A. Giacosa

Risk factors for Barrett's esophagus: A case-control study

Barretts esophagus (BE) is an acquired disorder due to chronic gastroesophageal reflux. Environmental factors seem to play an important role in the pathogenesis of BE, especially in Western society. A multicenter case‐control study was carried out between February 1995 and April 1999 in 8 Italian Departments of Gastroenterology gathered in a study group (GOSPE), in order to analyze the influence of some individual characteristics and life‐style habits on the occurrence of BE. Three groups of patients were studied: 149 patients with BE, 143 patients with esophagitis (E) and 308 hospital controls (C) with acute, non‐neoplastic, non‐gastroenterological conditions. The diagnosis of BE was based on endoscopy and histology. E was defined by the Savary classification (grade I–III). Data collection was performed by using a questionnaire that focused on smoking, coffee and alcohol consumption, medical history, drugs history, gastroesophageal reflux disease (GERD) symptoms (heartburn, regurgitation) and socio‐economic status. Multivariate analysis showed that the frequency of weekly GERD symptoms was significantly associated with both BE and E (p<0.0001), such as the presence of hiatal hernia (p≤0.001). Ulcer was significantly associated with BE (p=0.001). Among patients with E, the risk was directly related to spirits consumption (p=0.03). Patients with GERD symptoms that lasted more than 13 years were more likely to have BE than E (p=0.01). In conclusion, results from our study point out that long‐standing GERD symptoms, hiatal hernia and possibly alcohol consumption are risk factors in the development of the BE and E.

Intake of macronutrients and risk of breast cancer

BACKGROUNDnThe association between risk of breast cancer and dietary fat and intakes of other energy sources remains controversial. The Italian population offers special opportunities to assess the influence of high intakes of unsaturated fat and starch and, because the population has low awareness of diet and cancer issues, there is less scope for recall bias. We have assessed the relations of various macronutrient intakes with risk of breast cancer.nnnMETHODSnIn this case-control study, 2569 women with incident breast cancer (median age 55 years) and 2588 control women (median age 56 years) in hospital with acute, non-neoplastic diseases, were interviewed in six different areas of Italy between 1991 and 1994. A validated food-frequency questionnaire was used. It included questions on 78 foods and recipes grouped into six sections, as well as specific questions on individual fat intake pattern.nnnFINDINGSnThe risk of breast cancer decreased with increasing total fat intake (trend p 0.01) whereas the risk increased with increasing intake of available carbohydrates (trend p = 0.002). The odds ratios for women in the highest compared with the lowest quintile of energy-adjusted intake were 0.81 for total fat and 1.30 for available carbohydrates. Starch was the chief contributor to the positive association with available carbohydrates. High intakes of polyunsaturated and unsaturated fatty acids (i.e., polyunsaturated fatty acids plus oleic acid) were associated with a decreased risk of breast cancer (odds ratios for highest vs lowest quintile 0.70 and 0.74, respectively). Conversely, the intakes of saturated fatty acids, protein, and fibre were not significantly associated with breast-cancer risk.nnnINTERPRETATIONnThis case-controls study shows that unsaturated fatty acids protect against breast cancer, possibly because intake of these nutrients is closely correlated with a high intake of raw vegetables. The findings also suggest a possible risk in southern European populations, of reliance on a diet largely based on starch.

Dietary acrylamide and human cancer

Low levels of acrylamide have been found in several foods cooked at high temperatures. While there is sufficient evidence for the carcinogenicity of acrylamide in experimental animals, the few epidemiologic studies conducted to date on occupational and dietary exposure to acrylamide have found no consistent evidence of association with human cancer risk. Using data from an integrated network of Italian and Swiss hospital‐based case‐control studies, we analyzed the relation between dietary acrylamide intake and cancers of the oral cavity and pharynx (749 cases, 1,772 controls), esophagus (395 cases, 1,066 controls), large bowel (1,394 cases of colon, 886 cases of rectal cancer, 4,765 controls), larynx (527 cases, 1,297 controls), breast (2,900 cases, 3,122 controls), ovary (1,031 cases, 2,411 controls) and prostate (1,294 cases, 1,451 controls). All the studies included incident, histologically confirmed cancer cases and controls admitted to the same network of hospitals for acute nonneoplastic conditions. We calculated odds ratios (ORs) using multivariate logistic regression models, adjusted for energy intake and other major covariates of interest. The ORs for the highest versus the lowest quintile of acrylamide intake were 1.12 (95% CI = 0.76–1.66) for cancer of the oral cavity/pharynx, 1.10 (95% CI = 0.65–1.86) for esophageal, 0.97 (95% CI = 0.80–1.18) for colorectal, 1.23 (95% CI = 0.80–1.90) for laryngeal, 1.06 (95% CI = 0.88–1.28) for breast, 0.97 (95% CI = 0.73–1.31) for ovarian and 0.92 (95% CI = 0.69–1.23) for prostate cancer. None of the trend in risk was significant. This uniquely large and comprehensive data set does not show any consistent association between intake of acrylamide and the risk of breast and several other common cancers.

