Statin use and risk of liver cancer: Evidence from two population-based studies

Epidemiological studies of statin use and liver cancer risk have produced conflicting results. We examined the association between statin use and risk of primary liver cancer in two large independent study populations taking account of important covariates and main indications of statins such as high cholesterol and chronic liver disease. We performed a nested case–control study within the Scottish Primary Care Clinical Informatics Unit (PCCIU) database. Five controls were matched to cases with primary liver cancer and we used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with statin use. We also conducted a prospective cohort study within the UK Biobank using self-reported statin use and cancer-registry recorded primary liver cancer outcomes. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. In the PCCIU case–control analysis, 434 liver cancer cases were matched to 2,103 controls. In the UK Biobank cohort, 182 out of 475,768 participants developed incident liver cancer. Statin use was associated with 39% lower risk of liver cancer in the PCCIU (adjusted OR 0.61, 95% CI 0.43–0.87). When we examined specific subtypes of liver cancer in the UK Biobank, statin use was associated with lower risk of hepatocellular carcinoma (HCC; adjusted HR, 0.48; 95% CI, 0.24–0.94) but not intrahepatic bile duct carcinoma (IBDC; adjusted HR, 1.09; 95% CI, 0.45–2.64). In conclusion, we found a consistent inverse relationship between statin use and risk of primary liver cancer which was only seen for HCC but not IBDC.     

Statins and the risk of pancreatic cancer in Type 2 diabetic patients—A population‐based cohort study

The aim of this study was to determine whether statin use exerts a protective effect against pancreatic cancer in Type 2 diabetic patients. A retrospective population‐based cohort study was designed to analyze the National Health Insurance Research database (NHIRD) from 1997–2010 in Taiwan. A total of 1,140,617 patients with a first‐time diagnosis of Type 2 diabetes were enrolled. The event was defined as newly diagnosed pancreatic cancer. A Cox proportional hazards regression model with time‐dependent covariates was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of pancreatic cancer associated with statin use in the diabetic cohort. A total of 2,341 patients with newly diagnosed pancreatic cancer were identified in the diabetic cohort during the follow‐up period of 6,968,217.1 person‐years. In this cohort, 450,282 patients were defined as statin users (statin use ≥28 cumulative defined daily dose [cDDD] in 1 year) and 0.14% had pancreatic cancer; 690,335 patients were statin nonusers (statin use <28 cDDD in 1 year) and 0.25% had pancreatic cancer. Statin use significantly decreased the risk of pancreatic cancer (adjusted HRs: 0.78 in 28–83 cDDD per year; 0.48 in 84–180 cDDD per year; and 0.33 in >180 cDDD per year) after adjusting for multiple confounders. There was a significant dose‐effect of statin use for the risk of pancreatic cancer (p for trend: <0.001). Statin use may be associated with a reduced risk of pancreatic cancer in Type 2 diabetic patients. More research is needed to clarify this association.     

The occurrence of hepatocellular carcinoma in different risk stratifications of clinically noncirrhotic nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) may be a cause of hepatocellular carcinoma (HCC), but its high prevalence challenges current surveillance strategies. We aimed to evaluate HCC incidences in different risk stratifications for noncirrhotic NAFLD. Using Taiwan's National Health Insurance Research Database, we located 31,571 patients with NAFLD between the years 1998 and 2012. After excluding other causes of hepatitis, underlying cirrhosis or malignancy, 18,080 patients were recruited for final analysis. Cumulative incidences of HCC were analyzed after adjusting for competing mortality. With a median follow‐up duration of 6.32 years in the study cohort, the 10‐year cumulative incidence of HCC was 2.73% [95% confidence interval (CI): 1.69–3.76%]. Hepatoprotectant was used as a surrogate marker for elevated serum alanine transaminase (ALT). After adjusting for age, gender, hypertension, hypercholesterolemia, diabetes mellitus, gout, statin use, metformin use and aspirin use, elevated ALT was independently associated with an increased HCC risk [hazard ratio (HR) 6.80, 95% CI: 3.00–15.42; p < 0.001]. Multivariate stratified analysis verified this association in all subgroups (HR> 1.0). Moreover, increased age (HR 1.08 per year, 95% CI: 1.05–1.11) and statin use (HR 0.29, 95% CI: 0.12–0.68) were also identified as independent risk factors. The 10‐year cumulative HCC incidence was highest in older (age >55 years) patients with ALT elevation (12.41%, 95% CI: 5.99–18.83%), but lowest in younger patients without ALT elevation (0.36%, 95% CI: 0–1.08%). The incidence of HCC was relatively low in patients with clinically noncirrhotic NAFLD, however, HCC risk was significantly increased in older patients experiencing an elevated serum ALT.     

