Drugs Associated with Hepatotoxicity and their Reporting Frequency of Liver Adverse Events in VigiBase (TM) Unified List Based on International Collaborative Work

BACKGROUND Challenges exist in the clinical diagnosis of drug-induced liver injury (DILI) and in obtaining information on hepatotoxicity in humans. OBJECTIVE (i) To develop a unified list that combines drugs incriminated in well vetted or adjudicated DILI cases from many recognized sources and drugs that have been subjected to serious regulatory actions due to hepatotoxicity; and (ii) to supplement the drug list with data on reporting frequencies of liver events in the WHO individual case safety report database (VigiBase). DATA SOURCES AND EXTRACTION (i) Drugs identified as causes of DILI at three major DILI registries; (ii) drugs identified as causes of drug-induced acute liver failure (ALF) in six different data sources, including major ALF registries and previously published ALF studies; and (iii) drugs identified as being subjected to serious governmental regulatory actions due to their hepatotoxicity in Europe or the US were collected. The reporting frequency of adverse events was determined using VigiBase, computed as Empirical Bayes Geometric Mean (EBGM) with 90% confidence interval for two customized terms, 'overall liver injury' and 'ALF'. EBGM of >or=2 was considered a disproportional increase in reporting frequency. The identified drugs were then characterized in terms of regional divergence, published case reports, serious regulatory actions, and reporting frequency of 'overall liver injury' and 'ALF' calculated from VigiBase. DATA SYNTHESIS After excluding herbs, supplements and alternative medicines, a total of 385 individual drugs were identified; 319 drugs were identified in the three DILI registries, 107 from the six ALF registries (or studies) and 47 drugs that were subjected to suspension or withdrawal in the US or Europe due to their hepatotoxicity. The identified drugs varied significantly between Spain, the US and Sweden. Of the 319 drugs identified in the DILI registries of adjudicated cases, 93.4% were found in published case reports, 1.9% were suspended or withdrawn due to hepatotoxicity and 25.7% were also identified in the ALF registries/studies. In VigiBase, 30.4% of the 319 drugs were associated with disproportionally higher reporting frequency of 'overall liver injury' and 83.1% were associated with at least one reported case of ALF. CONCLUSIONS This newly developed list of drugs associated with hepatotoxicity and the multifaceted analysis on hepatotoxicity will aid in causality assessment and clinical diagnosis of DILI and will provide a basis for further characterization of hepatotoxicity.

Long-term consequences of uninephrectomy in male and female rats.

We investigated the effects of uninephrectomy (UNX) in 6-week-old male and female rats on blood pressure (BP), renal sodium handling, salt sensitivity, oxidative stress, and renal injury over 18 months postsurgery, studying control sham-operated and UNX-operated rats at 6, 12, and 18 months postsurgery, evaluating their renal sodium handling, BP, urinary isoprostanes, N-acetyl-β-D-glucosaminidase, and proteinuria before and after a 2-week high-salt intake period. At 18 months, plasma variables were measured and kidney samples were taken for the analysis of renal morphology and tissue variables. BP was increased at 6 months in male UNX rats versus controls and at 12 and 18 months in both male and female UNX rats and was increased in male versus female UNX groups at 18 months. UNX did not affect water and sodium excretion under basal conditions and after the different test in male and female rats at different ages. However, the renal function curve was shifted to the right in both male and female UNX rats. High-salt intake increased BP in both UNX groups at 6, 12, and 18 months and in the female control group at 18 months, and it increased proteinuria, N-acetyl-β-D-glucosaminidase, and isoprostanes in both UNX groups throughout the study. Renal lesions at 18 months were more severe in male versus female UNX rats. In summary, long-term UNX increased the BP, creatinine, proteinuria, pathological signs of renal injury, and salt sensitivity. Earlier BP elevation was observed and morphological lesions were more severe in male than in female UNX rats.

Perioperative intravenous iron; an upfront therapy for treating anaemia and reducing transfusion requirements.

