Carlo La Vecchia

Epidemiology and Risk Factors of Urothelial Bladder Cancer

CONTEXTnUrothelial bladder cancer (UBC) is a disease of significant morbidity and mortality. It is important to understand the risk factors of this disease.nnnOBJECTIVEnTo describe the incidence, prevalence, and mortality of UBC and to review and interpret the current evidence on and impact of the related risk factors.nnnEVIDENCE ACQUISITIONnA literature search in English was performed using PubMed. Relevant papers on the epidemiology of UBC were selected.nnnEVIDENCE SYNTHESISnUBC is the 7th most common cancer worldwide in men and the 17th most common cancer worldwide in women. Approximately 75% of newly diagnosed UBCs are noninvasive. Each year, approximately 110 500 men and 70 000 women are diagnosed with new cases and 38 200 patients in the European Union and 17 000 US patients die from UBC. Smoking is the most common risk factor and accounts for approximately half of all UBCs. Occupational exposure to aromatic amines and polycyclic aromatic hydrocarbons are other important risk factors. The impact of diet and environmental pollution is less evident. Increasing evidence suggests a significant influence of genetic predisposition on incidence.nnnCONCLUSIONSnUBC is a frequently occurring malignancy with a significant impact on public health and will remain so because of the high prevalence of smoking. The importance of primary prevention must be stressed, and smoking cessation programs need to be encouraged and supported.

Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement

Evidence clearly shows a chemopreventive effect for aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on colorectal cancer and probably other cancer types; however, data on the risk-benefit profile for cancer prevention are insufficient and no definitive recommendations can be made. Aspirin has emerged as the most likely NSAID for use in chemoprevention because of its known cardiovascular benefit and available safety and efficacy data. Other traditional NSAIDs, particularly sulindac, and selective COX-2 inhibitors are now given to patients at high risk of colorectal cancer, although these drugs do not provide cardioprotection. More studies of aspirin and cancer prevention are needed to define the lowest effective dose, the age at which to initiate therapy, the optimum treatment duration, and the subpopulations for which the benefits of chemoprevention outweigh the risks of adverse side-effects. Although it might be possible to answer some of these questions with longer follow-up of existing clinical trials, randomised controlled trials with new study designs will be needed. Future projects should investigate the effects of aspirin treatment on multiple organ systems. Cancers of interest are colorectal, breast, prostate, lung, stomach, and oesophageal. The main side-effect of aspirin is peptic ulcers; therefore coadministration of aspirin with a proton-pump inhibitor is an attractive option and is under investigation in the AspECT trial.

Diet and prostatic cancer: a case-control study in northern Italy.

The relationship between intake of various indicator foods and beverages and risk of prostatic cancer was assessed in 271 cases of prostatic cancer and 685 hospital controls recruited in two areas of northern Italy, the province of Pordenone and the greater Milan area. Increased risks were found for more frequent intake of meat [odds ratio (OR) in the highest vs. lowest consumption tertile = 1.4, 95% confidence interval (CI) 1.0-2.0], milk (OR = 1.6, 95% CI 1.1-2.4), fresh fruit (OR = 1.4, 95% CI 1.0-2.1), and vegetables (OR = 1.4, 95% CI 0.9-2.2). After allowance for the reciprocal confounding effect of various dietary habits, only frequent intake of milk seemed to be a significant independent indicator of prostatic cancer risk. There was also a clue that the unfavorable influence of frequent intake of a few food items (i.e. meat, fish, liver, ham and salami, milk and butter, and retinol) may be greater or restricted to older individuals (i.e., > or = 70 yrs of age). In conclusion, the present study confirms the presence of a moderate adverse effect of high intake of foods of animal origin, chiefly milk, while it suggests that a diet rich in fresh fruit and vegetables does not convey a protection.

The changing pattern of kidney cancer incidence and mortality in Europe.

To update trends in kidney cancer mortality in 32 European countries and the European Union (EU) as a whole, as mortality from kidney cancer has increased throughout Europe until the late 1980s or early 1990s, and has tended to stabilise or decline thereafter.