Type 2 diabetes mellitus,insulin‐use and risk of bladder cancer in a large cohort study

Type 2 diabetes mellitus (T2DM) is associated with increased bladder cancer incidence in some, but not all, studies. Many studies had limited statistical power and few examined risk by insulin‐use, duration of diabetes or cancer stage. We examined the association between T2DM and bladder cancer incidence in the Cancer Prevention Study II Nutrition Cohort, a large prospective study with information on insulin‐use and duration of diabetes. Diabetes and insulin‐use were ascertained from a questionnaire at study enrollment in 1992 or 1993 and updated in 1997 and every 2 years thereafter. During follow‐up through 2007, 1,852 cases of incident bladder cancer were identified among 172,791 participants. Multivariable adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using extended Cox regression modeling. There were no associations of T2DM with the risk of bladder cancer overall (RR = 1.01, 95% CI: 0.87–1.17), noninvasive disease (RR = 0.93, 95% CI: 0.76–1.14) or invasive disease (RR = 1.13, 95% CI: 0.91–1.40). Compared to participants without T2DM, risk of invasive bladder cancer was higher among participants who had had T2DM for >15 years (RR = 1.63, 95% CI: 1.09–2.43) and among those using insulin (RR = 1.64, 95% CI: 1.18–2.27). These results do not support an association of T2DM with overall bladder cancer incidence, but do suggest positive associations of long‐term T2DM and insulin‐use or other factors correlated with severe diabetes, with invasive bladder cancer incidence.     

Prospective evaluation of type 2 diabetes mellitus on the risk of primary liver cancer in Chinese men and women

BackgroundNo prospective study has investigated the relationship between type 2 diabetes mellitus (T2DM) and the risk of primary liver cancer (PLC) in mainland China, and little is known about the effect of diabetes duration on PLC risk.DesignData from two population-based cohorts (the Shanghai Men's Health Study, SMHS, 2002–2006 and the Shanghai Women's Health Study, SWHS, 1996–2000) were thus used to assess the associations among T2DM, diabetes duration and PLC risk in Chinese population.ResultsDuring follow-up through 2009, 344 incident PLC cases were identified among 60 183 men and 73 105 women. T2DM is significantly associated with the increased risk of PLC in both men [hazard ratio (HR) = 1.63, 95% confidence interval (CI) 1.06–2.51] and women (HR = 1.64, 95% CI 1.03–2.61). The highest risk of incident liver cancer was observed in the first 5 years after diabetes diagnosis, and decreased substantially with the prolonged diabetes duration (P_trend < 0.001). No synergistic interaction in the development of PLC was found between diabetes and other known risk factors.ConclusionsT2DM is associated with the increased risk of subsequent liver cancer within 5 years after diagnosis in Chinese population, suggesting that hyperinsulinaemia rather than hyperglycaemia is more likely to be a primary mediator for this association.     

Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma

BACKGROUND:

Despite the observed association between diabetes mellitus and hepatocellular carcinoma (HCC), little is known about the effect of diabetes duration before HCC diagnosis and whether some diabetes medications reduced the risk of HCC development. This objective of the current study was to determine the association between HCC risk and diabetes duration and type of diabetes treatment.

METHODS:

A total of 420 patients with HCC and 1104 healthy controls were enrolled in an ongoing hospital‐based case‐control study. Multivariate logistic regression models were used to adjust for HCC risk factors.