Perioperative anaemia, with iron deficiency being its leading cause, is a frequent condition among surgical patients, and has been linked to increased postoperative morbidity and mortality, and decreased quality of life. Postoperative anaemia is even more frequent and is mainly caused by perioperative blood loss, aggravated by inflammation-induced blunting of erythropoiesis. Allogenic transfusion is commonly used for treating acute perioperative anaemia, but it also increases the rate of morbidity and mortality in surgical and critically ill patients. Thus, overall concerns about adverse effects of both preoperative anaemia and allogeneic transfusion have prompted the review of transfusion practice and the search for safer and more biologically rational treatment options. In this paper, the role of intravenous iron therapy (mostly with iron sucrose and ferric carboxymaltose), as a safe and efficacious tool for treating anaemia and reducing transfusion requirements in surgical patients, as well as in other medical areas, has been reviewed. From the analysis of published data and despite the lack of high quality evidence in some areas, it seems fair to conclude that perioperative intravenous iron administration, with or without erythropoiesis stimulating agents, is safe, results in lower transfusion requirements and hastens recovery from postoperative anaemia. In addition, some studies have reported decreased rates of postoperative infection and mortality, and shorter length of hospital stay in surgical patients receiving intravenous iron.

Iodine intakes of 100-300 μg/d do not modify thyroid function and have modest anti-inflammatory effects.

Little information is available as to whether doses of iodide similar to those recommended in clinical practice for the prevention of iodine deficiency in pregnant women affect thyroid function. The aim of the present study was to analyse whether doses of iodide can affect thyroid function in adults, and evaluate its effect on plasma markers of oxidative stress, inflammation and acute-phase proteins. A total of thirty healthy volunteers (ten men and twenty women) with normal thyroid function were randomly assigned to three groups (n 10). Each group received a daily dose of 100, 200 or 300 μg of iodide in the form of KI for 6 months. Free tetraiodothyronine (FT4) levels at day 60 of the study were higher in the groups treated with 200 and 300 μg (P = 0·01), and correlated with the increase in urinary iodine (r 0·50, P = 0·007). This correlation lost its significance after adjustment for the baseline FT4. The baseline urinary iodine and FT4 correlated positively with the baseline glutathione peroxidase. On day 60, urinary iodine correlated with C-reactive protein (r 0·461, P = 0·018), and free triiodothyronine correlated with IL-6 (r - 0·429, P = 0·025). On day 60, the changes produced in urinary iodine correlated significantly with the changes produced in α1-antitrypsin (r 0·475, P = 0·014) and ceruloplasmin (r 0·599, P = 0·001). The changes in thyroid-stimulating hormone correlated significantly with the changes in α1-antitrypsin (r - 0·521, P = 0·005) and ceruloplasmin (r - 0·459, P = 0·016). In conclusion, the administration of an iodide supplement between 100 and 300 μg/d did not modify thyroid function in a population with adequate iodine intake. The results also showed a slight anti-inflammatory and antioxidative action of iodide.

Differential outcome of concurrent radiotherapy plus epidermal growth factor receptor inhibitors versus radiotherapy plus cisplatin in patients with human papillomavirus-related head and neck cancer.

BACKGROUND Human papillomavirus (HPV)-related head and neck cancer has been associated with an improved prognosis in patients treated with radiotherapy (RT) +/- chemotherapy (CT); however, RT combined with epidermal growth factor receptor (EGFR) inhibitors has not been fully studied in this group of patients. METHODS Immunohistochemical expression of p16 and PCR of HPV16 DNA were retrospectively analyzed in tumor blocks from 108 stage III/IV head and neck cancer patients treated with RT+CT (56) or RT+EGFR inhibitors (52). Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. RESULTS DNA of HPV16 was found in 12 of 108 tumors (11%) and p16 positivity in 18 tumors (17%), with similar rates in both arms of treatment. After a median follow-up time of 35 months (range 6-135), p16-positive patients treated with RT+EGFR inhibitors showed improved survival compared with those treated with RT+CT (2-year OS 88% vs. 60%, HR 0.18; 95% CI 0.04 to 0.88; p = 0.01; and 2-year DFS 75% vs. 47%, HR 0.17; 95% CI 0.03 to 0.8; p = 0.01). However, no differences were observed in p16-negative patients (2-year OS 56% vs. 53%, HR 0.97; 95% CI 0.55 to 1.7; p = 0.9; and 2-year DFS 43% vs. 45%, HR 0.99; 95% CI 0.57 to 1.7; p = 0.9). CONCLUSIONS This is the first study to show that p16-positive patients may benefit more from RT+EGFR inhibitors than conventional RT+CT. These results are hypothesis-generating and should be confirmed in prospective trials.

