The aim of this study was to investigate the health effects induced by exposure to the fungicide mancozeb in Italian vineyard workers. Ninety-three Italian subjects entered the study - 48 vine-growers intermittently exposed to mancozeb and 45 healthy controls. The subjects were investigated three times: before the seasonal application of pesticides (T0), 30 days after the beginning of the application period (T30), and 45 days after T0 (T45). At T0 the comparison between agricultural workers and controls showed a higher prevalence of cold or flu symptoms, a statistically significant lower percentage of monocytes, higher absolute count of T lymphocytes, CD4 and natural killer cells, and lower plasma levels of IgA and IgM in workers. Such differences were not confirmed at T30 and T45. In fact at T30 in exposed workers, besides a significant increase of urinary ethylenethiourea, confirming mancozeb exposure, T lymphocytes, CD4 and natural killer cells, IgA and IgM returned to values comparable to those observed in controls. Moreover, no other differences in clinical signs, haematological, and immune parameters, such as the immune functional capability evaluated as a response to hepatitis B vaccination, was observed. Altogether the differences between exposed and controls were not consistently correlated to any clinical impairment and suggest that the seasonal application of mancozeb does not pose a significant health risk to exposed subjects.

Mortality from testicular cancer in (young) men remains exceedingly high in most Latin American countries. Urgent intervention is required to provide treatment (essentially modern integrated platinum-based chemotherapy) for this largely curable neoplasm in young men.

To the Editor: In a case-control study of 163 women with epithelial ovarian cancer and 159 controls from New York City, Harlap et al. 1 found an inverse relation between number of siblings and ovarian cancer, with a 20% risk reduction per additional sibling. They suggested that heritable conditions associated with parents’ reduced fertility may be an indicator of risk. We were able to consider such a hypothesis on the basis of a large case-control study conducted between 1992 and 1999 in six areas of Italy. 2 Briefly, cases were 1031 women with incident, histologically confirmed epithelial ovarian cancer, and controls were 2441 women admitted to hospital for acute, nonneoplastic conditions (26% traumas, 28% nontraumatic orthopedic conditions, 15% acute surgical conditions, and 31% other miscellaneous diseases). Fewer than 4% of cases and controls approached refused the interview. Trained interviewers questioned cases and controls in the hospital, using a structured questionnaire that included information on personal characteristics and habits, education and other socioeconomic factors, general lifestyle habits, diet, hormonal and reproductive history, and personal and family history of selected medical conditions. The subjects were specifically asked how many sisters and brothers they had. 3 We estimated the odds ratios (OR) of ovarian cancer according to the number of siblings, using unconditional multiple logistic regression models that included terms for age, study center, geographic area, education, parity, oral contraceptive use, personal history of infertility, and family history of ovarian and breast cancer in first-degree relatives. Table 1 gives the distribution of cases and controls according to the number of siblings. Compared with women who had no siblings, the ORs were 1.1 for those with one sibling, 1.3 for two siblings, 1.1 for three siblings, and 1.0 for four or more siblings. The OR for each additional sibling was 0.98 (95% confidence interval [CI] = 0.94–1.01), and corresponding values for each sister and brother were 0.97 (0.92–1.02) and 0.98 (0.92–1.04), respectively.TABLE 1: Distribution of 1031 Ovarian Cancer Cases and 2411 Controls According to Number of Siblings and Corresponding Odds Ratios, Italy 1992–1999Our study, which included an unusually large number of ovarian cancer cases, did not support the hypothesis that number of siblings, as a measure of the fertility of subjects’ parents, affects ovarian cancer risk. These findings are unlikely to be attributable to bias because the response rate was virtually complete, information bias on the number of siblings is unlikely, and allowance was made in the analysis for major identified potential confounding factors. Furthermore, our results concerning menstrual and reproductive factors are consistent with current knowledge of the issue 4; the risk of ovarian cancer was, in fact, inversely related to parity, late age at menarche, early menopause, and longer oral contraceptive use. 2 Cristina Bosetti Eva Negri Silvia Franceschi Renato Talamini Carlo La Vecchia

