Federica Turati

Hepatocellular carcinoma epidemiology

Primary liver cancer (namely hepatocellular carcinoma, HCC) is worldwide the fifth most common cancer in men and the seventh one in women, and it represents the third most frequent cause of cancer death. HCC rates are particularly high in eastern/south-eastern Asia and in Africa, intermediate in Southern Europe, and low in most high-income countries. Persistent infections by HBV or HCV are the main recognized risk factors for HCC. Aflatoxin exposure is also an important risk factor for HCC development in Africa and eastern Asia. In high-income countries heavy alcohol drinking, tobacco smoking, overweight, diabetes, familial/genetic factors, and selected dietary aspects, have a relevant role. Updated geographic patterns and time trends in mortality from HCC in Europe, USA, Japan, and Australia are provided in the present review, together with an overview of relevant etiologic factors for HCC and main measures for the prevention of this neoplasm.

Probiotics supplementation during pregnancy or infancy for the prevention of atopic dermatitis: A meta-analysis

Background: The study of probiotics to prevent allergic conditions has yielded conflicting results in children. We undertook a meta-analysis of randomized controlled trials to investigate whether probiotic use during pregnancy and early life decreases the incidence of atopic dermatitis and immunoglobulin E (IgE)-associated atopic dermatitis in infants and young children. Methods: We performed a systematic literature search in Medline, Embase, and Cochrane Library, updated to October 2011. The intervention was diet supplementation with probiotics versus placebo. Primary outcomes were incidence of atopic dermatitis and IgE-associated atopic dermatitis. We calculated summary relative risks (RRs) and corresponding 95% confidence intervals (CIs), using both fixed- and random-effects models. We computed summary estimates across several strata, including study period, type of patient, dose, and duration of intervention, and we assessed the risk of bias within and across trials. Results: We identified 18 publications based on 14 studies. Meta-analysis demonstrated that probiotic use decreased the incidence of atopic dermatitis (RR = 0.79 [95% CI = 0.71−0.88]). Studies were fairly homogeneous (I2 = 24.0%). The corresponding RR of IgE-associated atopic dermatitis was 0.80 (95% CI = 0.66−0.96). No appreciable difference emerged across strata, nor was there evidence of publication bias. Conclusions: This meta-analysis provided evidence in support of a moderate role of probiotics in the prevention of atopic dermatitis and IgE-associated atopic dermatitis in infants. The favorable effect was similar regardless of the time of probiotic use (pregnancy or early life) or the subject(s) receiving probiotics (mother, child, or both).

Risk factors for falls in older people in nursing homes and hospitals. A systematic review and meta-analysis

This is a systematic review and meta-analysis aimed at providing a comprehensive and quantitative review of risk factors for falls in older people in nursing homes and hospitals. Using MEDLINE, we searched for prospective studies investigating risk factors for falls in nursing home residents (NHR) and older hospital inpatients (HI). When there were at least 3 studies investigating a factor in a comparable way in a specific setting, we computed the pooled odds ratio (OR) using random effect models. Twenty-four studies met the inclusion criteria. Eighteen risk factors for NHR and six for HI were considered, including socio-demographic, mobility, sensory, medical factors, and medication use. For NHR, the strongest associations were with history of falls (OR=3.06), walking aid use (OR=2.08) and moderate disability (OR=2.08). For HI, the strongest association was found for history of falls (OR=2.85). No association emerged with age in NHR (OR=1.00), while the OR for a 5years increase in age of HI was 1.04. Female sex was, if anything, associated with a decreased risk. A few other medical conditions and medications were also associated with a moderately increased risk. For some important factors (e.g. balance and muscle weakness), a summary estimate was not computed because the measures used in various studies were not comparable. Falls in older people in nursing homes and hospitals have multifactorial etiology. History of falls, use of walking aids and disability are strong predictors of future falls.

Metabolic syndrome and hepatocellular carcinoma risk.

Background:Hepatocellular carcinoma (HCC) has been associated to diabetes and obesity, but a possible association with the metabolic syndrome (MetS) and its potential interaction with hepatitis is open to discussion.Methods:We analysed data from an Italian case–control study, including 185 HCC cases and 404 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from unconditional logistic regression models.Results:Among the MetS components, diabetes and obesity (i.e, body mass index (BMI)⩾30 kg m−2) were positively associated to HCC risk, with ORs of 4.33 (95% CI, 1.89–9.86) and 1.97 (95% CI, 1.03–3.79), respectively. The ORs for the MetS were 4.06 (95% CI, 1.33–12.38) defining obesity as BMI⩾25, and 1.92 (95% CI, 0.38–9.76) defining it as BMI⩾30. The risk increased with the number of MetS components, up to an almost four-fold excess risk among subjects with ⩾2 MetS factors. Among subjects without chronic infection with hepatitis B and/or C, the OR for those with ⩾2 MetS components was over six-fold elevated. There was no consistent association in subjects with serological evidence of hepatitis B and/or C infection.Conclusion:This study found that the risk of HCC increases with the number of MetS components in subjects not chronically infected with hepatitis viruses.