Association between magnesium-deficient status and anthropometric and clinical-nutritional parameters in posmenopausal women.

Background: During menopause occurs weight gain and bone loss occurs due to the hormone decline during this period and other factors such as nutrition. Magnesium deficiency suggests a risk factor for obesity and osteoporosis. OBJECTIVE: To evaluate the clinical and nutritional magnesium status in a population of postmenopausal women, assessing intake and serum levels of magnesium in the study population and correlation with anthropometric parameters such as body mass index(BMI) and body fat, and biochemical parameters associated. SUBJECTS AND METHOD: The study involved 78 healthy women aged 44-76, with postmenopausal status, from the province of Grenade, Spain. The sample was divided into two age groups: group1, aged < 58, and group 2 aged >/= 58. Anthropometric parameters were recorded and nutritional intake was assessed by 72-hour recall, getting the RDAs through Nutriber(R) program. To assess the biochemical parameters was performed a blood sample was taken. Magnesium was analyzed by flame atomic absorption spectrophotometry (FAAS) in erythrocyte and plasma wet-mineralized samples. RESULTS: Our results show that 37.85% of the total subjects have an overweight status. Magnesium intake found in our population is insufficient in 36% of women,while plasma magnesium deficiency corresponds to 23% of the population and 72% of women have deficient levels of magnesium in erythrocyte. Positive correlations were found between magnesium intake and dietary intake of calcium, of phosphorus,and with prealbumin plasma levels, as well as with a lower waist / hip ratio Magnesium levels in erythrocyte were correlated with lower triglycerides and urea values. CONCLUSION: It is important to control and monitor the nutritional status of magnesium in postmenopausal women to prevent nutritional alterations and possible clinical and chronic degenerative diseases associated with magnesium deficiency and with menopause.

Iron metabolism, inflammation and anemia in critically ill patients. A cross-sectional study.

INTRODUCTION For critically patients, enteral immunonutrition results in notable reductions in infections and in length of stay in hospital, but not on mortality, raising the question as to whether this relate to the heterogeneous nature of critically ill patients or to the absence of the altered absorption of specific nutrients within the immunonutrient mix (e.g. iron). Immune-associated functional iron deficiency (FID) is not only one of the many causes or anaemia in the critically ill, but also a cause of inappropriate immune response, leading to a longer duration of episodes of systemic inflammatory response syndrome and poor outcome. OBJECTIVE This prospective cross-sectional study was undertaken to assess the prevalence of FID in critically ill patients during their stay in intensive care (ICU) in order to find the more appropriate population of patients that can benefit from iron therapy. METHOD Full blood cell counts, including reticulocytes (RETIC), serum iron (SI), transferring levels (TRF) and saturation (satTRF), serum TFR receptor (sTfR), ferritin (FRT) and C-reactive protein (CRP) were measured in venous blood samples from 131 random patients admitted to the ICU for at least 24 h (Length of ICU stay, LIS; min: 1 day; max: 38 days). RESULTS Anaemia (Hb < 12 g/dL) was present in 76% of the patients (Hb < 10 g/dL in 33%), hypoferremia (SI < 45 microg/dl) in 69%; satTRF < 20% in 53%; FRT < 100 ng/mL in 23%; sTfR > 2.3 mg/dL in 13%; and CRP > 0.5 mg/dL in 88%. Statistically significant correlations (r of Pearson; *p < 0.05, **p < 0.01) were obtained for serum CRP levels and WBC**, Hb*, TRF**, satTRF*, and FRT**. There was also a strong correlation between TRF and FRT (-0.650**), but not between FRT and satTRF or SI. LIS correlated with Hb*, CRP**, TRF*, satTRF* and FRT**. CONCLUSIONS A large proportion of critically ill patients admitted to the ICU presented the typical functional iron deficiency (FID) of acute inflammation-related anaemia (AIRA). This FID correlates with the inflammatory status and the length of stay at the ICU. However, 21% of the ICU patients with AIRA had an associated real iron deficiency (satTRF < 20; FRT < 100 and sTfR > 2.3). Since oral supplementation of iron seems to be ineffective, all these patients might benefit of iv iron therapy for correction of real or functional iron deficiency, which in turn might help to ameliorate their inflammatory status.

