The main adverse effects of tamoxifen, aspirin, oral contraceptives (OCs) and retinoids used as chemopreventive agents in humans are reviewed and quantified here. With regard to tamoxifen, there are suggestions of some excess risk of liver, and perhaps gastrointestinal, cancers. The public health impact of such associations, if any, is still unclear. Tamoxifen use is associated with endometrial and myometrial hyperplasia. Data from five studies based on 174 cases indicate that the overall relative risk (RR) of endometrial cancer in ever tamoxifen users is 1.73 (95% confidence interval = 1.1-2.6). However, there is a significant difference between the results of American and European studies, so the relationship between tamoxifen and endometrial cancer remains open to debate. The major side-effect of aspirin is gastrointestinal lesions; the risk of these is increased two- to tenfold, depending on the dose. Aspirin is also associated with an increased risk of haemorrhagic stroke, although its protection against other types of stroke and against myocardial infarction leads to a favourable pattern of risk for all cardiovascular conditions. Short-term side-effects of OCs include vascular diseases and a moderately increased risk of breast cancer. The RR of cervical cancer and hepatocellular carcinoma are also increased in OC users, although the public health impact of such associations is small. Toxicity associated with retinoid treatment is rarely serious as most effects observed are reversible on stopping use. Side-effects include changes in the skin and mucous membranes (dry skin, hair loss, dry nose, conjunctivitis), musculoskeletal symptoms, ophthalmological effects, changes in transaminase activity, changes in clinical chemistry markers (increase in serum triglycerides and decrease in high-density lipoproteins) and, rarely, central nervous system effects. A serious toxicological aspect of retinoid treatment is teratogenesis; its use should therefore be avoided in women with childbearing potential, and, in cases of use, conception should be delayed for a long time after stopping treatment. Thus, when considering side-effects of chemoprevention, the major issues of concern are the rare long-term effects (chiefly neoplasms), and the need for more precise overall risk-and cost-benefit assessment, particularly for healthy people.

A unified analysis of the combined effects of alcohol and smoking in cancers of the upper aerodigestive tract was conducted using polychotomous logistic regression to determine if, at the same level of exposure, risk varies significantly across pathological sites. Data from a case-control study in northern Italy include males with tumors of the oral cavity/pharynx, larynx, and esophagus and males admitted to the hospital for acute illnesses not related to alcohol and smoking. The combined alcohol and smoking risks for oral cavity/pharynx cancer in these data were significantly greater than those for either laryngeal or esophageal cancer, but esophageal cancer and laryngeal cancer could not be distinguished based on risk. The differences may lie in the presence of unspecified factors in the oral cavity and pharynx, but not in the other upper aerodigestive tract sites, which potentiate the effects of alcohol and smoking in the oral cavity/pharynx.

Trends in overweight and obesity among Italian adults, 1983 through 1994. R Pagano, C La Vecchia, A Decarli, E Negri, and S Franceschi Deborah A. Galuska, Mary Serdula, Elsie Pamuk, Paul Z. Siegel, and Tim Byers CopyRight https://doi.org/10.2105/AJPH.87.11.1869 Published Online: October 07, 2011

Alcohol consumption has been linked to an increased risk for various types of cancer. A combined analysis of more than 200 studies assessing the link between alcohol and various types of cancer (i.e., a meta-analysis) sought to investigate this association in more detail. This meta-analysis found that alcohol most strongly increased the risks for cancers of the oral cavity, pharynx, esophagus, and larynx. Statistically significant increases in risk also existed for cancers of the stomach, colon, rectum, liver, female breast, and ovaries. Several mechanisms have been postulated through which alcohol may contribute to an increased risk of cancer. Concurrent tobacco use, which is common among drinkers, enhances alcohol's effects on the risk for cancers of the upper digestive and respiratory tract. The analysis did not identify a threshold level of alcohol consumption below which no increased risk for cancer was evident.