RESULTS:

The prevalence of diabetes mellitus was 33.3% in patients with HCC and 10.4% in the control group, yielding an adjusted odds ratio (AOR) of 4.2 (95% confidence interval [95% CI], 3.0‐5.9). In 87% of cases, diabetes was present before the diagnosis of HCC, yielding an AOR of 4.4 (95% CI, 3.0‐6.3). Compared with patients with a diabetes duration of 2 to 5 years, the estimated AORs for those with a diabetes duration of 6 to 10 years and those with a diabetes duration >10 years were 1.8 (95% CI, 0.8‐4.1) and 2.2 (95% CI, 1.2‐4.8), respectively. With respect to diabetes treatment, the AORs were 0.3 (95% CI, 0.2‐0.6), 0.3 (95% CI, 0.1‐0.7), 7.1 (95% CI, 2.9‐16.9), 1.9 (95% CI, 0.8‐4.6), and 7.8 (95% CI, 1.5‐40.0) for those treated with biguanides, thiazolidinediones, sulfonylureas, insulin, and dietary control, respectively.

CONCLUSIONS:

Diabetes appears to increase the risk of HCC, and such risk is correlated with a long duration of diabetes. Relying on dietary control and treatment with sulfonylureas or insulin were found to confer the highest magnitude of HCC risk, whereas treatment with biguanides or thiazolidinediones was associated with a 70% HCC risk reduction among diabetics. Cancer 2010. © 2010 American Cancer Society.     

Statin use and prostate cancer risk in a large population-based setting

BACKGROUND: Statins are a commonly used cholesterol-lowering drug, which also have the potential to affect cancer risk and progression. Results from previous studies offer mixed conclusions. METHODS: To evaluate the relation between statin use and prostate cancer risk, we conducted a retrospective cohort study during 1 January 1990 to 31 August 2005 among men 45-79 years receiving care within Group Health, an integrated healthcare delivery system. Information on statin use and covariates were obtained from health plan databases. We identified incident prostate cancer cases through the Surveillance, Epidemiology, and End Results cancer registry. We used Cox proportional hazards models to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for prostate cancer among statin users compared to non-users. RESULTS: Among 83,372 men studied, median follow-up time was 5.7 years and 2,532 prostate cancer cases were identified. About 14.4% used statins over the study period and median duration of use was 3.3 years. Compared to non-users, hydrophobic statin users had a reduced risk of prostate cancer (HR = 0.79; 95% CI, 0.66-0.94), and results are suggestive of a reduced risk among ever users of statins (HR = 0.88; 95% CI, 0.76-1.02) and hydrophilic statin users (HR = 0.67; 95% CI, 0.33-1.34). There was no trend in risk by duration of statin use, and no association between statin use and cancer aggressiveness, stage, or grade. CONCLUSION: Overall, this study does not support an associated between statin use and prostate cancer but a reduced risk cannot be ruled out.     

Risk of Cause‐Specific Death in Individuals with Cancer—Modifying Role Diabetes,Statins and Metformin

Both diabetes mellitus (DM) and cancer are common diseases and they frequently occur in the same patients. We investigated the all‐cause and cause‐specific mortality dynamics in relation to baseline DM, statin use and metformin use. The study population consisted of 39,900 incident cancer cases from Finland, 19,822 patients were free of DM at the start of follow‐up and 20,078 had DM. Mortality from all causes, and cancer, cardiovascular (CVD) and other causes was analysed using Poisson regression model with the following variables: sex, age, DM, statin and metformin usage in baseline, cancer type and stage and calendar period. Statin usage was associated with a reduced cancer‐specific mortality with incidence rate ratio (IRR) 0.72 (95% confidence interval 0.69–0.74), IRR for CVD mortality was 0.95 (0.88–1.02) and for other causes 0.64 (0.56–0.74). In a sub‐population of DM patients, IRR for metformin in all‐cause mortality was 0.74 (0.71–0.78), in cancer mortality 0.75 (0.72–0.79), in CVD mortality 0.75 (0.68–0.83) and other causes 0.68 (0.60–0.78). In conclusion, our register‐based study of survival after cancer diagnosis showed that patients with diabetes had substantially poorer outcome in all measures. An association between baseline statin usage and lower all‐cause, cancer and cardiovascular mortality was modified by cancer type. The effect of statin use was largest for breast and colorectal cancer. Metformin usage in a subpopulation of oral antidiabetic users was in general associated with lower mortality, but this association was modified by cancer type. The association was strongest for liver, colorectal and breast cancer.     

