Dietary vitamin D and cancers of the oral cavity and esophagus.

BACKGROUND: Data on the association between vitamin D and upper digestive tract neoplasms are limited. METHODS: In two case-control studies in Italy, we examined the relation between dietary vitamin D intake and squamous cell carcinoma of the esophagus (SCCE; 304 cases) and oral/pharyngeal cancer (804 cases). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by multiple logistic regression. RESULTS: Adjusted ORs for SCCE and oral/pharyngeal cancer were 0.58 (95% CI 0.39-0.86) and 0.76 (95% CI 0.60-0.94), respectively, for the highest tertile of vitamin D intake. Using a reference group of those in the highest tertile of vitamin D who were never/former smokers, ORs were 8.7 (95% CI 4.1-18.7) for SCCE and 10.4 (95% CI 6.9-15.5) for oral/pharyngeal cancer among heavy smokers in the lowest vitamin D tertile; similarly, compared with those in the highest tertile of vitamin D who drank <3 alcoholic drinks/day, corresponding ORs were 41.9 (95% CI 13.7-128.6) for SCCE and 8.5 (95% CI 5.7-12.5) for oral/pharyngeal cancer, among heavy alcohol drinkers in the lowest vitamin D tertile. CONCLUSION: We observed inverse associations between dietary vitamin D intake and risk of SCCE and, perhaps, oral/pharyngeal cancer, which were most pronounced among heavy current smokers and heavy consumers of alcohol.

Dietary glycemic load and hepatocellular carcinoma with or without chronic hepatitis infection.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the major risk factors for hepatocellular carcinoma (HCC). The association of diabetes mellitus with HCC suggests that dietary glycemic load (GL) may influence HCC risk. We have examined the association between dietary GL and HCC. PATIENTS AND METHODS: We conducted a hospital-based case-control study in Italy in 1999-2002, including 185 HCC cases and 412 controls who answered a validated food frequency questionnaire and provided blood samples. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were computed using unconditional multiple logistic regression. RESULTS: We observed a positive association between GL and HCC overall, with an OR of 3.02 (95% CI 1.49-6.12) for the highest quintile of GL compared with the lowest and a significant trend. The OR among HCC cases with evidence of chronic infection with HBV and/or HCV was 3.25 (95% CI 1.46-7.22), while the OR among those with no evidence of infection was 2.45 (95% CI 0.69-8.64), with no significant trend. The association was not explained by the presence of cirrhosis or diabetes. CONCLUSIONS: High dietary GL is associated with increased risk for HCC. The positive association was most pronounced among HCC cases with HBV and/or HCV markers.

Proton pump inhibitors and risk of gastric cancer: a population-based cohort study.

Proton pump inhibitor (PPI) use leads to hypergastrinaemia, which has been associated with gastrointestinal neoplasia. We evaluated the association between PPI use and risk of gastric cancer using population-based health-care registers in North Jutland, Denmark, during 1990-2003. We compared incidence rates among new users of PPI (n=18,790) or histamine-2-antagonists (H2RAs) (n=17,478) and non-users of either drug. Poisson regression analysis was used to estimate incidence rate ratios (IRRs) adjusted for multiple confounders. We incorporated a 1-year lag time to address potential reverse causation. We identified 109 gastric cancer cases among PPI users and 52 cases among H2RA users. After incorporating the 1-year lag time, we observed IRRs for gastric cancer of 1.2 (95% CI: 0.8-2.0) among PPI users and 1.2 (95% CI: 0.8-1.8) among H2RA users compared with non-users. These estimates are in contrast to significant overall IRRs of 9.0 and 2.8, respectively, without the lag time. In lag time analyses, increased IRRs were observed among PPI users with the largest number of prescriptions or the longest follow-up compared with H2RA users or non-users. Although our results point to a major influence of reverse causation and confounding by indication on the association between PPI use and gastric cancer incidence, the finding of increased incidence among PPI users with most prescriptions and longest follow-up warrants further investigation.

Vitamin D intake and breast cancer risk: a case-control study in Italy.