Acute haematogenous prosthetic joint infection: prospective evaluation of medical and surgical management

The optimum treatment for prosthetic joint infections has not been clearly defined. We report our experience of the management of acute haematogenous prosthetic joint infection (AHPJI) in patients during a 3-year prospective study in nine Spanish hospitals. Fifty patients, of whom 30 (60%) were female, with a median age of 76 years, were diagnosed with AHPJI. The median infection-free period following joint replacement was 4.9 years. Symptoms were acute in all cases. A distant previous infection and/or bacteraemia were identified in 48%. The aetiology was as follows: Staphylococcus aureus, 19; Streptococcus spp., 14; Gram-negative bacilli, 12; anaerobes, two; and mixed infections, three. Thirty-four (68%) patients were treated with a conservative surgical approach (CSA) with implant retention, and 16 had prosthesis removal. At 2-year follow-up, 24 (48%) were cured, seven (14%) had relapsed, seven (14%) had died, five (10%) had persistent infection, five had re-infection, and two had an unknown evolution. Overall, the treatment failure rates were 57.8% in staphylococcal infections and 14.3% in streptococcal infections. There were no failures in patients with Gram-negative bacillary. By multivariate analysis, CSA was the only factor independently associated with treatment failure (OR 11.6; 95% CI 1.29-104.8). We were unable to identify any factors predicting treatment failure in CSA patients, although a Gram-negative bacillary aetiology was a protective factor. These data suggest that although conservative surgery was the only factor independently associated with treatment failure, it could be the first therapeutic choice for the management of Gram-negative bacillary and streptococcal AHPJI, and for some cases with acute S. aureus infections.

Effect of a specific supplement enriched with n-3 polyunsaturated fatty acids on markers of inflammation, oxidative stress and metabolic status of ear, nose and throat cancer patients.

Malnutrition affects 40-50% of patients with ear, nose and throat (ENT) cancer. The aim of this study was to assess changes induced by a specific nutritional supplement enriched with n-3 polyunsaturated fatty acids, fiber and greater amounts of proteins and electrolytes, as compared with a standard nutritional supplement, on markers of inflammation, oxidative stress and metabolic status of ENT cancer patients undergoing radiotherapy (RT). Fourteen days after starting RT, 26 patients were randomly allocated to one of two groups, 13 supplemented with Prosure, an oncologic formula enriched with n-3 polyunsaturated fatty acids, fiber and greater amounts of proteins and electrolytes (specific supplement), and 13 supplemented with Standard-Isosource (standard supplement). Patients were evaluated before RT, and 14, 28 and 90 days after starting RT. The results showed that there were no significant differences between the groups, but greater changes were observed in the standard supplement group, such as a decline in body mass index (BMI), reductions in hematocrit, erythrocyte, eosinophil and albumin levels, and a rise in creatinine and urea levels. We concluded that metabolic, inflammatory and oxidative stress parameters were altered during RT, and began to normalize at the end of the study. Patients supplemented with Prosure showed an earlier normalization of these parameters, with more favorable changes in oxidative stress markers and a more balanced evolution, although the difference was not significant.