Vecchia, C La1,2; Anelli, M3; Zuccato, E1; Fanelli, R1; Fioretti, F1; Sermeus, G4; Valdicelli, L4; Milazzo, N3 Author Information

The relation between 17 micronutrients and breast-cancer risk was analyzed in a case-control study conducted between 1993 and 1999 in the Swiss Canton of Vaud. Cases were 289 women with incident, histologically confirmed breast cancer, and controls were 442 women admitted to the same hospital for a wide spectrum of acute non-neoplastic conditions unrelated to long-term modifications of diet. Dietary habits were investigated using a validated food-frequency questionnaire. Odds ratios (ORs) were obtained after allowance for age, education, parity, menopausal status, body mass index, total energy intake and alcohol drinking. For several micronutrients, the ORs tended to decline with increasing tertile of intake, with significant inverse trends in risk for potassium (OR for the highest tertile = 0.21), total carotenoids (OR = 0.42), lycopene (OR = 0.43), folic acid (OR = 0.45), vitamin C (OR = 0.19), vitamin E (OR = 0.37) and vitamin B6 (OR = 0.54). In a model including a continuous term for the 7 micronutrients significantly related to breast cancer, the only persisting significant inverse relations were for vitamin C (OR = 0.23) and lycopene (OR = 0.64). © 2001 Wiley-Liss, Inc.

The risk of breast cancer is lower in women who undergo bilateral oophorectomy before menopause, and the protection increases with time from surgery.

Trends in death certification rates from pancreatic cancer over the period 1955-1989 were analyzed for 25 European countries (excluding the former Soviet Union and a few smaller countries). In 1985-1989, rates for males ranged between 5.3/100,000 (age-standardized world population) in Spain and 10.3/100,000 in Hungary and Czechoslovakia. Other high-mortality areas were located in Northern Europe (Finland, Iceland, Ireland, Denmark) and Central Europe (Austria, Poland, Germany), whilst mortality was lower in Southern Europe (Portugal, Greece). Between 1955 and 1989, mortality rates increased in all the countries considered, the change ranging between 6% in Scotland and 279% in Spain; the rises were higher in the Mediterranean and Eastern European countries than in Northern Europe. Among females, Nordic countries such as Iceland, Sweden and Denmark had the highest mortality rates in 1985-1989 (over 6/100,000) and, as for males, Southern Europe (Spain, Portugal, Greece) appeared as a low-mortality area (around 3/100,000). During the 1955-1989 period, upward trends were observed in all the countries studied, with the highest increase in Greece, Italy, Bulgaria, Poland and Spain. A negative correlation was observed between the percent change in mortality rates between 1955-1959 and 1985-1989 and the rate in 1955-1959 among both males (r = -0.95, p < 0.001) and females (r = -0.81, p < 0.001). Thus, a systematic levelling of rates was observed in most countries, with the exception of the UK and some Nordic countries, whose rates were already high in the late 1950s. Tobacco smoking and dietary factors could account for some of the generalized upward trends. Improved diagnostic and death certification of the disease might also partially explain the observed figures.

The relationship between alcohol drinking and gastric cancer risk was analyzed using data from a case-control study conducted in Northern Italy between 1985 and 1993 on 746 cases of histologically confirmed incident stomach cancer and 2,053 controls in hospital for acute nonneoplastic nondigestive tract diseases. Wine was the most frequently consumed alcoholic beverage, accounting for approximately 90% of all alcohol consumption. Compared with those who never drank wine, the odds ratios (OR) were 1.1 [95% confidence interval (CI) 0.9-1.3] for fewer than four drinks per day, 1.3 (95% CI 1.0-1.7) for four to fewer than six drinks per day, 1.6 (95% CI 1.1-2.4) for six to fewer than eight drinks per day, and 1.4 (95% CI 1.0-2.0) for eight or more drinks per day. No association was observed with beer or spirits. For total alcohol consumption, 25% of cases and 30% of controls never drank alcohol, and the multivariate OR for those who drank versus those who did not drink was 1.1 (95% CI 0.9-1.4). After allowance for smoking, education, family history of stomach cancer, selected micronutrient intake, and nonalcohol calorie intake, the ORs were 1.1 (95% CI 0.9-1.4) for fewer than six drinks per day, 1.0 (95% CI 0.4-1.4) for six to fewer than eight drinks per day, and 1.3 (95% CI 0.9-1.9) for eight or more drinks per day, and the trend in risk was not significant. No interaction was observed between alcohol drinking and sex, family history, and smoking, but the association with alcohol drinking was appreciably stronger in the elderly and in less-educated individuals. Thus this large data set was able to exclude a strong and consistent association between alcohol (mainly wine) drinking and stomach cancer risk. A nonsignificant association was observed in those who drank very heavily, but the absence of a dose-risk relationship suggests that even such a moderate association may reflect inadequate allowance for covariates or the presence of other risk factors (possibly related to diet and social class) among the heaviest drinkers.