The relation between lifelong physical activity at work and during leisure-time and the risk of renal cell cancer (RCC) was analyzed in a case-control study conducted in Italy between 1992 and 2004. Cases were 767 subjects with incident, histologically confirmed RCC, and controls were 1,534 patients hospitalized for acute nonneoplastic conditions. Odds ratios (OR) and 95% confidence intervals (CI) for RCC were computed by multiple logistic regression models, conditioned on study center, sex and age, and adjusted for main covariates. Compared to the lowest level of occupational physical activity, the multivariate OR of RCC for the highest level were 0.65 (95% CI 0.49-0.87) at age 12 years, 0.67 (95% CI 0.53-0.84) at age 15-19, 0.74 (95% CI 0.59-0.93) at age 30-39 and 0.71 (95% CI 0.55-0.92) at age 50-59 years, with significant inverse trends in risk. The inverse association was consistent in strata of sex, age at diagnosis, body mass index, smoking habit and alcohol drinking. No significant association was found for leisure-time physical activity. The inverse association between occupational physical activity and RCC risk, if real, may be related to the effects of insulin-like growth factors, or lipid peroxidation and about 9% of cases of RCC in Italy could be avoided by increasing physical activity. However the inverse association might involve confounding by indirect mechanisms, such as body composition or other social class correlates.

We analysed data from a cohort of 1966 subjects (889 men and 1,077 women) employed by an Italian asbestos (mainly textile) company in the period 1946-1984, who were followed-up to 2004. A total of 62,025 person-years of observation were recorded. We computed standardised mortality ratios (SMR) for all causes and selected cancer sites using national death rates for each 5-year calendar period and age group. There were 68 deaths from mesothelioma (25 men and 43 women, 39 pleural and 29 peritoneal) vs 1.6 expected (SMR=4,159), and 109 from lung cancer vs 35.1 expected (SMR=310). The SMRs of pleural/peritoneal cancer were 6661 for subjects exposed only before 30 years of age, 8,019 for those first exposed before 30 and still employed at 30-39 years of age and 5,786 for those first exposed before 30 and still employed at 40 or more years of age. The corresponding SMRs for lung cancer were 227, 446 and 562. The SMR of mesothelioma was strongly related to time since first exposure. The SMR of lung cancer, but not of mesothelioma, appeared to be related to subsequent exposures.

The issue of diet and breast and ovarian cancers has been considered in terms of foods and nutrients, but rarely in terms of dietary patterns. We examined the associations between dietary patterns and breast and ovarian cancers in 2 Italian multicentric case-control studies. Cases were 2,569 breast cancers and 1,031 ovarian cancers hospitalized in 4 Italian areas between 1991 and 1999. Controls were 3,413 women from the same hospital network. Dietary habits were investigated through a validated food-frequency questionnaire. Dietary patterns were identified on a selected set of nutrients through principal component factor analysis. Odds ratios (OR) and 95% confidence intervals (CI) for both cancers were estimated using unconditional multiple logistic regression models on quartiles of factor scores and continuous factor scores. We identified 4 major dietary patterns named Animal products, Vitamins and fiber, Unsaturated fats and Starch-rich. The animal products pattern and the unsaturated fats pattern were inversely associated with breast cancer (OR = 0.74, 95% CI: 0.61-0.91 and OR = 0.83, 95% CI: 0.68-1.00, respectively, for the highest consumption quartile), whereas the starch-rich pattern was directly associated with it (OR = 1.34, 95% CI: 1.10-1.65). The vitamins and fiber pattern was inversely associated with ovarian cancer (OR = 0.77, 95% CI: 0.61-0.98), whereas the starch-rich pattern was directly associated with it (OR = 1.85, 95% CI: 1.37-2.48). In conclusion, the starch-rich pattern is potentially an unfavorable indicator of risk for both breast and ovarian cancers, while the animal products and the vitamins and fiber patterns may be associated with a reduced risk of breast and ovarian cancers, respectively.