Long-term effects of varying consumption of ω3 fatty acids in ear, nose and throat cancer patients: assessment 1 year after radiotherapy.

Abstract A prospective 1-year follow-up study in ear, nose, and throat (ENT) cancer patients was carried out one year after radiotherapy to assess the effect of varying consumption of ω3 fatty acid according to whether they consumed more or less than the 50th percentile of ω3 fatty acids. Clinical, analytical, inflammatory (CRP and IL-6), and oxidative variables (TAC, GPx, GST, and SOD) were evaluated. The study comprised 31 patients (87.1% men), with a mean age of 61.3 ± 9.1 years. Hematological variables showed significant differences in the patients with a lower consumption of ω3 fatty acids. A lower mortality and longer survival were found in the group with ω3 fatty acid consumption ≥50th percentile but the differences were not significant. No significant difference was reached in toxicity, inflammation, and oxidative stress markers. The group with ω3 fatty acid consumption <50th percentile significantly experienced more hematological and immune changes.

Spatial analysis of the relationship between mortality from cardiovascular and cerebrovascular disease and drinking water hardness.

Previously published scientific papers have reported a negative correlation between drinking water hardness and cardiovascular mortality. Some ecologic and case-control studies suggest the protective effect of calcium and magnesium concentration in drinking water. In this article we present an analysis of this protective relationship in 538 municipalities of Comunidad Valenciana (Spain) from 1991-1998. We used the Spanish version of the Rapid Inquiry Facility (RIF) developed under the European Environment and Health Information System (EUROHEIS) research project. The strategy of analysis used in our study conforms to the exploratory nature of the RIF that is used as a tool to obtain quick and flexible insight into epidemiologic surveillance problems. This article describes the use of the RIF to explore possible associations between disease indicators and environmental factors. We used exposure analysis to assess the effect of both protective factors--calcium and magnesium--on mortality from cerebrovascular (ICD-9 430-438) and ischemic heart (ICD-9 410-414) diseases. This study provides statistical evidence of the relationship between mortality from cardiovascular diseases and hardness of drinking water. This relationship is stronger in cerebrovascular disease than in ischemic heart disease, is more pronounced for women than for men, and is more apparent with magnesium than with calcium concentration levels. Nevertheless, the protective nature of these two factors is not clearly established. Our results suggest the possibility of protectiveness but cannot be claimed as conclusive. The weak effects of these covariates make it difficult to separate them from the influence of socioeconomic and environmental factors. We have also performed disease mapping of standardized mortality ratios to detect clusters of municipalities with high risk. Further standardization by levels of calcium and magnesium in drinking water shows changes in the maps when we remove the effect of these covariates.

Regulation of cell death receptor S-nitrosylation and apoptotic signaling by Sorafenib in hepatoblastoma cells.

Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.

Expression of smoothelin and smooth muscle actin in the skin.

INTRODUCTION: Smoothelin is a cytoskeletal protein of differentiated smooth muscle cells with contractile capacity, distinguishing it from other smooth muscle proteins, such as smooth muscle actin (SMA). OBJECTIVE: To evaluate the expression of smoothelin and SMA in the skin in order to establish specific localizations of smoothelin in smooth muscle cells with high contractile capacity and in the epithelial component of cutaneous adnexal structures. Methods: Immunohistochemical analysis (smoothelin and SMA) was performed in 18 patients with normal skin. RESULTS: SMA was expressed by the vascular structures of superficial, deep, intermediate and adventitial plexuses, whereas smoothelin was specifically expressed in the cytoplasm of smooth muscle cells of the deepest vascular plexus and in no other plexus of the dermis. The hair erector muscle showed intense expression of smoothelin and SMA. Cells with nuclear expression of smoothelin and cytoplasmic expression of SMA were observed in the outer root sheath of the inferior portion of the hair follicles and intense cytoplasmic expression in cells of the dermal sheath to SMA. CONCLUSIONS: We report the first study of smoothelin expression in normal skin, which differentiates the superficial vascular plexus from the deep. The deep plexus comprises vessels with high contractile capacity, which is important for understanding dermal hemodynamics in normal skin and pathological processes. We suggest that the function of smoothelin in the outer root sheath may be to enhance the function of SMA, which has been related to mechanical stress. Smoothelin has not been studied in cutaneous pathology; however we believe it may be a marker specific for the diagnosis of leiomyomas and leiomyosarcomas of the skin. Also, smoothelin could differentiate arteriovenous malformations of cavernous hemangioma of the skin

Polymorphisms of CD16A and CD32 Fcgamma receptors and circulating immune complexes in Meniere's disease: a case-control study.

