Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis.

BACKGROUND: Alcohol is a risk factor for cancer of the oral cavity, pharynx, oesophagus, colorectum, liver, larynx and female breast, whereas its impact on other cancers remains controversial. METHODS: We investigated the effect of alcohol on 23 cancer types through a meta-analytic approach. We used dose-response meta-regression models and investigated potential sources of heterogeneity. RESULTS: A total of 572 studies, including 486 538 cancer cases, were identified. Relative risks (RRs) for heavy drinkers compared with nondrinkers and occasional drinkers were 5.13 for oral and pharyngeal cancer, 4.95 for oesophageal squamous cell carcinoma, 1.44 for colorectal, 2.65 for laryngeal and 1.61 for breast cancer; for those neoplasms there was a clear dose-risk relationship. Heavy drinkers also had a significantly higher risk of cancer of the stomach (RR 1.21), liver (2.07), gallbladder (2.64), pancreas (1.19) and lung (1.15). There was indication of a positive association between alcohol consumption and risk of melanoma and prostate cancer. Alcohol consumption and risk of Hodgkin's and Non-Hodgkin's lymphomas were inversely associated. CONCLUSIONS: Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma.

Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study.

BACKGROUND: Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations. METHODS: In 486,799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes. RESULTS: Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11. CONCLUSIONS: Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.

Light alcohol drinking and cancer: a meta-analysis.

BACKGROUND: There is convincing evidence that alcohol consumption increases the risk of cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx. Most of the data derive from studies that focused on the effect of moderate/high alcohol intakes, while little is known about light alcohol drinking (up to 1 drink/day). PATIENTS AND METHODS: We evaluated the association between light drinking and cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx, through a meta-analytic approach. We searched epidemiological studies using PubMed, ISI Web of Science and EMBASE, published before December 2010. RESULTS: We included 222 articles comprising ∼92 000 light drinkers and 60 000 non-drinkers with cancer. Light drinking was associated with the risk of oropharyngeal cancer [relative risk, RR = 1.17; 95% confidence interval (CI) 1.06-1.29], esophageal squamous cell carcinoma (SCC) (RR = 1.30; 95% CI 1.09-1.56) and female breast cancer (RR = 1.05; 95% CI 1.02-1.08). We estimated that ∼5000 deaths from oropharyngeal cancer, 24 000 from esophageal SCC and 5000 from breast cancer were attributable to light drinking in 2004 worldwide. No association was found for colorectum, liver and larynx tumors. CONCLUSIONS: Light drinking increases the risk of cancer of oral cavity and pharynx, esophagus and female breast.

Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort.

BACKGROUND: Evidence on associations between self-reported diabetes mellitus, diabetes duration, age at diabetes diagnosis, insulin treatment, and risk of biliary tract cancer (BTC) and hepatocellular carcinoma (HCC), independent of general and abdominal obesity is scarce. PATIENTS AND METHODS: We conducted a prospective analysis in the EPIC-cohort study among 363 426 participants with self-reported diabetes data. Multivariable adjusted relative risks and 95% confidence intervals were estimated from Cox regression models. In a nested case-control subset, analyses were carried out in HCV/HBV-negative individuals. RESULTS: During 8.5 years of follow-up, 204 BTC cases [including 75 gallbladder cancer (GBC) cases], and 176 HCC cases were identified. Independent of body mass index and waist-to-height ratio diabetes status was associated with higher risk of BTC and HCC [1.77 (1.00-3.13) and 2.17 (1.36-3.47)]. For BTC, the risk seemed to be higher in participants with shorter diabetes duration and those not treated with insulin. Regarding cancer subsites, diabetes was only associated with GBC [2.72 (1.17-6.31)]. The risk for HCC was particularly higher in participants treated with insulin. The results were not appreciably different in HCV/HBV-negative individuals. CONCLUSION(S): This study supports the hypothesis that diabetes is a risk factor for BTC (particularly GBC) and HCC. Further research is required to establish whether diabetes treatment or duration is associated with these cancers.

Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western Europeans.

