Publications

The relationship between intake of selected micronutrients and gastric cancer risk was investigated using data from a case-control study conducted in Italy between 1985 and 1992 on 723 cases of histologically confirmed, incident gastric cancer, and 2024 controls hospitalized for acute, nonneoplastic, nondigestive tract diseases. Relative risks of subsequent quintiles of intake were computed after allowance for sex, age, and other major identified potential confounding factors, including an estimate of total calorie intake. No trend in risk emerged for intake of retinol, vitamin D and vitamin E, whereas a protective pattern was observed for consumption of beta-carotene, ascorbic acid, folate, and nitrates, with risk estimates for the highest intake quintiles of 0.27, 0.40, 0.58, and 0.43, respectively. Significant direct trends in risk were found for methionine, calcium, and nitrites. When the effect of various micronutrients was taken into account, a residual protective effect was observed for beta-carotene and ascorbic acid, and a direct association with methionine remained, whereas the protective effect of folates and nitrates and the direct associations of nitrites were no longer evident. The risk estimates for the upper quintiles of beta-carotene, ascorbic acid, and methionine consumption were respectively 0.38, 0.53, and 2.40, and all the trends in risk were significant and consistent across strata of sex and age. Whether this reflects a specific effect of these micronutrients, rather than problems of collinearity or other limitations of the data, is open for discussion. Nonetheless, these data indicate that selected micronutrients may have an impact in the process of gastric carcinogenesis.

Using data from a case-control study conducted between 1984 and 1992 in the provinces of Milan and Pordenone, northern Italy, on 439 cases of oral and pharyngeal cancers and 2106 hospital controls, we computed the population attributable risk for oropharyngeal cancer in relation to tobacco, alcohol, and a measure of low beta-carotene intake. Two different models were used for estimating relative risks, one assuming that the three factors act multiplicatively on the relative risk and the second estimating separately each combination of alcohol and tobacco and assuming a multiplicative model only for beta-carotene. The estimated attributable risks were similar for the two models considered. For both models and both sexes, the single factor with the highest attributable risk was smoking, which accounted for 81-87% of oral cancers in males and for 42-47% in females. Alcohol explained about 60% of male cases, but only 15% of female ones, and low beta-carotene accounted for 24% of total cases (25% of males, 17% of females). Together the three factors were responsible for 91-94% of oropharyngeal cancers in males, 51-57% in females, and 85-88% in both sexes combined. The present knowledge of major identified risk factors could, in principle, reduce the burden of the disease in Italy from 2400 to about 200 deaths per year for males and from 500 to 230 for females, thus explaining the difference in incidence and mortality between the two sexes.

Carcinoma in situ (CIS) of the breast has increased many-fold in incidence rates and as a proportion of new breast cancers following the introduction of mammographic breast screening. To provide population-based estimates of invasive breast cancer risk following CIS, we linked data on 249 incident primary CIS (median age 53 years) to the Cancer Registry of the Swiss Canton of Vaud (about 600,000 inhabitants) over the period 1977-1994. Women with concurrent invasive cancers of the breast were not included. Standardized incidence ratios (SIR) were determined according to the exact Poisson distribution, with stratification for age and year of diagnosis. A total of 24 cases of breast cancer vs. 3.4 expected [SIR = 7.2, 95% confidence interval (CI): 4.6-10.6], and 7 cases of other neoplasms (except non-melanomatous skin cancer) vs. 6.9 expected (SIR=1.0, 95% CI: 0.4-2.1) were observed. The SIR was 10.4 during the first year, 5.6 between I and 4 years, and 7.7 after > or = 5 years after CIS diagnosis. SIRs were consistent in women below and above age 55 years, but somewhat higher for ductal (SIR=8.6) than lobular (SIR = 4.2) CIS. Six deaths from breast cancer were observed vs. 1.5 expected (standardized mortality ratio=4.0, 95% CI: 1.5-8.7). In 13/19 ductal CIS, but in 2/4 lobular CIS, invasive cancer occurred in the same breast. In most women, CIS and subsequent invasive cancer showed the same morphological (i.e., ductal or lobular) features. The cumulative risk of breast cancer was 16% 10 years after CIS diagnosis, emphasizing the importance of adequate surveillance of women after CIS of the breast.

a'Mario Negri' Institute for Pharmacological Research bInstitute of Medical Statistics and Biostatistics, University of Milan, Milan, Italy Correspondence to Professor Carlo La Vecchia, Istituto di Ricerche Farmacologiche 'Mario Negri', via Eritrea 62, 20157 Milan, Italy Tel: +39 02 3901 4527; e-mail: [email protected]

Mortality from 13 principal cancer sites, plus total cancer mortality at age 65-84 in 22 European countries, the United States, and Japan was analyzed. After earlier increases, total cancer mortality at age 65-84 has been declining between the late 1980s and the late 1990s in the European Union (-5.5% in males, -4.5% in females), in United States males (-2.3%), but not females (+4.4%), and in Japanese females (-5.6%), but not males (+6.3%). Cancer mortality in the elderly rose for both sexes in Eastern Europe between the late 1980s and the late 1990s. Gastric cancer mortality steadily declined in all the areas considered. Lung cancer rates at age 65-84 declined over the last decade by 8.5% in males in the European Union, and by 0.9% in the United States. Rates increased in Eastern Europe, in Japanese males, and in females in all areas. In women, an approximately threefold difference was evident between lung cancer rates of 67-77 per 100,000 in Japan and Europe in the late 1990s, and the rates of 212 per 100,000 in the United States. Likewise, pancreatic cancer mortality rates increased in the elderly of both sexes in the European Union and Japan up to the late 1980s, and in Eastern Europe up to the 1990s, whereas these rates decreased for United States males over more recent calendar periods, thus again reflecting the different spread of the tobacco-related cancer epidemic. After earlier increases in most areas, female breast cancer mortality in elderly women declined over the last decade by 8% in the United States and by 3% in the European Union, whereas it increased in Eastern Europe and Japan. Prostate cancer mortality declined in the European Union and the United States, whereas it rose in Eastern Europe and Japan. Most rates for breast, prostate, and ovarian cancers in the elderly remained comparatively low in Japan. Leukemia mortality in the elderly was stable in most areas, with some evidence of leveling off in the European Union. Mortality from multiple myeloma steadily increased by 10-20% over the last decade in both sexes in all geographic areas considered, and mortality from lymphomas increased, but improved diagnosis and certification may have played a relevant role in these trends.