Aspirin and colorectal cancer.

The relationship between aspirin use and colorectal cancer risk was examined by a case-control study in Italy. Regular aspirin use was reported by only 47 (3.5%) cases and 77 (4.1%) control subjects, giving a multivariate odds ratio (OR) of 0.7 (95% CI 0.5-1.0) after allowance for education, physical exercise and selected dietary factors.

Metabolic syndrome and the risk of breast cancer in postmenopausal women

BACKGROUNDnOnly a few small studies investigated the association between postmenopausal breast cancer and metabolic syndrome (MetS) as a single entity.nnnMATERIALS AND METHODSnWe analyzed the data of two Italian and Swiss case-control studies conducted between 1983 and 2007, including 3869 postmenopausal women with incident breast cancer and 4082 postmenopausal controls admitted to the same hospitals as cases for acute conditions. MetS was defined as the presence of at least three components among diabetes, drug-treated hypertension, drug-treated hyperlipidemia, and obesity.nnnRESULTSnThe odds ratios (ORs) of postmenopausal breast cancer were 1.33 [95% confidence interval (CI) 1.09-1.62] for diabetes, 1.19 (95% CI 1.07-1.33) for hypertension, 1.08 (95% CI 0.95-1.22) for hyperlipidemia, 1.26 (95% CI 1.11-1.44) for body mass index ≥30 kg/m(2), and 1.22 (95% CI 1.09-1.36) for waist circumference ≥88 cm. The risk of postmenopausal breast cancer was significantly increased for women with MetS (OR = 1.75, 95% CI 1.37-2.22, for three or more MetS components, P for trend for increasing number of components < 0.0001) and the risk was higher at older age (OR = 3.04, 95% CI 1.75-5.29, at age ≥70 years for three or more MetS components).nnnCONCLUSIONSnThis study supports a direct association between MetS and postmenopausal breast cancer risk.

Sources of macro- and micronutrients in Italian women: results from a food frequency questionnaire for cancer studies.

The knowledge of major sources of macro- and micronutrients is essential in order to interpret differences in the diet-cancer link in various geographical areas and to provide better nutritional guidelines. For this purpose we took advantage of the control group of a case-control study on breast cancer carried out in six Italian areas. The dietary habits of 2,588 cancer-free women aged 20-74 years (median age 56) were elicited between 1991 and 1994 by means of an interviewer-administered food frequency questionnaire (FFQ) that included 78 foods or food groups, in addition to several questions on general dietary pattern (e.g., fat in seasoning). Bread was the first contributor for total energy (12%), protein (8%) and starch (32%) intake, whereas, for saturated fatty acid, the first sources were different types of cheese (28%); for monounsaturated fatty acids the dressing oils of salad and tomatoes (12%); and, for sugars, apples and pears (19%). Raw vegetables and fresh fruit represented the most important source of most vitamins. The first contributors of vitamin C and beta-carotene were citrus fruits (29%) and raw carrots (17%), respectively. Thus, between 40 and 80% of specific macronutrient intake and up to 90% intake of several micronutrients were derived from the first ten foods or food groups. Often, the major contributors to the intake of a specific component were foods with a relatively low content, but eaten in large quantities. This work further highlights the specificity of nutrient sources in southern European populations.

Vitamin D intake and breast cancer risk: a case–control study in Italy

BACKGROUNDnVitamin D has been suggested to play a protective role against several cancers, including breast cancer.nnnPATIENTS AND METHODSnWe used data from a case-control study conducted in Italy from 1991 to 1994 to study the relation between dietary intake of vitamin D and breast cancer risk. Subjects were 2569 women with incident, histologically confirmed breast cancer and 2588 hospital controls. Odds ratios (ORs) and 95% confidence intervals (CIs) according to deciles of vitamin D intake were estimated by multiple logistic regression models.nnnRESULTSnAfter allowance for major risk factors for breast cancer and dietary covariates including calcium and energy intake, there was no association with vitamin D up to the seventh decile. Thereafter, the OR declined, so that the overall trend was statistically significantly inverse. The OR for subjects in the three highest deciles of consumption compared with those in the lowest ones combined was 0.79 (95% CI 0.70-0.90). Intake of vitamin D >3.57 microg or 143 IU appeared to have a protective effect against breast cancer. The inverse association was consistent across strata of menopausal status.nnnCONCLUSIONSnThis study adds to the existing evidence that vitamin D intake in inversely associated with breast cancer risk.