BACKGROUND: Vitamin D has been suggested to play a protective role against several cancers, including breast cancer. PATIENTS AND METHODS: We used data from a case-control study conducted in Italy from 1991 to 1994 to study the relation between dietary intake of vitamin D and breast cancer risk. Subjects were 2569 women with incident, histologically confirmed breast cancer and 2588 hospital controls. Odds ratios (ORs) and 95% confidence intervals (CIs) according to deciles of vitamin D intake were estimated by multiple logistic regression models. RESULTS: After allowance for major risk factors for breast cancer and dietary covariates including calcium and energy intake, there was no association with vitamin D up to the seventh decile. Thereafter, the OR declined, so that the overall trend was statistically significantly inverse. The OR for subjects in the three highest deciles of consumption compared with those in the lowest ones combined was 0.79 (95% CI 0.70-0.90). Intake of vitamin D >3.57 microg or 143 IU appeared to have a protective effect against breast cancer. The inverse association was consistent across strata of menopausal status. CONCLUSIONS: This study adds to the existing evidence that vitamin D intake in inversely associated with breast cancer risk.

Formaldehyde and cancer risk: a quantitative review of cohort studies through 2006.

BACKGROUND: Occupational exposure to formaldehyde has been associated with excess risk of nasopharyngeal and selected other cancers. PATIENTS AND METHODS: We reviewed and pooled the results of cohort studies published through February 2007. RESULTS: There were 5651 deaths from all cancers observed in six cohorts of industry workers and six of professionals, with a pooled relative risk (RR) of 0.95 for industry workers and of 0.87 for professionals. Nine deaths from nasopharyngeal cancer in three cohorts of industry workers yielded a pooled RR of 1.33, which declined to 0.49 after excluding six cases from one US plant. The pooled RR for lung cancer was 1.06 in industry workers and 0.63 in professionals. Corresponding values were 1.09 and 0.96 for oral and pharyngeal, 0.92 and 1.56 for brain, 0.85 and 1.31 for all lymphatic and hematopoietic cancers, and 0.90 and 1.39 for leukemia. CONCLUSIONS: Comprehensive review of cancer in industry workers and professionals exposed to formaldehyde shows no appreciable excess risk for oral and pharyngeal, sinonasal or lung cancers. A non-significantly increased RR for nasopharyngeal cancer among industry workers is attributable to a cluster of deaths in a single plant. For brain cancer and lymphohematopoietic neoplasms there were modestly elevated risks in professionals, but not industry workers.

Flavonoids and laryngeal cancer risk in Italy.

BACKGROUND: Flavonoids may play an important role in explaining the protective effect of vegetables and fruit against cancer. PATIENTS AND METHODS: To investigate the relation between flavonoids and laryngeal cancer risk, we have applied data on the composition of foods and beverages in terms of six principal classes of flavonoids to a case-control study of laryngeal cancer conducted from 1992 to 2000 in Italy. Cases were 460 subjects with incident, histologically confirmed laryngeal cancer; controls were 1088 patients admitted for acute, non-neoplastic diseases. Odds ratios (OR) were estimated through multiple logistic regression models, including terms for sociodemographic and lifestyle factors, tobacco smoking, alcohol consumption and energy intake. RESULTS: Significant inverse relations were found for the highest versus the lowest quintile of intake for flavan-3-ols (OR = 0.64), flavanones (OR = 0.60), flavonols (OR = 0.32) and total flavonoids (OR = 0.60), although the overall trends in risk were significant only for flavanones and flavonols. No consistent associations were observed for isoflavones, anthocyanidins and flavones. The estimates did not differ substantially across strata of alcohol drinking, tobacco smoking, body mass index and education, and tended to persist even after controlling for vegetable and fruit intake. CONCLUSION: This study provides support for a beneficial effect of selected flavonoids on laryngeal cancer risk.

Outcome of peptic ulcer bleeding among users of traditional non-steroidal anti-inflammatory drugs and selective cyclo-oxygenase-2 inhibitors.