A meta-analysis of body mass index and esophageal and gastric cardia adenocarcinoma

BACKGROUND The incidence rates of esophageal and gastric cardia adenocarcinoma (EGCA) have increased over recent years in several countries, and overweight/obesity has been suggested to play a major role in these trends. In fact, higher body mass index (BMI) has been positively associated with EGCA in several studies. MATERIAL AND METHODS We conducted a meta-analysis of case-control and cohort studies on the BMI and EGCA updated to March 2011. We estimated overall relative risks (RRs) and 95% confidence intervals (CI) for BMI between 25 and 30 and BMI ≥ 30 kg/m(2), when compared with normo-weight subjects, using random-effects models. RESULTS We identified 22 studies, including almost 8000 EGCA cases. The overall RR was 1.71 (95% CI 1.50-1.96) for BMI between 25 and 30, and was 2.34 (95% CI 1.95-2.81) for BMI ≥ 30 kg/m(2). The continuous RR for an increment of 5 kg/m(2) of BMI was 1.11 (95% CI 1.09-1.14). The association was stronger for esophageal adenocarcinoma (RR for BMI ≥ 30 kg/m(2) = 2.73, 95% CI 2.16-3.46) than for gastric cardia adenocarcinoma (RR for BMI ≥ 30 kg/m(2) = 1.93, 95% CI 1.52-2.45). No substantial differences emerged across strata of sex and geographic areas. CONCLUSION Overweight and obesity are strongly related to EGCA, particularly to espophageal adenocarcinoma.

Fruit and vegetables and cancer risk: a review of southern European studies.

High intakes of fruit and vegetables may reduce the risk of cancer at several sites. Evidence has been derived mainly from case-control studies. We reviewed the relationship between consumption of vegetables and fruit and the risk of several common cancers in a network of Italian and Swiss case-control studies including over 10,000 cases of fourteen different cancers and about 17,000 controls. Data were suggestive of a protective role of vegetable intake on the risk of several common epithelial cancers. OR for the highest compared with the lowest levels of consumption ranged from 0.2 (larynx, oral cavity and pharynx) to 0.9 (prostate). Inverse associations were found for both raw and cooked vegetables, although for upper digestive tract cancers the former were somewhat stronger. Similar inverse associations were found for cruciferous vegetables. Frequent consumption of allium vegetables was also associated with reduced risk of several cancers. Fruit was a favourable correlate of the risk of several cancers, particularly of the upper digestive tract, with associations generally weaker than those reported for vegetables. A reduced risk of cancers of the digestive tract and larynx was found for high consumption of citrus fruit. Suggestive protections against several forms of cancer, mainly digestive tract cancers, were found for high consumption of apples and tomatoes. High intakes of fibres, flavonoids and proanthocyanidins were inversely related to various forms of cancer. In conclusion, data from our series of case-control studies suggested a favourable role of high intakes of fruit and vegetables in the risk of many common cancers, particularly of the digestive tract. This adds evidence to the indication that aspects of the Mediterranean diet may have a favourable impact not only on CVD, but also on several common (epithelial) cancers, particularly of the digestive tract.

Family history of liver cancer and hepatocellular carcinoma.

Familial clustering of hepatocellular carcinoma (HCC) has been frequently reported in eastern Asiatic countries, where hepatitis B infection is common. Little is known about the relationship between family history of liver cancer and HCC in Western populations. We carried out a case‐control study in Italy, involving 229 HCC cases and 431 hospital controls. Data on family history were summarized through a binary indicator (yes/no) and a family history score (FHscore), considering selected family characteristics. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were obtained from unconditional multiple logistic regression models, including terms for age, sex, study center, education, tobacco smoking, alcohol drinking, hepatitis B surface antigen, and/or anti–hepatitis C virus positivity. We also performed a meta‐analysis on family history of liver cancer and liver cancer updated to April 2011 using random‐effects models. After adjustment for chronic infection with hepatitis B/C viruses, family history of liver cancer was associated with HCC risk, when using both the binary indicator (OR, 2.38; 95% CI, 1.01‐5.58) and the FHscore, with increasing ORs for successive score categories. Compared to subjects without family history and no chronic infection with hepatitis B/C viruses, the OR for those exposed to both risk factors was 72.48 (95% CI, 21.92‐239.73). In the meta‐analysis, based on nine case‐control and four cohort studies, for a total of approximately 3,600 liver cancer cases, the pooled relative risk for family history of liver cancer was 2.50 (95% CI, 2.06‐3.03). Conclusion: A family history of liver cancer increases HCC risk, independently of hepatitis. The combination of family history of liver cancer and hepatitis B/C serum markers is associated with an over 70‐fold elevated HCC risk. (HEPATOLOGY 2011)

