control samples were genotyped for single-nucleotide polymorphisms in PADI4; Japanese samples (first set, 1019 RA patients, 907 controls; second set, 999 RA patients, 1128 controls) using TaqMan assays and Dutch samples (635 RA patients, 391 controls) using Sequenom MassARRAY platform. The association of PADI4 with RA susceptibility was evaluated by smoking status and sex in contingency tables and logistic regression models.ResultsIn the first set of Japanese samples, PADI4 polymorphism (rs1748033) showed a greater risk in men (ORallele 1.39; 95% CI 1.10 to 1.76; ptrend=0.0054) than in women and in ever-smokers (ORallele 1.25; 95% CI 1.02 to 1.53; ptrend=0.032) than in never-smokers. Moreover, the highest risk was seen in male ever-smokers (ORallele 1.46; 95% CI 1.12 to 1.90; ptrend=0.0047). Similar trends were observed in the second set of Japanese samples as well as in Dutch samples.ConclusionPADI4 polymorphism highly predisposes male smokers to RA, and the genetic heterogeneity observed between Asian and European populations may be partly explained by differences in smoking prevalence among men.

Inflammatory potential of diet and risk for hepatocellular cancer in a case–control study from Italy

2015 ◽  
Vol 115 (2) ◽  
pp. 324-331 ◽  
Author(s):  
Nitin Shivappa ◽  
James R. Hébert ◽  
Jerry Polesel ◽  
Antonella Zucchetto ◽  
Anna Crispo ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Case Control Study ◽  
Hepatocellular Cancer ◽  
Serum Markers ◽  
Case Control ◽  
Logistic Regression Models ◽  
Inflammatory Index ◽  
Increased Risk ◽  
History Of ◽  
Control Study

AbstractInflammation and diet have been suggested to be important risk factors for hepatocellular cancer (HCC). This Italian multicentre hospital-based case–control study conducted between 1999 and 2002 and including 185 cases with incident, histologically confirmed HCC, and 404 controls hospitalised for acute non-neoplastic diseases provided an opportunity to investigate the association between HCC and the dietary inflammatory index (DII). The DII was computed on the basis of dietary intake assessed 2 years before the date of interview by a validated sixty-three-item FFQ. Logistic regression models were used to estimate OR adjusted for age, sex, study centre, education, BMI, smoking, physical activity, serum markers of hepatitis B and C infection and energy intake. Energy adjustment for DII was performed using the residual method. Participants in the highest tertile of DII scores (i.e. with a more pro-inflammatory diet) had a higher risk for HCC (ORtertile 3 v, 1 2·43; 95 % CI 1·27, 4·68; Ptrend=0·03). When stratified by the presence or absence of hepatitis B/C infection and sex, DII was strongly associated with HCC in hepatitis B- and C-negative participants (ORtertile 3 v. 1 4·18; 95 % CI 1·53, 11·39; Ptrend=0·02) and among males (ORtertile 3 v. 1 3·60; 95 % CI 1·65, 7·87; Ptrend=0·001). These results indicate that a pro-inflammatory diet is associated with increased risk for HCC, in those without a history of hepatitis B/C infection and among males.

scholarly journals The Association of Mitochondrial Content with Prevalent and Incident Type 2 Diabetes

2010 ◽  
Vol 95 (4) ◽  
pp. 1909-1915 ◽  
Author(s):  
Erwin Reiling ◽  
Charlotte Ling ◽  
André G. Uitterlinden ◽  
Esther van't Riet ◽  
Laura M. C. Welschen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
The Netherlands ◽  
Small Samples ◽  
Incident Type ◽  
Incident Type 2 Diabetes ◽  
Twin Families ◽  
Male Specific ◽  
Control Study

Abstract Context: It has been shown that mitochondrial DNA (mtDNA) content is associated with type 2 diabetes (T2D) and related traits. However, empirical data, often based on small samples, did not confirm this observation in all studies. Therefore, the role of mtDNA content in T2D remains elusive. Objective: In this study, we assessed the heritability of mtDNA content in buccal cells and analyzed the association of mtDNA content in blood with prevalent and incident T2D. Design and Setting: mtDNA content from cells from buccal and blood samples was assessed using a real-time PCR-based assay. Heritability of mtDNA content was estimated in 391 twins from the Netherlands Twin Register. The association with prevalent T2D was tested in a case control study from The Netherlands (n = 329). Incident T2D was analyzed using prospective samples from Finland (n = 444) and The Netherlands (n = 238). Main Outcome Measures: We measured the heritability of mtDNA content and the association of mtDNA content in blood with prevalent and incident T2D. Results: A heritability of mtDNA content of 35% (19–48%) was estimated in the twin families. We did not observe evidence of an association between mtDNA content and prevalent or incident T2D and related traits. Furthermore, we observed a decline in mtDNA content with increasing age that was male specific (P = 0.001). Conclusion: In this study, we show that mtDNA content has a heritability of 35% in Dutch twins. There is no association between mtDNA content in blood and prevalent or incident T2D and related traits in our study samples.