BACKGROUND: Few data exist on the impact of non-steroidal anti-inflammatory drug use on peptic ulcer outcome. AIM: To examine the 30-day mortality from peptic ulcer bleeding associated with the use of traditional non-steroidal anti-inflammatory drugs and newer selective cyclo-oxygenase-2 inhibitors. METHODS: Cohort study of patients with a first hospitalization for peptic ulcer bleeding in three Danish counties between 1991 and 2003. Data on pre-admission non-steroidal anti-inflammatory drug use, use of other ulcer-related drugs and comorbidities were obtained from population-based registries. Follow-up data on mortality were obtained from the Danish Civil Registry System. RESULTS: Of 7,232 patients hospitalized for peptic ulcer bleeding, 28% were current non-steroidal anti-inflammatory drug users. Thirty-day mortality was 11% overall, and 13% among current non-steroidal anti-inflammatory drug users. Compared with never-use, the adjusted 30-day mortality rate ratios were 1.4 (95% CI: 1.1-1.9) for current use of non-steroidal anti-inflammatory drugs alone and 1.3 (95% CI: 1.0-1.7) for current use combined with other ulcer-related drugs. For users of celecoxib, alone and in combination, adjusted mortality rate ratios were 1.4 (95% CI: 0.5-3.9) and 2.0 (95% CI: 1.2-3.5), and for users of rofecoxib, 1.2 (95% CI: 0.4-3.9) and 0.9 (95% CI: 0.5-1.6). CONCLUSION: Among patients hospitalized with peptic ulcer bleeding, use of non-steroidal anti-inflammatory drugs, including some newer cyclo-oxygenase-2 inhibitors, is associated with increased short-term mortality.

Cancer risk among users of neuroleptic medication: a population-based cohort study.

It has been suggested that neuroleptic medication may decrease cancer risk. We compared cancer risks in a population-based cohort study of 25,264 users (>or=2 prescriptions) of neuroleptic medications in the county of North Jutland, Denmark, during 1989-2002, with that of county residents who did not receive such prescriptions. Statistical analyses were based on age-standardisation and Poisson regression analysis, adjusting for age, calendar period, COPD, liver cirrhosis or alcoholism, use of NSAID, and, for breast cancer, additionally for use of hormone therapy, age at first birth, and number of children. Use of neuroleptic medications was associated with a decreased risk for rectal cancer in both women and men (adjusted IRRs of 0.61 (95% confidence interval, 0.41-0.91) and 0.82 (0.56-1.19), respectively) and for colon cancer in female users (0.78; 0.62-0.98). Some risk reduction was seen for prostate cancer (0.87; 0.69-1.08), but breast cancer risk was close to unity (0.93; 0.74-1.17). Overall, treatment with neuroleptic medications was not related to a reduced risk of cancer, but for cancers of the rectum, colon and prostate there were suggestive decreases in risk.

Risk and short-term prognosis of myocardial infarction among users of antidiabetic drugs.

Old sulphonylureas have been linked with adverse cardiovascular effects; however, data on the clinical implications are sparse. We examined the association between use of sulphonylureas and other antidiabetic drugs and the risk and case fatality rate (CFR) of myocardial infarction (MI) in a population-based case-control and follow-up study, respectively. A total of 6738 cases of first-time MI and 67,374 age- and gender-matched population controls were identified from the Hospital Discharge Registry and the Civil Registration System of North Jutland County, Denmark, in the period 1994 through 2002. Prescriptions for antidiabetic drugs before the index date were retrieved from a prescription database. We estimated odds ratios (ORs) of MI (case-control study) and 30-day CFR (follow-up study) associated with antidiabetic drug use adjusted for possible confounding factors and using nondiabetic subjects as the reference group. The risk of MI appeared higher among users of old sulphonylureas (adjusted OR, 2.07; 95% confidence interval (CI), 1.81-2.37) than among users of new sulphonylureas (adjusted OR, 1.36; 95% CI, 1.01-1.84). The adjusted ORs among users of nonsulphonylurea oral antidiabetic drugs, insulin, and patients with diabetes not receiving pharmacotherapy were 1.38 (95% CI, 0.90-2.11), 2.56 (95% CI, 2.16-3.03), and 3.51 (95% CI, 2.92-4.22), respectively. The overall 30-day CFR was 24.6%, but varied between 9.5% and 37.0% among the different categories. New sulphonylureas may be associated with a lower risk of MI than old sulphonylureas. Furthermore, the 30-day CFR may vary according to type of antidiabetic drug. These differences indicate the need for further examination of the cardiovascular safety of antidiabetic drugs.

Statins and the risk of acute pancreatitis: a population-based case-control study.

