Hormone replacement therapy in menopause has been associated with a moderate increase in ovarian cancer risk. Data on combined estrogen-progestin therapy, based on one randomized trial, two cohort and four case-control studies, do not provide definite evidence of an association between combined hormone replacement therapy and ovarian cancer. These data do not suggest, however, substantial differences between the effect of estrogen only or unspecified hormone replacement therapy and combined hormone replacement therapy on ovarian cancer risk.

The role of dietary carbohydrates in body weight control is still controversial. We investigated the relationship of the dietary glycemic index (GI) and glycemic load (GL) on body mass index (BMI), waist to hip ratio (WHR) and waist circumference (WC) in a cross‐sectional analysis of 4,721 hospital controls from a cancer case‐control series (Italy, 1991–2002). After allowance for confounding variables the odds ratios for the highest versus the lowest quartile of GI and GL were: 0.65 (95% CI: 0.54–0.78) and 0.85 (95% CI: 0.71–1.02) for BMI>=25, 0.67 (95% CI: 0.51–0.89) and 0.69 (95% CI: 0.52–0.92) for BMI>=30, 0.78 (95% CI: 0.64–0.95) and 0.84 (95% CI: 0.69–1.04) for higher WHR, and 0.69 (95% CI: 0.50–0.94) and 0.70 (95% CI: 0.47–1.03) for higher WC. In conclusion GI and GL were not directly related to measures of body weight in this Mediterranean population.

To the Editor: The Iowa Women's Health Study, a prospective study including 37,083 postmenopausal women and 95 cases of multiple myeloma (MM), reported that women in the highest category of various anthropometric measures had a 1.5- to 2.0-fold increased risk of MM, suggesting that greater adiposity may increase the risk of developing MM.1 Likewise, in the American Cancer Society Cancer Prevention Study II, the relative risk for obese subjects was around 1.5 for both sexes.2 A few other epidemiologic studies also suggested a modest increase in the risk of MM for subjects with an elevated body mass index (BMI), although the evidence is still limited and inconsistent.1 To further investigate the issue, we analyzed data from a case–control study on lymphoid neoplasms conducted in Italy between 1985 and 1997.3 This included 141 cases of incident, histologically confirmed MM (International Classification of Diseases, 9th revision code 203; 70 men and 71 women) age 38–79 years. Controls were 1112 subjects (530 men and 582 women) age 35–79 years admitted to the same hospitals as cases for a wide range of acute, nonneoplastic conditions not related to tobacco, alcohol, and long-term modifications in diet. Both cases and controls were interviewed in the hospital by trained interviewers using a standard questionnaire. Information was obtained on sociodemographic characteristics, anthropometric measures, tobacco, alcohol and coffee consumption, selected dietary items, a problem-oriented medical history, and selected occupational exposures. Study subjects were asked to report their weight and height 1 year before cancer diagnosis or interview (for controls). BMI, computed as weight/height2, was categorized into 4 levels as defined by the World Health Organization standards, ie, underweight = <18.5 kg/m2, normal weight = 18.5–24.9 kg/m2, overweight = 25.0–29.9 kg/m2, and obese = ≥30.0 kg/m2. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated by unconditional logistic regression models, including terms for age, sex, area of residence, education, year at interview, and tobacco smoking. Compared with subjects of normal weight, the ORs were 0.57 (95% CI = 0.15–2.14) for underweight, 1.43 (0.92–2.24) for overweight, and 1.57 for obese subjects (0.81–3.04) (Table). The association with BMI was consistent in the 2 sexes, although somewhat stronger in women (the OR for obese subjects was 1.30 in men and 2.26 in women).TABLE: Distribution of 141 Cases With Multiple Myeloma, and 1112 Controls, With Corresponding Odds Ratios and 95% Confidence Intervals, According to Body Mass Index, Italy, 1985–1997Although our study could have some of the limitations of hospital-based case–control studies, these should be limited given the exclusion of controls with chronic conditions potentially related to lifestyle factors, the administration of a standard questionnaire to both cases and controls under similar conditions, the same catchment area for cases and controls, and their almost complete participation. Self-reported weight and height are typically highly correlated with actual measurements, and there is no reason to suggest differential reporting by cases and controls. Furthermore, adjustment was made for potentially relevant confounding variables. The present data provide further support to the hypothesis that obesity may be related to a modest increased risk of MM. It has been suggested that obesity may affect immunologic responses that are involved in the development of MM.4,5 One alternative explanation of the association between obesity and MM risk is increased insulin resistance and consequent increased insulin-like growth factor production, which is in turn involved in the process of mitogenesis and carcinogenesis; another possible mechanism involves IL-6, produced in the bone marrow but also synthesized in adipose tissue, and involved in the proliferation and differentiation of plasma cells.6–8 However, the biologic mechanisms need to be further clarified. Cristina Bosetti Laboratorio di Epidemiologia Istituto di Ricerche Farmacologiche “Mario Negri” Milan, Italy [email protected] Eva Negri Silvano Gallus Istituto di Ricerche Farmacologiche “Mario Negri” Milan, Italy Luigino Dal Maso Servizio di Epidemiologia e Biostatistica Centro di Riferimento Oncologico Aviano (PN), Italy Silvia Franceschi International Agency for Research on Cancer Lyon, France Carlo La Vecchia Istituto di Ricerche Farmacologiche “Mario Negri” Istituto di Statistica Medica e Biometria Università degli Studi di Milano Milan, Italy