Metformin use among type 2 diabetics and risk of pancreatic cancer in a clinic‐based case–control study

A better understanding of the association between diabetes and pancreatic cancer (PC) may inform prevention and/or early detection strategies. Metformin has been associated with reduced risk of certain cancers, including PC, in some observational clinical studies. We assessed whether metformin use was associated with PC risk among those with type 2 diabetes (DM2), and whether metformin use modulated the association between DM2 and risk of PC. In total, 536 PC cases and 869 frequency‐matched controls were recruited predominantly from University of California San Francisco medical clinics from 2006 to 2011. Eligible participants completed direct interviews using a structured risk factor questionnaire. The association between metformin use and PC risk was assessed using propensity score‐weighted unconditional logistic regression methods in analyses restricted to diabetics and adjusted multivariable logistic models in the total study population. Ever use of metformin was not associated with PC risk in analyses restricted to DM2 (N = 170) participants (adjusted OR: 1.01, 95% CI: 0.61–1.68). In the total study population (N = 1,405) using nondiabetics as the referent group, PC risk was inversely associated with diabetes duration (p_trend < 0.001). Further, when DM2 participants were grouped by ever/never use of metformin and compared with nondiabetics, metformin use did not affect the association between DM2 and PC risk (never users: OR: 1.44, 95% CI: 0.78–2.67; ever users: OR: 1.19, 95% CI: 0.72–1.99). Results from our clinic‐based case–control study suggest that metformin use is not associated with PC risk among those with DM2 and does not alter the association between DM2 and PC risk.     

Effect of different types of smoking and synergism with hepatitis C virus on risk of hepatocellular carcinoma in American men and women: case-control study

The International Agency for Research on Cancer has declared smoking to be a risk factor for hepatocellular carcinoma (HCC). However, passive exposure to cigarette smoke and use of noncigarette tobacco products on the risk of HCC has not been examined. Therefore, we evaluated the independent effects of different types of smoking exposure along with multiple risk factors for HCC and determined whether the magnitude of smoking was modified by other risk factors in men and women. We conducted a case-control study at The University of Texas M. D. Anderson Cancer Center where 319 HCC patients and 1,061 healthy control subjects were personally interviewed for several HCC risk factors. Multivariate logistic regression analysis was performed to estimate the adjusted odds ratio (AOR) and 95% confidence interval (CI) for each potential risk factor. Use of smokeless tobacco (chewing tobacco and snuff), cigars, pipes and passive smoking exposure were not related to HCC among noncigarette smokers. However, regular cigarette smoking was associated with HCC in men: AOR, 1.9 (95% CI, 1.1-3.1). Heavy alcohol consumption was associated with HCC in women: AOR, 7.7 (95% CI, 2.3-25.1). Cigarette smoking interacted synergistically with chronic infection of hepatitis C virus in men: AOR, 136.3 (95% CI, 43.2-429.6) and with heavy alcohol consumption in women: AOR, 13.7 (95% CI, 3.2-57.9). We conclude that sex differences were observed in HCC relationship with cigarette smoking and alcohol consumption. Controlling for smoking exposure might be a prudent approach to the prevention of HCC, especially in patients with chronic viral hepatitis infections.     

Statin use and female reproductive organ cancer risk in a large population-based setting

Objective  Statins are an effective and commonly used cholesterol-lowering medication class, but their hypothesized effects on cancer risk remain uncertain. We evaluated the association between statin use and endometrial as well as ovarian cancer risks. Methods  We conducted a retrospective study with two cohorts of women aged 45–89 years during 1990–2004 within an integrated healthcare delivery system. Information on statin use and covariates were obtained from automated databases. We identified cancer cases through the Surveillance, Epidemiology, and End Results registry. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for incident invasive endometrial and ovarian cancers among statin users compared to nonusers. Results  Women were followed for a median of about six years. Among 73,336 women studied, 568 endometrial cancer cases were identified. During the study period, 6% of women used statins for at least one year and the median duration of use was 3.1 years. Although not statistically significant, we found a reduction in endometrial cancer risk among statin users (HR = 0.67; 95% CI: 0.39–1.17) compared to nonusers. We identified 326 ovarian cancer cases in a cohort of 93,619 women. There was also a nonsignificant decrease in ovarian cancer risk among statin users (HR = 0.69; 95% CI: 0.32–1.49). Conclusion  Our study does not support an association between statin use and endometrial as well as ovarian cancers, but a reduced risk cannot be ruled out.     