Epidemiology of colorectal polyps.

The prevalence of colorectal adenomatous polyps varies widely from country to country. Among asymptomatic, average-risk patients, adenoma prevalence averages approximately 10% in sigmoidoscopy studies and more than 25% in colonoscopy studies, whereas the prevalence of colorectal cancer among these patients is less than 1%. These data may change in the future due to the advent of new technological approaches and, in particular, chromo- and magnifying endoscopy as well as confocal laser endoscopy. The cumulative incidence of new adenomas within 3 years after normal endoscopy averages about 7% by flexible sigmoidoscopy and 27% by colonoscopy. As far as risk factors for colorectal adenomas are concerned, several data are now available on the potential role of various diet items. Tobacco smoking may be important in the early stages of adenoma formation, but not necessarily in the later stages. Alcohol consumption elevates the risk of adenomatous colorectal polyps and this seems increased by ADH3 polymorphism. Another gene–environment relationship of interest in colorectal tumorigenesis may be based on folate’s effects on K-ras mutations.

ITALIAN STUDY ON COLORECTAL CANCER WITH EMPHASIS ON INFLUENCE OF CEREALS

To elucidate the influence of diet on colorectal carcinogenesis, 1225 subjects with cancer of the colon, 728 with cancer of the rectum and 4154 controls, hospitalized with acute non-neoplastic diseases, were interviewed between 1992 and 1996 in six Italian areas. The validated food frequency questionnaire included 79 questions on food items and recipes which were grouped into 16 food groups. After allowing for nondietary confounding factors and total energy intake, a significant trend towards an increasing risk of colorectal cancer with increasing intake was found for bread and cereal dishes (odds ratio for increase of one daily serving 1.11), cakes and desserts (odds ratio 1.02) and refined sugar (odds ratio 1.11). The intake of fish (odds ratio 0.53), raw and cooked vegetables (odds ratios 0.79 and 0.65, respectively) and fruit (odds ratio 0.93) showed an inverse association with risk. Wholemeal bread was consumed by only 12.5% of cases and 13.9% of controls and, at variance with refined bread, did not show a significant direct association with colorectal cancer risk (odds ratio 0.88). In view of these findings, current hypotheses on the carcinogenic effects of refined starchy foods and refined sugar should be revised to take into account the digestive physiology of carbohydrates and the possible relationship between insulin and colon cancer. The beneficial influence of most vegetables is confirmed, and a possible difference between refined and wholemeal bread is suggested.

Adherence to the European food safety authority's dietary recommendations and colorectal cancer risk

Background/Objective:The European Food Safety Authority (EFSA) recently published dietary guidelines for the intakes of carbohydrates, fiber, fats and water. We evaluated their role on the risk of a specific disease, known to be related to diet.Subjects/Methods:We used data from an Italian case-control study including 1953 colorectal cancer (CRC) cases and 4154 controls. We developed a so-called EFSA index summing up 1 point for adherence to each EFSA guideline. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of CRC and its subsites were derived from unconditional multiple logistic regression models, for both the index and its components.Results:When each EFSA index component was analyzed separately, we found significant increased risks of CRC for non adherence to the guidelines on linoleic (OR=1.20, 95% CI, 1.07–1.36) and alpha-linolenic fatty acids (OR=1.19, 95% CI, 1.06–1.34). When all the guidelines were included in the same model, no significant association emerged. Compared with minimal adherence, the ORs of CRC for subsequent EFSA index scores were 1.03 (95% CI, 0.72–1.47), 1.05 (95% CI, 0.75–1.48), 1.04 (95% CI, 0.81–1.60), 0.99 (95% CI, 0.69–1.43), and 1.04 (95% CI, 0.67–1.61). No significant association emerged for colon and rectal cancer separately, and for males and females.Conclusions:Overall adherence to the EFSA dietary guidelines is not associated to colorectal, colon and rectal cancer risk in our population. Adherence to guidelines on linoleic and alpha-linolenic fatty acids may have a modest beneficial role on CRC risk.