BACKGROUND: Case reports have suggested that statins may cause acute pancreatitis. AIM: To examine if statins are associated with risk of acute pancreatitis. METHODS: We identified 2576 first-time admitted cases of acute pancreatitis from hospital discharge registers in three Danish counties, and 25 817 age- and gender-matched controls from the general population. Prescriptions for statins prior to admission with acute pancreatitis or index date among controls were retrieved from prescription databases. We used conditional logistic regression analysis to estimate odds ratios for acute pancreatitis among ever (ever before), current (0-90 days before), new (first prescription in 0-90 days before) and former (>90 days, but not 0-90 days before) users of statins. RESULTS: Adjusted odds ratios for acute pancreatitis among ever, current, new and former users of statins were 1.44 (95% confidence interval: 1.115-1.80), 1.26 (95% confidence interval: 0.96-1.64), 1.01 (95% confidence interval: 0.43-2.37) and 2.02 (95% confidence interval: 1.37-2.97), respectively. There was an indication of an inverse association between the number of filled prescriptions and risk of acute pancreatitis. CONCLUSIONS: Our findings speak against a strong causative effect of statins on the risk of acute pancreatitis, and may even indicate a mild protective effect.

Parkinson's disease and other basal ganglia or movement disorders in a large nationwide cohort of Swedish welders.

INTRODUCTION: Although it has been hypothesised that metal welding and flame cutting are associated with an increased risk for Parkinson's disease due to manganese released in the welding fume, few rigorous cohort studies have evaluated this risk. METHODS: The authors examined the relation between employment as a welder and all basal ganglia and movement disorders (ICD-10, G20-26) in Sweden using nationwide and population based registers. All men recorded as welders or flame cutters (n = 49,488) in the 1960 or 1970 Swedish National Census were identified and their rates of specific basal ganglia and movement disorders between 1964 and 2003 were compared with those in an age and geographical area matched general population comparison cohort of gainfully employed men (n = 489,572). RESULTS: The overall rate for basal ganglia and movement disorders combined was similar for the welders and flame cutters compared with the general population (adjusted rate ratio (aRR) = 0.91 (95% CI 0.81 to 1.01). Similarly, the rate ratio for PD was 0.89 (95% CI 0.79 to 0.99). Adjusted rate ratios for other individual basal ganglia and movement disorders were also not significantly increased or decreased. Further analyses of Parkinson's disease by attained age, time period of follow up, geographical area of residency, and educational level revealed no significant differences between the welders and the general population. Rates for Parkinson's disease among welders in shipyards, where exposures to welding fumes are higher, were also similar to the general population (aRR = 0.95; 95% CI 0.70 to 1.28). CONCLUSION: This nationwide record linkage study offers no support for a relation between welding and Parkinson's disease or any other specific basal ganglia and movement disorders.

A cohort study of antihypertensive treatments and risk of renal cell cancer.

We studied 335,682 county residents, of whom 113,298 had been prescribed antihypertensive treatment (AHT), in the period 1989-2002 in North Jutland County, Denmark to examine the relation between different AHTs and the risk of renal cell carcinoma (RCC). An internal comparison was performed among the different classes of AHT users with users of beta blockers as the reference, in order to address potential confounding and bias. The average follow-up was 10 years (range 0-13). Use of any AHT was associated with RCC (relative rate (RR)=1.6, 95% confidence interval (CI) 1.3-1.9) compared with nonusers in the general population. Specific classes of AHTs were nonsignificantly associated with RCC, but compared with users of beta blockers, the numbers observed were close to expectation. Analyses by duration of follow-up and number of prescriptions revealed no clear trends for any antihypertensive agent and after 5-years of follow-up, the RRs for all classes of AHT decreased. The elevated RRs for RCC among users of AHTs compared with the general population are unlikely to be causal, but rather reflect confounding due to failure to control for pre-existing hypertension, and protopathic bias, due to the presence of hypertension as an early sign of kidney disease.

Cellular telephones and risk for brain tumors: a population-based, incident case-control study.