Nutrition and diet in the etiology of endometrial cancer

The risk of endometrial cancer in relation to nutrition and frequency of consumption of a few selected dietary items was evaluated in a case‐control study of 206 patients with endometrial cancer and 206 control subjects with acute conditions unrelated to any of the established or potential risk factors for endometrial cancer. Obesity was strongly and positively associated with the risk of endometrial cancer, and several conditions related to body weight, such as early menarche, diabetes mellitus, or hypertension were more common in cases. The risk of endometrial cancer was elevated in subjects reporting (on a subjective basis) greater fat (butter, margarine, and oil) intake (relative risk estimate for the higher compared to the lower scores equals 5.65, with 95% confidence interval of 2.76–11.55). Cases reported less frequent intake of green vegetables, fruit, and whole‐grain foods: thus, the risk of endometrial cancer appeared inversely related to indices of beta‐carotene and fiber intake. Furthermore, cases consumed milk, liver and fish less frequently than controls. No significant difference was noted between cases and controls in the frequency of intake of carrots, meat, eggs, ham, and cheese. Alcohol consumption was somewhat larger among the cases, but this trend in risk was not significant. Dietary information collected in this study probably is too limited and inconsistent to permit analysis of biologic correlates of these findings or discussion of their potential implications in terms of prevention on a public health scale. Nonetheless, the mere existence of differences in reported diet between endometrial cancer cases and controls is of interest, and may warrant further, more detailed investigation.

Medical history, diet and pancreatic cancer.

The relation between various aspects of medical history, selected indicator foods and the risk of pancreatic cancer was analyzed in a hospital-based case-control study conducted in Northern Italy on 247 patients with cancer of the pancreas, and 1,089 controls in hospitals for acute, nonneoplastic or digestive conditions. There was a significant association with history of pancreatitis (relative risk, RR 3.2, 95% confidence interval = 1.3-7.9), which was however reduced when the condition was first diagnosed at least 5 years previously. The point estimates were slightly, but not significantly, above unity for diabetes (RR = 1.5), gastrectomy (RR = 1.1) and cholelithiasis (RR = 1.3), and no association was found with liver disease or drug allergy. In relation to diet, there was some tendency for the risk to decrease with more frequent fruit consumption, but the results were largely inconsistent in relation to various indicators of meat, animal protein or fat intake. Although no important associations were found in this study with various aspects of medical history or diet indicators and pancreatic cancer risk, on account of the size of the dataset and the statistical power, this study contributes usefully to the debate on a common cancer whose causes are still largely undefined.

Dietary factors in the risk of bladder cancer

The relationship between selected dietary factors and the risk of bladder cancer was investigated in a case-control study conducted in northern Italy. The study included 163 cases and 181 controls who were hospitalized for acute, nonneoplastic or urinary tract diseases. The frequency of consumption of green vegetables and carrots was lower in the cases; thus, the estimated relative risks for the upper vs. the lower tertiles were 0.6 for green vegetables and 0.5 for carrots. Significant inverse trends in risk emerged with estimated carotenoid (as well as retinoid) intake. The apparent protection conveyed by vitamin A was stronger in current smokers. The risk of bladder cancer was not related to scores of fat and measures of alcohol consumption; the risk was elevated in coffee drinkers (although there was no tendency to rise with higher consumption), but it was reduced in tea drinkers. These findings were not explainable in terms of selection, information, or confounding bias. Thus, although available information is too uncertain for any precise definition of specific (micro)nutrients related to bladder cancer risk, the confirmation that several aspects of a less-affluent diet adversely affect the risk is still of interest in terms of a better understanding of bladder carcinogenesis.

Sexual factors, venereal diseases, and the risk of intraepithelial and invasive cervical neoplasia.