BACKGROUND: The type and quantity of dietary carbohydrate as quantified by glycemic index (GI) and glycemic load (GL), and dietary fiber may influence the risk of liver and biliary tract cancers, but convincing evidence is lacking. PATIENTS AND METHODS: The association between dietary GI/GL and carbohydrate intake with hepatocellular carcinoma (HCC; N = 191), intrahepatic bile duct (IBD; N = 66), and biliary tract (N = 236) cancer risk was investigated in 477 206 participants of the European Prospective Investigation into Cancer and Nutrition cohort. Dietary intake was assessed by country-specific, validated dietary questionnaires. Hazard ratios and 95% confidence intervals were estimated from proportional hazard models. HBV/HCV status was measured in a nested case-control subset. RESULTS: Higher dietary GI, GL, or increased intake of total carbohydrate was not associated with liver or biliary tract cancer risk. For HCC, divergent risk estimates were observed for total sugar = 1.43 (1.17-1.74) per 50 g/day, total starch = 0.70 (0.55-0.90) per 50 g/day, and total dietary fiber = 0.70 (0.52-0.93) per 10 g/day. The findings for dietary fiber were confirmed among HBV/HCV-free participants [0.48 (0.23-1.01)]. Similar associations were observed for IBD [dietary fiber = 0.59 (0.37-0.99) per 10 g/day], but not biliary tract cancer. CONCLUSIONS: Findings suggest that higher consumption of dietary fiber and lower consumption of total sugars are associated with lower HCC risk. In addition, high dietary fiber intake could be associated with lower IBD cancer risk.

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

BACKGROUND: While 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. METHODS: The 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. RESULTS: HCC 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. CONCLUSIONS: In this large European cohort, total fish intake is associated with lower HCC risk.

A meta-analysis of alcohol drinking and oral and pharyngeal cancers: results from subgroup analyses.

AIMS: To quantify the magnitude of the association between alcohol and oral and pharyngeal cancer (OPC) by sex, smoking habits, type of alcoholic beverage and other factors. METHODS: We combined findings from all case-control and cohort studies published until September 2010 and present in this article the results classified by these factors, using a meta-analytic approach. Summary relative risks (RRs) were obtained using random-effects models; heterogeneity was assessed using the χ(2) test. RESULTS: The association between alcohol and OPC risk was similar in men and women, with similar dose-response relationships. No notable differences were found with respect to geographic area and other factors, both for drinking overall and heavy (≥4 drinks/day) drinking. Among never/non-current smokers, the pooled RRs were 1.32 (95% confidence interval, CI, 1.05-1.67) for drinking, and 2.54 (95% CI, 1.80-3.58) for heavy drinking. The corresponding RRs in smokers were 2.92 (95% CI, 2.31-3.70) and 6.32 (95% CI, 5.05-7.90). The pooled RRs for any drinking irrespective of smoking were 2.12 (95% CI, 1.37-3.29) for wine-, 2.43 (95% CI, 1.92-3.07) for beer- and 2.30 (95% CI, 1.78-2.98) for spirits-only drinking. The corresponding RRs for heavy drinking were 4.92 (95% CI, 2.80-8.65), 4.20 (95% CI, 1.43-12.38) and 5.20 (95% CI, 2.77-9.78). CONCLUSION: The alcohol-related RRs are similar with respect to sex, geographic area and type of alcoholic beverage. The association between alcohol and OPC is stronger in smokers than in non-smokers.

Concentrations of IGF-I and IGFBP-3 and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Insulin-like growth factors (IGFs) and their binding proteins (BPs) regulate cell differentiation, proliferation and apoptosis, and may have a role in the aetiology of various cancers. Information on their role in pancreatic cancer is limited and was examined here in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. METHODS: Serum concentrations of IGF-I and IGFBP-3 were measured using enzyme-linked immunosorbent assays in 422 cases and 422 controls matched on age, sex, study centre, recruitment date, and time since last meal. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounding variables. RESULTS: Neither circulating levels of IGF-I (OR=1.21, 95% CI 0.75-1.93 for top vs bottom quartile, P-trend 0.301), IGFBP-3 (OR=1.00, 95% CI 0.66-1.51, P-trend 0.79), nor the molar IGF-I/IGFBP-3 ratio, an indicator of free IGF-I level (OR=1.22, 95% CI 0.75-1.97, P-trend 0.27), were statistically significantly associated with the risk of pancreatic cancer. In a cross-classification, however, a high concentration of IGF-I with concurrently low levels of IGFBP-3 was related to an increased risk of pancreatic cancer (OR=1.72, 95% CI 1.05-2.83; P-interaction=0.154). CONCLUSION: On the basis of these results, circulating levels of components of the IGF axis do not appear to be the risk factors for pancreatic cancer. However, on the basis of the results of a subanalysis, it cannot be excluded that a relatively large amount of IGF-1 together with very low levels of IGFBP-3 might still be associated with an increase in pancreatic cancer risk.