OBJECTIVE: To evaluate a possible association of glioma or meningioma with use of cellular telephones, using a nationwide population-based case-control study of incident cases of meningioma and glioma. METHODS: The authors ascertained all incident cases of glioma and meningioma diagnosed in Denmark between September 1, 2000, and August 31, 2002. They enrolled 252 persons with glioma and 175 persons with meningioma aged 20 to 69. The authors also enrolled 822 randomly sampled, population-based controls matched for age and sex. Information was obtained from personal interviews, medical records containing diagnoses, and the results of radiologic examinations. For a small number of cases and controls, the authors obtained the numbers of incoming and outgoing calls. They evaluated the memory of the respondents with the Mini-Mental State Examination and obtained data on socioeconomic factors from Statistics Denmark. RESULTS: There were no material socioeconomic differences between cases and controls or participants and non-participants. Use of cellular telephone was associated with a low risk for high-grade glioma (OR, 0.58; 95% CI, 0.37 to 0.90). The risk estimates were closer to unity for low-grade glioma (1.08; 0.58 to 2.00) and meningioma (1.00; 0.54 to 1.28). CONCLUSION: The results do not support an association between use of cellular telephones and risk for glioma or meningioma.

Hormone use for menopausal symptoms and risk of breast cancer. A Danish cohort study.

Numerous studies and meta-analyses have shown that hormone replacement therapy (HRT) for menopausal symptoms increases the risk of developing breast cancer, estimated to be 2.3% for each year of use. The influence of different oestrogen-progestin regimens has still not been fully evaluated. Using longitudinal data from the population-based prescription database of the county of North Jutland, Denmark, and the Danish Cancer Registry, we examined the risk of developing breast cancer in relation to HRT in a cohort of 78,380 women aged 40-67 years from 1989 to 2002. A total of 1462 cases of breast cancer were identified during a mean follow-up of 10 years. Use of HRT did not increase the risk of breast cancer in women aged 40-49 years. Restricting the cohort to 48,812 women aged 50 years or more at entry, of whom 15 631 were HRT users, we found an increased risk associated with current use of HRT (relative risk 1.61, 95% confidence interval 1.38-1.88). The risk increased with increasing duration of use and decreased with time since last HRT prescription, reaching unity after 5 years. No material risk difference was observed among the various HRT-regimens. This population-based cohort study provides further confirmation that HRT increases the risk of developing breast cancer in women aged 50 years or more.

Use of antibiotics and risk of breast cancer: a population-based case-control study.

We examined the use of antibiotics among 2728 women with a first diagnosis of breast cancer during 1994-2003, and 27 280 population controls in North Jutland County, Denmark, based on hospital discharge diagnoses, prescription use from 1989 to 2002, and population registry data. We found no increased relative risk of breast cancer associated with use compared with nonuse. The odds ratio for breast cancer associated with more than 10 prescriptions for antibiotics was 1.00 (95% CI 0.86 -1.15). Relative risks were similar for different classes of antibiotics. A subanalysis based on cases and controls younger than 70 years of age, with data on first birth and number of children, showed similar risk estimates even after adjustment for age at first birth and parity. In our study, use of antibiotics was not associated with an increased risk of breast cancer.

Atypical cancer pattern in patients with Parkinson's disease.

Among 14,088 patients, with a primary diagnosis of Parkinson's disease during the period 1977-98 identified from the National Register of Patients, 1282 cancers were subsequently recorded in the Danish Cancer Registry, compared with 1464 expected, with a standardised incidence ratio (SIR) of 0.88 (95% confidence interval (CI), 0.8-0.9). Significantly reduced risks were found for smoking-related cancers, for example, cancers of the lung (SIR, 0.38), larynx (0.47) and urinary bladder (0.52), although moderate reductions in risk were also seen for several nonsmoking-related cancers. In contrast, increased risks were seen for malignant melanoma (SIR, 1.95; 95% CI, 1.4-2.6), nonmelanocytic skin cancer (1.25; 1.1-1.4) and breast cancer (1.24; 1.0-1.5). The observed cancer pattern supports the hypothesis that constituents of tobacco smoke inhibit or delay the development of Parkinson's disease, but a low smoking prevalence appears to be only part of the explanation for the decreased cancer incidence. The increased relative risks of melanoma and nonmelanoma skin cancer are not likely to be artefactual, but further investigations of potential mechanisms are warranted.

Antipolymer antibodies in Danish fibromyalgia patients.