To the Editor: The issue of human immunodeficiency virus (HIV) infection-contaminated blood and blood products has long been a major health scandal in France. While an American-made blood test for HIV became available in March 1985, French government officials delayed its approval until August 1985 so that a French test could be released first. In addition, the United States began heat-treating blood products for hemophiliacs in late 1984, a year before the French adopted the practice (1). The consequences-on a public health level-of that policy have, however, not been well quantified. In 1984, two doctors in Paris (Jacques Liebowitch and Francois Pinon) had estimated that 2,500 patients per year would have received HIV-contaminated blood in France (2,3). The computation of incidence rates of AIDS in various European countries is possible by means of the European Non-Aggregate AIDS Data Set (ENAADS) made available up to March 1994 by the European Centre for the Epidemiological Monitoring of AIDS, Paris. Data are presented for Western European countries. A few countries were not included in the present analysis, either because they reported, in the period examined, <50 cases of AIDS acquired by means of blood and its products (that is, Finland, Iceland, Israel, Luxembourg, and Norway) or did not send disaggregated data to the ENAADS (that is, Ireland). Data on Germany include cases from the Federal Republic of Germany and, up to 1989, the former German Democratic Republic. The analysis presented refers to the calendar period 1985-1993. During the years considered, registration of AIDS cases had to meet the concurrent U.S. Centers for Disease Control case definition (4,5). AIDS cases were classified as hemophilic or transfusion-associated if these modes of exposure were mentioned in the AIDS report in absence of male homosexual contact and intravenous drug injection. For transfusion recipients, however, the absence of heterosexual contact with a person who had such exposures or was known to be HIV-infected was an additional requirement. Resident population estimates generally based on official censuses were obtained from the World Health Organization (WHO) database. AIDS incidence rates were computed from the number of registration cases and resident population estimates. Rates were age-standardized by the direct method, on the basis of the world standard population (6). To correct the reporting delays (that is, the lag time between the date of AIDS diagnosis and AIDS case report), the method described by Rosenberg (7) was used for the last 20 three-month periods (5 years). Additional details on the procedure used are presented elsewhere (4,8). The size of the transfusion-related AIDS epidemic up to 1993 can be derived from Fig. 1, where incidence rates for AIDS in France and other Western European countries are compared. France showed in 1985-1993, in both genders combined, the highest rate of blood-borne AIDS (3.2/1,000,000 per year) in Western Europe, 50% higher than in the second highest-risk country (Spain) and ≈3-fold higher than in the other countries, whose rates were generally close to 1/1,000,000. In 1991-1993, France had a yearly rate of transfusion-related AIDS of 3.8/1,000,000, followed by Spain (2.6) and Portugal (1.9). All other Western European countries had incidence ranging between 1.4 (Greece) and 1.0 (Germany), except the Netherlands (0.8) and Sweden (0.5). In terms of absolute figures, the estimated cumulative numbers of AIDS cases (corrected for delayed notification) among recipients of transfusions or blood products were 1,927 in France (6% of the total), followed by Spain (794, 3%), Germany (687, 6%), the United Kingdom (541, 6%), and Italy (501, 2%). The burden of HIV-contaminated blood seems to have been especially heavy on recipients of transfusions, who accounted for 78% of AIDS cases associated with blood or blood products in France. Corresponding proportions were 62% in Portugal, 54% in Italy, 37% in Germany, 34% in Spain, and 19% in the United Kingdom. With respect to hemophiliacs, more than one-eighth of the ≈3,000 hemophiliacs listed in France have been reported to have developed AIDS. Of course, the proportion of patients with AIDS who were contaminated prior to January 1985 [98% according to French government figures (1)] remains unknown. Figure 2 shows trends over time for both genders in countries with >100 cases. Incidence rates of blood-borne AIDS peaked in France in 1988-1990. Major upward trends were observed over the last 3 years in Portugal and Italy, due to the most recent spread of the AIDS epidemic in Southern Europe (4). Spain, albeit close to Italy and Portugal with respect to trends of all AIDS cases (4), shows a similarity with France with respect to trends of blood-borne AIDS. The reason for this similarity may deserve further investigation. Assuming that the excess of blood-borne AIDS observed in France, mostly in the late 1980s and early 1990s, is attributable to the different policy of management of blood and blood products, as compared with other European countries, >1,200 AIDS cases may be related to such policy in France up to 1993. The ultimate size of this epidemic remains still undetermined, but it is likely to reach 2,000-2,500 AIDS cases. Acknowledgment: We thank the national correspondents of all the countries who provided data for the European Non-Aggregate AIDS Data Set, version AIDS9403.DAT, prepared by the WHO-EC European Centre for the Epidemiological Monitoring of AIDS, Paris. This work was supported by two grants from the Ministero della Sanità-Istituto Superiore di Sanità, VII Progetto AIDS contracts 9303.12 and 9303.31, and, in part, by a grant from the European Union on STD patterns as sentinels of AIDS. *†C. La Vecchia; ‡L. Dal Maso; ‡S. Franceschi; ‡D. Serraino *Istituto di Ricerche Farmacologiche “Mario Negri”; Milan, Italy; †Istituto di Statistica Medica e Biometria, Milan, Italy; ‡Servizio di Epidemiologia; Centro di Riferimento Oncologico; Aviano (PN), Italy.FIG. 1: . Total number and age-standardized incidence rates per million population of AIDS acquired through blood or blood products in Western European countries (adjusted for reporting delay), 1985-1993.FIG. 2: . Trends of annual incidence rates of AIDS acquired through blood or blood products, by year period in some European countries, 1985-93.