Inflammation marker and risk of pancreatic cancer: a nested case-control study within the EPIC cohort.

BACKGROUND: Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce. METHODS: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-α (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models. RESULTS: None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR=1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR=1.97 (95% CI 1.02-3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI. CONCLUSION: Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer.

[Anatomic-topographic peculiarities of sub- and supratentorial petroclival meningiomas].

The data about anatomic-topographic peculiarities of petroclival sub- and supratentorial meningiomas were presented. There were operated on 24 patients, of them 5 have died. Three main topographoanatomic variants were delineated, depending on the tumor primary origin and topographic peculiarities present. The most frequent variant of the tumor localization was a lower one. Depending on the variant of the tumor localization present, the peculiarities of interrelationship between the tumor and nerves, vessels and the brain stem are determined.

Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear. METHODS: We examined the associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327,396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use. RESULTS: Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41-0.75) lower risk compared with users of 1 year or less (P-trend, <0.01). Compared with nulliparous women, parous women had a 29% (HR, 0.71; 95% CI, 0.59-0.87) lower risk, with an 8% reduction in risk for each additional pregnancy. A high age at menopause was associated with a higher risk of ovarian cancer (>52 vs ≤ 45 years: HR, 1.46; 95% CI, 1.06-1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk. CONCLUSION: This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors.

Alcohol drinking and colorectal cancer risk: an overall and dose-response meta-analysis of published studies.

BACKGROUND: The International Agency for Research on Cancer (IARC) concluded that alcohol consumption is related to colorectal cancer (CRC). However, several issues remain unresolved, including quantification of the association for light (≤1 drink/day) and moderate (2-3 drinks/day) alcohol drinking, investigation of the dose-response relationship, and potential heterogeneity of effects by sex, colorectal site, and geographical region. METHODS: Twenty-seven cohort and 34 case-control studies presenting results for at least three categories of alcohol intake were identified from a PubMed search of articles published before May 2010. The summary relative risks (RRs) were estimated by the random effects model. Second-order fractional polynomials and random effects meta-regression models were used for modeling the dose-risk relation. RESULTS: The RRs were 1.21 [95% confidence interval (CI) 1.13-1.28] for moderate and 1.52 (95% CI 1.27-1.81) for heavy (≥4 drinks/day) alcohol drinking. The RR for moderate drinkers, compared with non-/occasional drinkers, was stronger for men (RR = 1.24, 95% CI 1.13-1.37) than for women (RR = 1.08, 95% CI 1.03-1.13; P(heterogeneity) = 0.02). For heavy drinkers, the association was stronger in Asian studies (RR = 1.81, 95% CI 1.33-2.46; P(heterogeneity) = 0.04). The dose-risk analysis estimated RRs of 1.07 (95% CI 1.04-1.10), 1.38 (95% CI 1.28-1.50), and 1.82 (95% CI 1.41-2.35) for 10, 50, and 100 g/day of alcohol, respectively. CONCLUSIONS: This meta-analysis provides strong evidence for an association between alcohol drinking of >1 drink/day and colorectal cancer risk.

Effect of plant-based diets on obesity-related inflammatory profiles: a systematic review and meta-analysis of intervention trials.

Plant-based dietary interventions have been proposed to reduce obesity induced chronic low-grade inflammation and hence prevent chronic disease risk; however, human evidence remains unclear. This systematic review and meta-analysis of intervention trials aimed to assess the effect of plant-based diets on obesity-related inflammatory biomarker profiles. Medline, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles published until January 2016 and mean differences in biomarkers of inflammatory status were assessed for: C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-ɑ), soluble intercellular adhesion molecule 1 (sICAM), leptin, adiponectin and resistin. Of initially identified 2,583 publications, 29 met the meta-analysis inclusion criteria [a total of 2,689 participants]. Consumption of plant-based diets was associated with a reduction in the mean concentrations of the following biomarkers: CRP [effect size, -0.55 mg/l, 95% confidence intervals (CI): -0.78; -0.32, I2 = 94.4%], IL-6 [effect size, -0.25 ng/l, 95% CI: -0.56; 0.06, I2 = 74%], and, to some degree, sICAM (-25.07 ng/ml [95% CI: -52.32; 2.17, I2 = 93.2%]). No substantial effects were revealed for TNF-ɑ, resistin, adiponectin and leptin. Plant-based diets are associated with an improvement in obesity-related inflammatory profiles and could provide means for therapy and prevention of chronic disease risk.