The relation between major indicators of sexual habits (age at first intercourse and total number of sexual partners), history of selected venereal diseases, and cervical neoplasia was investigated using data from a case‐control study of 206 cases of cervical intraepithelial neoplasia compared with 206 age‐matched outpatient controls, and of 327 cases of invasive cancer compared with 327 control subjects in hospital for acute conditions unrelated to any of the established or suspected risk factors for cervical cancer. The relative risks increased with decreasing age at first intercourse and increasing number of sexual partners both for intraepithelial and for invasive cancers. The effects of these two variables were independent, since they were only marginally affected by reciprocal adjustment, or by allowance for several other identified potential distorting factors. The negative association with age at first intercourse was particularly strong in the case of invasive cancers, with risk estimates over five‐fold elevated for women reporting their first intercourse before age 18 compared with those aged over 22 years. This relation might be discussed in terms of multistage models of carcinogenesis, which predict that the incidence of epithelial carcinomas is a function of duration of exposure. In fact, when age was allowed for, the relative risks of cervical neoplasia were positively and strongly related with the total duration of the interval between age at diagnosis/interview and age at first intercourse. Clinical histories of several sexually transmitted diseases were positively associated with the risk of intraepithelial neoplasia. In particular, genital warts were reported by nine cases but no control subject. No such association, however, emerged for invasive carcinomas. Thus, the current findings confirm that, although intraepithelial neoplasia and invasive cervical cancer appear to share several important epidemiological features, the specific (infectious) agents implicated in dysplastic lesions probably differ to some extent from those causing invasive cancer.

Alcohol consumption and cancer risk

This review focuses on selected aspects of the relation between alcohol consumption and cancer risk. Heavy alcohol consumption (i.e., ≥4 drinks/day) is significantly associated with an increased risk of about 5-fold for oral and pharyngeal cancer and esophageal squamous cell carcinoma, 2.5-fold for laryngeal cancer, 50% for colorectal and breast cancers, and 30% for pancreatic cancer. These estimates are based on a large number of epidemiological studies and are generally consistent across strata of several covariates. The evidence suggests that at low doses of alcohol consumption (i.e., ≤1 drink/day) the risk is also increased by about 20% for oral and pharyngeal cancer and 30% for esophageal squamous cell carcinoma. Thus, for these sites there is little evidence of a threshold effect. While consumption of fewer than 3 alcoholic drinks/wk is not associated with an increased risk of breast cancer, an intake of 3 to 6 drinks/wk might already yield a (small) increase in risk. On the other hand, intakes up to 1 drink/day are not associated to the risk of laryngeal, colorectal, and pancreatic cancer. The positive association between alcohol consumption and the risk of head and neck cancers is independent from tobacco exposure.

Effect of omega-3 fatty acids supplementation on depressive symptoms and on health-related quality of life in the treatment of elderly women with depression: a double-blind, placebo-controlled, randomized clinical trial.

Objective: In elderly individuals, depression is one of the most frequently missed diagnoses with negative effects on quality of life. The authors investigated whether a supplement containing long-chain omega-3 polyunsaturated fatty acids (n-3 LCPUFA) improves depressive symptoms and health-related quality of life (HRQoL) in depressed elderly patients. Design: Eight-week, randomized, double-blind, placebo-controlled trial. Setting: Nursing home in Pavia, Italy. Participants: Forty-six depressed women, aged 66–95 years. Intervention: Twenty-two depressed women were included in the intervention group (n-3 group, which received 2.5 g/d of n-3 LCPUFA, with 1.67 g of eicosapentaenoic acid [EPA] and 0.83 g of docosahesaenoic acid [DHA]), and 24 patients were included in the placebo group. The primary endpoint was the improvement of depressive symptoms, as evaluated by the Geriatric Depression Scale (GDS). Secondary endpoints were the evaluation of HRQoL, by using the Short-Form 36-Item Health Survey (SF-36), and modifications of erythrocyte membrane phospholipids fatty acid profile. All variables were assessed before and after the treatment period of 8 weeks. Results: The mean GDS at 8 weeks was significantly lower compared with the n-3 group. The SF-36 physical and mental components were significantly increased in the intervention group. Compliance was good, as confirmed by erythrocyte membrane phospholipid FA concentrations, with a significant increase of EPA and DHA in the intervention group. Conclusion: Supplementation with n-3 LCPUFA is efficacious in the amelioration of depressive symptoms and quality of life in the treatment of depressed elderly female patients.