The purpose of our study was to investigate the relation in between physical activity in different periods of life at work and in leisure-time and prostate cancer risk. We conducted a case-control study on prostate cancer in Italy between 1991 and 2002, which included 1,294 incident cases of histologically confirmed prostate cancer below 75 years of age and 1,451 controls, who were admitted to hospital for acute nonneoplastic conditions. Odds ratios (OR) of prostate cancer according to physical activity in different periods of life were obtained by unconditional multiple logistic regression models, including terms for age, study centre, education, social class, body mass index, energy intake, family history and other selected covariates. Compared to the lowest level of occupational physical activity, the multivariate ORs for prostate cancer for the highest level were 0.94 (95% confidence interval, CI, 0.75-1.17) at age 15-19, 0.78 (95% CI, 0.63-0.97) at age 30-39 and 0.75 (95% CI, 0.61-0.93) at age 50-59. A significant inverse trend in risk was found for activity at work at ages 30-39 and 50-59. The inverse associations were consistent in strata of age at diagnosis, body mass index, education and social class. No significant association was found for leisure-time physical activity. The inverse association between occupational physical activity and prostate cancer risk may reflect favorable hormonal correlates of physical activity, but residual confounding by socioeconomic covariates cannot be excluded.

Drs. Patil and Mallath suggest that the variability of caffeine metabolism may partly or largely explain the inverse relation between coffee and hepatocellular carcinoma observed in several studies and quantified in our meta-analysis.1 Apart from genetic variability, we also noted in our discussion that a broad spectrum of digestive tract and liver disorders may lead to changes in caffeine metabolism and hence to a reduction in coffee consumption. Thus, such a variability in metabolism may be both genetic and disease-induced. This is the major difficulty in the interpretation of these findings, as already discussed in our paper. Francesca Bravi*, Cristina Bosetti*, Carlo La Vecchia* , * Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy, Istituto di Statistica Medica e Biometria, Università degli Studi di Milano, Milan, Italy.

This short report provides data and statistics of cancer mortality in Italy in 1998, updating previous work on the issue. The material and methods of this report are similar to those previously described. Briefly, cancer death certification numbers by cause and estimates of the resident population in 1998, stratified by sex and quinquennia of age, were abstracted from data provided by the Istituto Nazionale di Statistica (ISTAT). All cancers or groups of cancers, classified according to the standard International Classification of Diseases (ICD), Ninth Revision, were grouped in 31 categories, besides total cancer mortality and other and unspecified sites. We grouped together all intestinal sites, melanomas and non-melanomatous skin neoplasms, all uterine neoplasms (cervix and corpus), all neoplasms of the brain and nerves (benign and malignant), all leukemias, and all non-Hodgkin's lymphomas. Eight tables were produced, including the following statistics: 1) number of deaths, crude and age-standardized death certification rates, and percentages of all cancer deaths for population at all ages and truncated 35-64 years (Table 1 for males and Table 2 for females). Two different standards were used: i) the 1971 Italian census population, corrected for census undercount and subdivided into 16 quinquennia of age from 0-4 to 75-79, plus 80 and over, and ii) the world standard population, for purposes of comparison with other countries; 2) age-specific death certification rates for each sex and quinquennium of age from 0-4 to 75-79, plus 80 and over (Table 3 for males and Table 4 for females); 3) total number of registered deaths for each cancer or group of cancers, sex and age group (Table 5 for males and Table 6 for females); 4) percentage of all cancer deaths for each sex and age group (Table 7 for males and Table 8 for females). A few comments are included, mainly in order to assist reading and interpretation of data for major cancer sites, and to recall underlying long-term tendencies. Any inference should in any case be based on age-standardized rates, and, essentially, on detailed inspection of age-specific rates.

The present findings suggest a limited effect of the IGF system on endometrial cancer risk. Increasing IGFBP-1 levels seem to be associated with endometrial cancer risk in older women and in women with a higher body mass index.