Body weight gain and risk of colorectal cancer: a systematic review and meta-analysis of observational studies.

While the relationship between body mass index as an indicator of excess body weight and the risk of colorectal cancer (CRC) is well established, the association between body weight gain in adulthood and risk of CRC remains unresolved. We quantified this association in a meta-analysis of 12 observational studies published until November 2014 with a total of 16,151 incident CRC cases. Random effect models were used to obtain summary relative risks (RR) and 95% confidence intervals (95% CIs). Between-study heterogeneity was assessed using I(2) statistics. Overall, the summary RR (95% CI) was 1.22 (1.14-1.30) for high body weight gain (midpoint: 15.2 kg) compared with stable weight (P for heterogeneity = 0.182; I(2) = 21.2%). In a dose-response analysis, each 5 kg weight gain was associated with a 4% (95% CI: 2%-5%) higher risk of CRC. The association persisted after adjustment for body weight at younger age and was present for both men and women, as well as for colon and rectal cancer. Differences by sex were detected for colon cancer (P for interaction = 0.003, with higher risk for men than women), but not for rectal cancer (P for interaction = 0.613). In conclusion, these data underscore the importance of body weight management from early adulthood onwards for the prevention of CRC development.

Scanning tunnelling microscopic investigation of fullerene monolayers.

C(60) fullerene monolayers have been investigated by scanning tunnelling microscopy/spectroscopy. Single C(60) molecules have been resolved and a regular surface lattice structure of fullerene - in - surfactant is observed. Tunnel electron spectroscopic measurements results in typical I(V) curves which are interpreted in terms of the two-junction Coulomb blockade effect.

Mayak workers study cohort. An inter-institutional comparison of causes of death in the cause-of-death register of Ozyorsk in the Russian Federation.

BACKGROUND: The cause-of-death register at the Southern Urals Biophysics Institute (SUBI), Ozyorsk, Russia, was established to document the number and causes of deaths in the Mayak workers cohort, which includes all persons (N = 22,377) employed at Mayak nuclear facility between 1948 and 1982. Most workers were occupationally exposed to high doses of ionizing radiation and have been shown to have increased risks of various chronic diseases including cancer. OBJECTIVES: To investigate the quality of cause of death coding in the SUBI register. METHODS: A random sample of 246 deaths (~1% of the total) was coded independently at the SUBI and the Danish Cancer Society using the International Classification of Diseases 9 (ICD-9). Proportions of matching codes were calculated. RESULTS: Overall, 233 deaths (95%) were identically classified using the ICD-9 main category matching. Excluding mismatches that were considered to be incorrectly coded during validation, the validity of the register increased to 98%. Using the specific ICD-9 first three-digit matching, 182 deaths were identically coded (74%) and the respective validity of the register was 85%. There were also some non-resolvable discrepancies demonstrating limitations of assigning one code for each death or using language-adapted ICD-9 version. CONCLUSIONS: This validation study was an important quality check of a register used for mortality follow-up in a highly influential epidemiological study on radiation-related health effects. The results of the inter-institutional comparison were generally favourable; however, since the comparison revealed individual mismatches and some systematically differing coding practices, it is essential to repeat it on a regular basis in order to maintain a high quality.

[Differential treatment of focal traumatic brain injury]. / Differentsirovannoe lechenie ochagovogo travmaticheskogo povrezhdeniia golovnogo mozga.

On the basis of observation of 65 patients with focal traumatic injury to the brain (hematoma of mater encephali was noted in 24, intracerebral--in 27, a focus of type III brain contusion--in 24, type IV--in 11, multiple hematomas and foci on contusion-crush--in 21), the criteria for their non-surgical treatment have been substantiated. Choice of a method for the treatment depends on the sizes of a hematoma, focus of contusion-crush, location of an injury, degree of its influence on the brain structures (deformation, shift), value of intracerebral pressure, dynamics of the clinico-roentgenologic symptoms.