Flavonoids have been associated with a reduced risk of lung, digestive tract, and certain hormone-related cancers. With reference to prostate cancer, a few epidemiological studies have found an inverse relation with intake of isoflavones, flavonols, and flavones, although the evidence remains limited and inconsistent. The role of six principal classes of flavonoids on prostate cancer was investigated using data from a multicentric case-control study conducted between 1991 and 2002 in Italy. This included 1,294 incident, histologically confirmed carcinomas of the prostate and 1,451 controls admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions. The patients' usual diet was assessed using a validated and reproducible food-frequency questionnaire; food and beverage content of six major classes of flavonoids was obtained from the U.S. Department of Agriculture. No association between prostate cancer risk was found with any of the flavonoids analyzed: the multivariate odds ratios for the highest versus the lowest quintile of intake were 0.96 (95% confidence interval, CI = 0.75-1.23) for flavanones, 1.3 (95% CI = 1.01-1.69) for flavan-3-ols, 1.23 (95% CI = 0.95-1.61) for flavonols, 1.09 (95% CI = 0.85-1.40) for flavonols, 1.18 (95% CI = 0.91-1.53) for anthocyanidins, 0.98 (95% CI = 0.76-1.26) for isoflavones, and 1.20 (95% CI = 0.92-1.58) for total flavonoids, all nonstatistically significant. Thus, the results of the present study do not support a protective effect of flavonoids on prostate cancer in this Italian population, characterized by a high intake of flavonoid-containing foods (except isoflavone-rich foods).

All ages and truncated (35 to 64 years) mortality rates from all neoplasms and from cancers of the lung, stomach, intestines, and breast for the six calendar quinquennia from 1960-1964 to 1985-1989 were computed from official death certification data and population estimates obtained from the World Health Organization database for total Europe (excluding former Soviet Union) and for three broad European areas: (a) member countries of the European Economic Community for the last period of the study; (b) other Western European countries; and (c) Eastern European countries. In Europe, mortality rates for all neoplasms increased for men and decreased for women. The increase in men can be largely explained by the major tobacco-related lung cancer epidemic throughout Europe. Lung cancer mortality rates rose steeply in Eastern Europe, where the truncated rates reached the highest levels ever observed, and there is no evidence of a leveling off. Stomach cancer mortality decreased in all Europe for both sexes, although rates remained higher in Eastern Europe, while intestinal cancer rates tended to level off around the highest values in various areas of the continent. Breast cancer showed a moderate but steady increase. Overall, the most unfavorable trends were in Eastern Europe, due to major epidemics in tobacco-related neoplasms and in other common cancers related to diet and other lifestyle habits.