BACKGROUND: Autoimmune diseases with elevated circulating autoantibodies drive tissue damage and the onset of disease. The Fcγ receptors bind IgG subtypes modulating the clearance of circulating immune complexes (CIC). The inner ear damage in Ménière's disease (MD) could be mediated by an immune response driven by CIC. We examined single-nucleotide polymorphism (SNPs) in the CD16A and CD32 genes in patients with MD which may determine a Fcγ receptor with lower binding to CIC. METHODS: The functional CD16A (FcγRIIIa*559A > C, rs396991) and CD32A (FcγRIIa*519A > G, rs1801274) SNPs were analyzed using PCR-based TaqMan Genotyping Assay in two cohorts of 156 mediterranean and 112 Galicia patients in a case-control study. Data were analyzed by χ2 with Fisher's exact test and Cochran-Armitage trend test (CATT). CIC were measured by ELISA for C1q-binding CIC. RESULTS: Elevated CIC were found in 7% of patients with MD during the intercrisis period. No differences were found in the allelic frequency for rs396991 or rs1801274 in controls subjects when they were compared with patients with MD from the same geographic area. However, the frequency of AA and AC genotypes of CD16A (rs396991) differed among mediterranean and Galicia controls (Fisher's test, corrected p = 6.9 × 10-4 for AA; corrected p = 0.02 for AC). Although genotype AC of the CD16A receptor was significantly more frequent in mediterranean controls than in patients, [Fisher's test corrected p = 0.02; OR = 0.63 (0.44-0.91)], a genetic additive effect for the allele C was not observed (CATT, p = 0.23). Moreover, no differences were found in genotype frequencies for rs396991 between patients with MD and controls from Galicia (CATT, p = 0.14). The allelic frequency of CD32 (rs1801274) was not different between patients and controls either in mediterranean (p = 0.51) or Galicia population (p = 0.11). CONCLUSIONS: Elevated CIC are not found in most of patients with MD. Functional polymorphisms of CD16A and CD32 genes are not associated with onset of MD.

Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition

Objective To examine the association between serum concentrations of total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B and the incidence of colorectal cancer (CRC). Design Nested case–control study. Setting The study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort of more than 520 000 participants from 10 western European countries. Participants 1238 cases of incident CRC, which developed after enrolment into the cohort, were matched with 1238 controls for age, sex, centre, follow-up time, time of blood collection and fasting status. Main outcome measures Serum concentrations were quantitatively determined by colorimetric and turbidimetric methods. Dietary and lifestyle data were obtained from questionnaires. Conditional logistic regression models were used to estimate incidence rate ratios (RRs) and 95% CIs which were adjusted for height, weight, smoking habits, physical activity, education, consumption of fruit, vegetables, meat, fish, alcohol, fibre and energy. Results After adjustments, the concentrations of HDL and apoA were inversely associated with the risk of colon cancer (RR for 1 SD increase of 16.6 mg/dl in HDL and 32.0 mg/dl in apoA of 0.78 (95% CI 0.68 to 0.89) and 0.82 (95% CI 0.72 to 0.94), respectively). No association was observed with the risk of rectal cancer. Additional adjustment for biomarkers of systemic inflammation, insulin resistance and oxidative stress or exclusion of the first 2 years of follow-up did not influence the association between HDL and risk of colon cancer. Conclusions These findings show that high concentrations of serum HDL are associated with a decreased risk of colon cancer. The mechanism behind this association needs further elucidation.