Global trends and predictions in hepatocellular carcinoma mortality

BACKGROUND & AIMS Trends in hepatocellular carcinoma (HCC) mortality rates have increased over recent decades in most countries. It is also the third cause of cancer death worldwide. The aim of this study is to update global trends in HCC mortality to 2014, and predict trends in rates in the EU, USA and Japan to 2020. METHODS Death certification data for HCC over the 1990-2014 period from the World Health Organization database were analyzed. Sixteen European, five American countries, and six other countries worldwide were included, as well as the EU as a whole. RESULTS In European men, mortality rates were stable during the last decade (3.5/100,000). HCC mortality increased in Northern and Central Europe, and decreased in Southern Europe. In the USA, HCC mortality increased by 35% between 2002 and 2012, reaching 3.1/100,000 men in 2012; it is predicted to remain stable to 2020. Reduced mortality rates were observed in East Asia, although they remained around 10-24/100,000 men. In Japan, HCC mortality is predicted to decrease (5.4/100,000 men in 2020). Trends were favorable in the young, but unfavorable in middle aged, except in East Asia. Mortality rates were 3- to 5-fold lower in women than men in most regions, but trends were similar. CONCLUSIONS Control of hepatitis B (HBV) and hepatitis C virus (HCV) infections has contributed to the decrease in HCC-related mortality in East Asia and Southern Europe. Unfavorable trends in other regions can be attributed to HCV (and HBV) epidemics in the 1960s and 1980s, alcohol consumption, increased overweight/obesity, and diabetes. Better management of cirrhosis, HCC diagnosis and treatment are also influencing the mortality trends worldwide. LAY SUMMARY Mortality rates due to HCC have increased in many countries over recent decades. In this study, we updated worldwide mortality trends for HCC from 1990 to 2014, and predicted trends for some countries to 2020. We observed unfavorable trends in Northern and Central Europe, North and Latin America. East Asia showed an improvement, however mortality rates in this region were 2- to 5-fold higher than in most European countries and the Americas. Steady declines to 2020 are predicted for East Asia but not for Europe and the Americas.

Coffee and Tea Intake and Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Background: Only a few studies have explored the relation between coffee and tea intake and head and neck cancers, with inconsistent results. Methods: We pooled individual-level data from nine case-control studies of head and neck cancers, including 5,139 cases and 9,028 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI), adjusting for potential confounders. Results: Caffeinated coffee intake was inversely related with the risk of cancer of the oral cavity and pharynx: the ORs were 0.96 (95% CI, 0.94–0.98) for an increment of 1 cup per day and 0.61 (95% CI, 0.47–0.80) in drinkers of >4 cups per day versus nondrinkers. This latter estimate was consistent for different anatomic sites (OR, 0.46; 95% CI, 0.30–0.71 for oral cavity; OR, 0.58; 95% CI, 0.41–0.82 for oropharynx/hypopharynx; and OR, 0.61; 95% CI, 0.37–1.01 for oral cavity/pharynx not otherwise specified) and across strata of selected covariates. No association of caffeinated coffee drinking was found with laryngeal cancer (OR, 0.96; 95% CI, 0.64–1.45 in drinkers of >4 cups per day versus nondrinkers). Data on decaffeinated coffee were too sparse for detailed analysis, but indicated no increased risk. Tea intake was not associated with head and neck cancer risk (OR, 0.99; 95% CI, 0.89–1.11 for drinkers versus nondrinkers). Conclusions: This pooled analysis of case-control studies supports the hypothesis of an inverse association between caffeinated coffee drinking and risk of cancer of the oral cavity and pharynx. Impact: Given widespread use of coffee and the relatively high incidence and low survival of head and neck cancers, the observed inverse association may have appreciable public health relevance. Cancer Epidemiol Biomarkers Prev; 19(7); 1723–36. ©2010 AACR.

Coffee consumption and risk of colorectal cancer: a meta-analysis of case–control studies

A meta-analysis of case–control studies on coffee consumption and colorectal cancer risk was conducted. Twenty-four eligible studies published before May 2010 were identified, including a total of 14,846 cases of colorectal, colon or rectal cancer. Compared to non/occasional drinkers, the odds ratios (OR) for drinkers were 0.83 (95% CI 0.73–0.95) for colorectal, 0.93 (95% CI 0.81–1.07) for colon and 0.98 (95% CI 0.85–1.13) for rectal cancer, with significant heterogeneity among studies; the corresponding ORs for the increment of 1 cup/day were 0.94 (95% CI 0.91–0.98), 0.95 (95% CI 0.92–0.98), and 0.97 (95% CI 0.95–0.99). For the highest coffee drinkers, the ORs were 0.70 (95% CI 0.60–0.81) for colorectal cancer, 0.75 (95% CI 0.64–0.88) for colon cancer and 0.87 (95% CI 0.75–1.00) for rectal cancer, when compared to non/low drinkers. The results of this meta-analysis of case–control studies suggest a moderate favorable effect of coffee consumption on colorectal cancer risk. The reduced risk was consistent across study design (hospital vs. population based), geographic area, and various confounding factors considered. It may reflect a real protection but also partly or largely be due to reverse causation, i.e. decreased coffee consumption among cases following the onset of bowel symptoms.