scholarly journals Mediterranean Diet and Bladder Cancer Risk in Italy

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1061 ◽  
Author(s):  
Francesca Bravi ◽  
Maria-Eleni Spei ◽  
Jerry Polesel ◽  
Matteo Di Maso ◽  
Maurizio Montella ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Mediterranean Diet ◽  
Epidemiological Data ◽  
Italian Population ◽  
Logistic Regression Models ◽  
The Mediterranean ◽  
Never Smokers ◽  
Bladder Carcinomas ◽  
Diet Score ◽  
Control Study

Previous studies have reported that Mediterranean diet is inversely related to the risk of several neoplasms; however, limited epidemiological data are available for bladder cancer. Thus, we examined the association between Mediterranean diet and this neoplasm in an Italian multicentric case-control study consisting of 690 bladder cancer cases and 665 controls. We assessed the adherence to the Mediterranean diet via a Mediterranean Diet Score (MDS), which represents the major characteristics of the Mediterranean diet and ranges from 0 to 9 (from minimal to maximal adherence, respectively). We derived odds ratios (ORs) of bladder cancer according to the MDS score from multiple logistic regression models, allowing for major confounding factors. The ORs of bladder cancer were 0.72 (95% confidence interval, CI, 0.54–0.98) for MDS of 4–5 and 0.66 (95% CI, 0.47–0.93) for MDS of 6–9 (p for trend = 0.02) compared to MDS = 0–3. Results were similar in strata of sex, age, and education, while the risk appeared somewhat lower in never-smokers and patients with pT1–pT4 bladder carcinomas. Among individual components of the MDS, we observed inverse associations for greater consumption of legumes, vegetables, and fish. In our study, which was carried out on an Italian population, the higher adherence to the Mediterranean diet was related to a lower risk of bladder cancer.

scholarly journals Comorbidity status of deceased COVID-19 in-patients in Italy

2021 ◽  
Author(s):  
Davide Liborio Vetrano ◽  
Clare Tazzeo ◽  
Luigi Palmieri ◽  
Alessandra Marengoni ◽  
Alberto Zucchelli ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Older Persons ◽  
Logistic Regression Models ◽  
Neuropsychiatric Diseases ◽  
Clinical Profiles ◽  
Comorbidity Status ◽  
Diabetes And Obesity

Abstract Background Most COVID-19-related deaths have occurred in older persons with comorbidities. Specific patterns of comorbidities related to COVID-19 deaths have not been investigated. Methods A random sample of 6085 individuals in Italy who died in-hospital with confirmed COVID-19 between February and December 2020 were included. Observed to expected (O/E) ratios of disease pairs were computed and logistic regression models were used to determine the association between disease pairs with O/E values ≥ 1.5. Results Six pairs of diseases exhibited O/E values ≥ 1.5 and statistically significant higher odds of co-occurrence in the crude and adjusted analyses: (1) ischemic heart disease and atrial fibrillation, (2) atrial fibrillation and heart failure, (3) atrial fibrillation and stroke, (4) heart failure and COPD, (5) stroke and dementia, and (6) type 2 diabetes and obesity. Conclusion In those deceased in-hospital due to COVID-19 in Italy, disease combinations defined by multiple cardio-respiratory, metabolic, and neuropsychiatric diseases occur more frequently than expected. This finding indicates a need to investigate the possible role of these clinical profiles in the chain of events that lead to death in individuals who have contracted SARS-CoV-2.

scholarly journals Renalase gene Glu37Asp polymorphism affects susceptibility to diabetic retinopathy in type 2 diabetes mellitus

2021 ◽  
Author(s):  
Monika Buraczynska ◽  
Karolina Gwiazda-Tyndel ◽  
Bartłomiej Drop ◽  
Wojciech Zaluska
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Case Control Study ◽  
Microvascular Complications ◽  
Monoamine Oxidase Activity ◽  
Allele Distribution ◽  
Insight Into ◽  
Control Study

Abstract Aims Renalase (RNLS) is an enzyme with monoamine oxidase activity that metabolizes circulating catecholamines. The RNLS gene Asp37Glu missense polymorphism (rs2296545) has been associated with hypertension, cardiac hypertrophy and dysfunction, and stroke. The purpose of our study was to investigate the potential involvement of this polymorphism in the microvascular complications of type 2 diabetes (T2DM). Methods In this case–control study, the polymorphism was genotyped in 860 patients with T2DM and 400 healthy controls. The genotype and allele distribution was compared in subgroups of patients: with diabetic nephropathy (DN+) (n = 405) versus DN− (independently of the presence of DR) and, similarly, patients with diabetic retinopathy (DR+) (n = 328) versus DR− (independently of the presence of DN). Results No significant association was detected between analyzed polymorphism and DN. In contrast, the retinopathy subgroup showed a significantly higher frequency of G allele (OR 1.4, 95% CI 1.16–1.72, p = 0.0005) and GG genotype (OR 1.86, 95% CI 1.26–2.75, p = 0.001) than DR− patients. The effect of RNLS Glu37Asp polymorphism on DR remained significant after adjustments for age, gender, BMI, and duration of T2DM (p = 0.005). Conclusions This is the first study to investigate RNLS gene polymorphism in microvascular complications of T2DM. The results suggest that RNLS rs2296545 SNP might be considered a risk factor for diabetic retinopathy in T2DM patients. This can provide new insight into the role of renalase gene in the pathophysiology of microvascular complications of diabetes.

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