Associations between statin use and non‐Hodgkin lymphoma (NHL) risk and survival: a meta‐analysis

Evidence on the effect of statin use on non‐Hodgkin lymphoma (NHL) is not clear. We conducted a systematic review and meta‐analysis to examine the associations between statin use and NHL risk and survival. We searched multiple literature sources up to October 2014 and identified 10 studies on the risk of diagnosis with NHL and 9 studies on survival. Random effects model was used to calculate pooled odds ratio (PORs) for risk and pooled hazard ratio (PHR) for survival. Heterogeneity among studies was examined using the Tau‐squared and the I‐squared (I²) tests. Statin use was associated with reduced risk for total NHL (POR = 0.82, 95% CI 0.69–0.99). Among statin users, there was a lower incidence risk for marginal zone lymphoma (POR = 0.54, 95% CI 0.31–0.94), but this was not observed for other types of NHL. However, statin use did not affect overall survival (PHR = 1.02, 95% CI 0.99–1.06) or event‐free survival (PHR = 0.99, 95% CI 0.87–1.12) in diffuse large B‐cell lymphoma. There is suggestive epidemiological evidence that statins decrease the risk of NHL, but they do not influence survival in NHL patients. Copyright © 2015 John Wiley & Sons, Ltd.     

The relationship between new-onset diabetes mellitus and pancreatic cancer risk: A case-control study

Diabetes mellitus (DM) is widely considered to be associated with pancreatic cancer, however, whether DM is a cause or consequence of pancreatic cancer is controversial. In the present study, 1458 patients with pancreatic ductal adenocarcinoma (PDAC) and 1528 age-, sex- and sociodemographic variables-matched controls were recruited in two university-affiliated hospitals from 1st January 2000 to 31st December 2009. DM was defined as fasting blood glucose (FBG) level of 7.0 mmol/L or greater. An unconditional multivariable logistic regression analysis was used to estimate adjusted odds ratios (AORs) and 95% confidence interval (CI). Compared with controls, a moderate increased risk of PDAC was observed among cases with long-standing diabetes (?2-year duration), with an AOR (95% CI) of 2.11 (1.51-2.94). Interestingly, a significant higher risk was observed among cases with new-onset DM (<2-year duration), with an AOR of 4.43 (3.44-5.72) compared to controls without DM. In addition, we found a synergistic interaction between cigarette smoking and DM on modifying the risk of pancreatic cancer development (AOR = 6.17, 95% CI 3.82-9.94). Similarly, a synergistic interaction between new-onset DM and family history of pancreatic cancer was found for pancreatic cancer risk, with an AOR (95% CI) of 11.04 (2.51-48.53). This study suggested that DM could be both an early manifestation of pancreatic cancer and an aetiologic factor. Possible effect modification on DM by family history of pancreatic cancer and smoking status should be further explored in future aetiologic studies.     

Statin use and breast cancer risk in a large population-based setting.

BACKGROUND: Mechanistic studies suggest that 3-hydroxy-3-methylglutaryl CoA inhibitors (statins) reduce the risk of breast cancer. Observational studies offer mixed results. METHODS: To evaluate the relation between statin use and breast cancer risk, we conducted a cohort study among women ages 45 to 89 years within an integrated health care delivery system. Information on statin use and covariates were obtained from automated databases. We identified breast cancer cases through the Surveillance, Epidemiology, and End Results registry. We used Cox proportional hazards models to estimate the hazard ratios (HR) and 95% confidence intervals (95% CI) for invasive breast cancer among statin users compared with nonusers. RESULTS: Among 92,788 women studied from 1990 to 2004, median follow-up time was 6.4 years, and 2,707 breast cancer cases were identified. During the study period, 7.4% of women used statins for at least 1 year, and the median duration of use was 3.1 years. We found no difference in breast cancer risk among statin users (HR, 1.07; 95% CI, 0.88-1.29) compared with nonusers. Risk of breast cancer did not differ by duration of use (1-2.9, 3-4.9, or >or=5 years) or hydrophobic statin use. We found a suggestive increased risk of breast cancer among statin users of >or=5 years (HR, 1.27; 95% CI, 0.89-1.81 for any statins and HR, 1.47; 95% CI, 0.89-2.44 for hydrophobic statins) and of estrogen receptor-negative tumors with increasing duration of statin use (1-2.9 years: HR, 1.33; 95% CI, 0.64-2.77; 3-4.9 years: HR, 1.68; 95% CI, 0.72-3.92; >or=5 years: HR, 1.81; 95% CI, 0.75-4.36). CONCLUSION: This study does not support an association between statin use and breast cancer risk.     