OBJECTIVE: To use a new immunologic assay to investigate antipolymer antibody (APA) levels in women with fibromyalgia (FM). METHODS: The study population consisted of 35 patients with FM and 129 controls. The controls were selected based on a prior history of breast surgery and the presence or absence of a prior hospital diagnosis of soft tissue rheumatism. Study subjects underwent blood sampling, including tests for antinuclear antibodies (ANA) and APA, a clinical examination, and an interview focusing on rheumatic complaints and self-reported disability. The severity of rheumatic symptoms/signs was scored from 1 (= none) to 5 (= severe) based on the clinical examination and the interview. RESULTS: FM patients in this study represented a broad spectrum of disease severity, with the majority having mild symptoms. FM patients had a higher symptom severity and myalgic scores than controls (p < 0.001 for both variables). Adjusting for symptom severity, a weak positive association between APA levels and FM was observed (p = 0.08). The APA level was inversely associated with age, i.e., decreasing APA levels were seen with increasing age (p = 0.008). CONCLUSION: FM patients tended to have slightly higher APA levels than controls when adjusted for symptom severity. APA levels declined with age, a finding that has not been reported previously. The APA test and its clinical relevance should be evaluated in future studies.

COX-2-selective inhibitors and the risk of upper gastrointestinal bleeding in high-risk patients with previous gastrointestinal diseases: a population-based case-control study.

BACKGROUND: Clinical trials have suggested that cyclo-oxygenase-2-selective inhibitors are associated with a lower risk of upper gastrointestinal bleeding than are non-selective, non-aspirin, non-steroidal anti-inflammatory drugs. This has not yet been confirmed in studies of patients with an increased susceptibility to upper gastrointestinal bleeding. AIM: To examine the risk of upper gastrointestinal bleeding in high-risk patients who filled prescriptions for cyclo-oxygenase-2 inhibitors or other non-steroidal anti-inflammatory drugs. METHODS: A population-based case-control study was performed in the Danish county of North Jutland from 1 January 2000 to 31 December 2002. From the County Hospital Discharge Registry and the Civil Registration System, we identified incident cases with upper gastrointestinal bleeding (n = 780) and randomly selected controls (n = 2906), respectively. All cases and controls had previous gastrointestinal diseases. Data on drug exposure were obtained from the countywide Prescription Database. RESULTS: Thirty-five cases (4.5%) filled prescriptions for cyclo-oxygenase-2 inhibitors within 30 days of the date of upper gastrointestinal bleeding, compared with 79 controls (2.7%). Adjusted odds ratios for upper gastrointestinal bleeding according to prescription for celecoxib, rofecoxib and non-steroidal anti-inflammatory drugs were 1.3 [95% confidence interval (CI), 0.7-2.8], 2.1 (95% CI, 1.2-3.5) and 3.3 (95% CI, 2.4-4.4), respectively. CONCLUSIONS: In patients with increased susceptibility to gastrointestinal adverse events, a lower risk of upper gastrointestinal bleeding was observed in users of cyclo-oxygenase-2 inhibitors compared with users of other non-aspirin, non-steroidal anti-inflammatory drugs.

Occupational exposure to vinyl chloride and cancer risk: a review of the epidemiologic literature.

Occupational exposure to vinyl chloride (VC) is causally related to liver angiosarcoma, whereas there is inconsistent epidemiologic evidence for other neoplasms. Two pooled analyses of worker cohorts from 56 plants in North America and Europe provide the most comprehensive and updated data on cancer risk among workers exposed to VC. These included over 22,000 workers, with a total of 640,000 person-years of observation, followed-up for up to 50 years. Overall, a total of 1,778 cancer deaths were observed versus 1,829.46 expected, corresponding to a standardized mortality ratio (SMR) of 0.97 (95% confidence interval (CI)=0.93-1.02). Excluding 71 confirmed angiosarcomas, there were 60 deaths from liver cancers versus 44.35 expected (SMR=1.35, 95% CI=1.03-1.74). Lung and laryngeal cancer mortality were significantly lower than expected (SMR=0.88 and 0.59, respectively). The SMRs for soft tissue sarcoma, brain, lymphoid and haematopoietic system cancers were not materially different from unity. Thus, the aggregate data from over 20,000 VC workers in North America and Europe exclude any excess mortality from lung, laryngeal, soft tissue sarcoma, brain, lymphoid and haematopoietic neoplasms. There appears to be a slight excess of liver cancer other than angiosarcoma, which is difficult to interpret and is likely due to residual misclassification of angiosarcomas.