Consumption of fish and meats and risk of hepatocellular carcinoma: the European Prospective Investigation into Cancer and Nutrition (EPIC)

BackgroundWhile higher intake of fish and lower consumption of red/processed meats have been suggested to play a protective role in the etiology of several cancers, prospective evidence for hepatocellular carcinoma (HCC) is limited, particularly in Western European populations.MethodsThe associations of fish and meats with HCC risk were analyzed in the EPIC cohort. Between 1992 and 2010, 191 incident HCC were identified among 477 206 participants. Baseline diet was assessed using validated dietary questionnaires. A single 24-h diet recall from a cohort subsample was used for calibration. Multivariable proportional hazard regression was utilized to estimate hazard ratios (HR) and 95% confidence intervals (CI). In a nested case–control subset (HCC = 122), HBV/HCV status and liver function biomarkers were measured.ResultsHCC risk was inversely associated with intake of total fish (per 20 g/day increase, HR = 0.83, 95% CI 0.74–0.95 and HR = 0.80, 95% CI 0.69–0.97 before and after calibration, respectively). This inverse association was also suggested after adjusting for HBV/HCV status and liver function score (per 20-g/day increase, RR = 0.86, 95% CI 0.66–1.11 and RR = 0.74, 95% CI 0.50–1.09, respectively) in a nested case–control subset. Intakes of total meats or subgroups of red/processed meats, and poultry were not associated with HCC risk.ConclusionsIn this large European cohort, total fish intake is associated with lower HCC risk.     

Diabetes,metformin and cancer risk in myotonic dystrophy type I

Myotonic dystrophy type I (DM1) is an autosomal dominant multisystem disorder characterized by myotonia and muscle weakness. Type 2 diabetes (T2D) and cancer have been shown to be part of the DM1 phenotype. Metformin, a well-established agent for the management of T2D, is thought to have cancer-preventive effects in the general population. In our study, we aimed to assess the association between T2D, metformin use and the risk of cancer in DM1 patients. We identified a cohort of 913 DM1 patients and an age-, sex- and clinic-matched cohort of 12,318 DM1-free controls from the UK Clinical Practice Research Datalink, a large primary care records database. We used Cox regression models to assess cancer risk in T2D patients who were metformin users or nonusers compared to patients without T2D. Separate analyses were conducted for DM1 patients and controls. T2D was more prevalent in DM1 than in controls (8% vs. 3%, p < 0.0001). DM1 patients with T2D, compared to those without T2D, were more likely to develop cancer (hazard ratio [HR] = 3.60, 95% confidence interval [CI] = 1.18–10.97; p = 0.02), but not if they were treated with metformin (HR = 0.43, 95% CI = 0.06–3.35; p = 0.42). Among controls, we observed no significant associations between T2D and cancer risk in either users or nonusers of Metformin (HR = 1.28, 95% CI = 0.91–1.79; p = 0.16 and HR = 1.13, 95% CI = 0.72–1.79; p = 0.59, respectively). These results show an association between T2D and cancer risk in DM1 patients and may provide new insights into the possible benefits of Metformin use in DM1.     

Hyperglycemia and chronic liver diseases on risk of hepatocellular carcinoma in Chinese patients with type 2 diabetes––National cohort of Taiwan Diabetes Study

This study examined whether glycated hemoglobin A1C (HbA1C) and chronic liver diseases are associated with hepatocellular carcinoma (HCC) risk in Type 2 diabetic patients. A retrospective cohort study consisting of 51,705 patients with Type 2 diabetes aged 30 and over enrolled in the National Diabetes Care Management Program before 2004 was used in Cox proportional hazards models. HbA1C was independently associated with HCC incidence, and multivariate‐adjusted hazard ratio (HR) of HCC was 1.20 (95% confidence interval, CI: 1.02–1.41) for patients with a level of HbA1c ≥ 9% compared with patients with a level of HbA1c <7% after multivariate adjustment. We observed a significant linear trend in HCC incidence with increasing HbA1c (p for trend = 0.02, HR = 1.07, 95% CI = 1.01–1.12 for every 1% increment in HbA1c). We observed significant HRs of HCC for patients with a level of HbA1c ≥ 9% with alcoholic liver damage, liver cirrhosis, HBV, HCV and any one of chronic liver diseases compared with patients with a level of HbA1c <9% and no counterpart comorbidity in the entire sample (HR = 8.63, 95% CI = 1.41–52.68; HR = 5.02, 95% CI = 3.10–8.12; HR = 2.53, 95% CI = 1.10–5.85; HR = 1.79, 95% CI = 1.01–3.17; and HR = 3.59, 95% CI = 2.56–5.02, respectively). Our results suggest significant joint associations of HbA1c ≥ 9% and chronic liver diseases. Lifestyle or treatment interventions such as maintaining a satisfactory glycemic control and chronic liver diseases may reduce the burden of HCC.     

Risk Profile of Hepatocellular Carcinoma Reveals Dichotomy among US Veterans

Background

Hepatocellular carcinoma (HCC) is traditionally associated with chronic liver injury resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) infection or excessive consumption of alcohol. In addition, recent evidence links HCC to diabetes.

Aims

Since these risk factors are prevalent among US veterans, we analyzedcontribution of various etiologies toHCC incidence in this population.

Methods

Clinicopathological correlates of 150 male US veterans diagnosed with HCC between 2001 and 2010 were analyzed and compared to frequency-matched (2:1) non-cancer controls in a single center.

Results

HCC was associated with cirrhosis (odds ratio [OR], 250.84; 95 % confidence interval [CI], 86.92–723.88; p?<?0.0001), chronic hepatitis B (OR, 34.30 95 % CI, 1.97–598.47; p?=?0.015), chronic hepatitis C (OR, 6.84; 95 % CI, 3.89–12.04; p?<?0.0001), alcohol use (OR, 6.76; 95 % CI, 4.35–10.52; p?<?0.0001), and smoking (OR, 1.83; 95 % CI, 1.23–2.89; p?=?0.009), but surprisingly not with diabetes. Only in a subgroup of HCC patients with no “traditional” risk factors did diabetes become a strong independent predictor of HCC when compared to HCC patients with at least one such risk factor (OR, 10.69; 95 % CI, 1.88–60.63, p?=?0.007). This subgroup was further distinguished by older age, increased prevalence of hypertension, nonsmoking, and a trend to develop noncirrhotic HCC.

Conclusions

While HCC in US veterans is overwhelmingly linked to cirrhosis due to “traditional” risk factors, it also occurs with a separate clinical profile characterized by diabetes and no evidence of cirrhosis, suggesting distinct mechanisms of hepatocarcinogenesis and needs for surveillance.     

Modest increase in risk of specific types of cancer types in type 2 diabetes mellitus patients

Most studies associated diabetes mellitus (DM) with risk of cancer have focused on the Caucasian population and only a few types of cancer. Therefore, a large and comprehensive nationwide retrospective cohort study involving an Asian population was conducted to evaluate the risk of several major types of cancer among Type 2 DM patients. The study analyzed the nationwide population‐based database from 1996 to 2009 released by the National Health Research Institute in Taiwan. Incidence and hazard ratios (HRs) were calculated for specific types of cancer. The overall risk of cancers was significantly greater in the DM cohort [N = 895,434; HR = 1.19, 95% confidence interval (CI) = 1.17–1.20], compared with non‐DM controls (N = 895,434). Several organs in the digestive and urogenital systems showed increased risk of cancer. The three highest HRs were obtained from cancers of the liver (HR = 1.78, 95% CI = 1.73–1.84), pancreatic (HR = 1.52, 95% CI = 1.40–1.65), and uterus and corpus (HR = 1.38, 95% CI = 1.22–1.55). The risk increased with age, and men with DM aged ≥75 years exhibited the highest risk (HR = 7.76, 95% CI = 7.39–8.15). Subjects with DM in this population have a modest increased risk of cancer, similar to the Caucasian population for several specific types of cancer. Old men with DM have the highest risk of cancer. Careful screening for cancer in DM patients is important for early diagnosis and effective treatment.