Fertility drugs and breast and ovarian cancer.
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Biomedical subjects
Publications and source records attributed to C La Vecchia.
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OBJECTIVE: To quantify patterns and trends in incidence of AIDS associated with transfusion of blood and its products in 14 European countries and the United States. DESIGN: Data were derived from the World Health Organisation's European non-aggregate AIDS dataset and, for the United States, from the Centers for Disease Control AIDS public information dataset. Rates were standardised by using the world standard populations and adjusted for reporting delays in each country. SUBJECTS: Cases of AIDS in patients with haemophilia and recipients of transfusions. RESULTS: Overall, between 1985 and 1993 almost 6000 cases of AIDS associated with transfusions were registered in the 14 European countries considered and over 8000 in the United States between 1985 and 1992. Most European countries had annual age adjusted rates lower than 0.5 per million children aged 12 or less and between 1 and 2 per million adults. The United States had rates around 1 per million children and 5 per million adults in the most recent period. For children, the highest rates were generally reached in 1985-7, whereas in adults the highest rates were in the late 1980s. France had the highest overall incidence of AIDS related to transfusion in Europe (3.3 per million). Romania had a major epidemic in children (over 30 cases per million children in 1988-90). Incidence rates of AIDS associated with transfusion were still increasing in some southern European countries in the early 1990s. CONCLUSIONS: Apart from in France and Romania it is clear that rates of bloodborne AIDS in European countries are lower than those registered in the United States.
To investigate possible correlates of the systematically higher pancreatic cancer rates in males than in females, the role of menstrual, reproductive and hormonal factors in females have been assessed using data from a case-control study conducted in Northern Italy. Cases were 133 women with histologically confirmed incident cancer of the pancreas, and controls were 377 women in hospital for acute, non-neoplastic, non-digestive-tract disorders. After allowance for age, education, area of residence and smoking habit, an increased risk of pancreatic cancer was observed in women with early menarche (< or = 13 years) (OR = 1.9; 95% CI: 1.0-3.6), but no significant association was observed with age at menopause or length of fertile life. Parous women were at reduced risk as compared to nulliparous women (OR = 0.7), although the trend in risk with number of births was not significant. No association with spontaneous or induced abortions was observed. Pancreatic cancer risk was inversely related to early age at first birth (first birth < 25 versus nulliparae: OR = 0.5; 95% CI: 0.3-0.9; p-value for trend < 0.01) and to age at last birth (last birth < 25 versus nulliparae: OR = 0.3; 95% CI: 0.1-0.8; p-value for trend < 0.05). Ever-users of estrogen replacement therapy showed a non-significantly increased risk (OR = 2.2). Although no clear pattern of association is evident, the present results are in agreement with previous epidemiological observations and experimental research indicating that hormonal (menstrual and reproductive) factors could explain part of the male-to-female differential in incidence and mortality from pancreatic cancer.
Trends in cancer incidence and mortality in young adults (aged 20 to 44 years) over the period 1974-1992 were analyzed using data from the Vaud Cancer Registry, Switzerland. A total of 1,497 cancers were registered in males, after excluding non melanomatous skin cancers. The most common neoplasms were testis, lymphomas, lung, skin melanoma and oral cavity and pharynx. The overall age-standardized (world population) incidence was 750 per million males, and increased from 676 in 1974-1979 to 808 in 1986-1992. These upward trends were due mainly to cancers of the oral cavity and pharynx, lung, skin melanoma and colorectum, while testicular cancer rates remained stable. For females, a total of 1,899 malignant neoplasms was notified, corresponding to an overall age-standardized incidence of 914 per million. The overall rate increased from 818 in 1974-1979 to 1,003 in 1986-1992. The most frequent neoplasms were breast, skin melanoma, ovary, thyroid and lymphomas. The major types of cancer responsible for these upward trends were breast cancer, skin melanoma and lung cancer. In the period studied there were 458 cancer deaths in males and 408 in females, corresponding to an overall age-standardized rate of 227 per million males and 193 per million females. Death rates in males tended to decline, to reach 194 per million in 1986-1992, but no consistent trend was observed in females. The decline in males was essentially due to the fall in rates for testicular cancer and Hodgkin's disease. In females, falls in death rates were observed for cancer of the cervix uteri, ovary and Hodgkin's disease. Death rates were upwards for lung cancer in both sexes, and for skin melanoma and breast cancer in females.
Data from the Vaud Cancer Registry, Switzerland, were used to analyse incidence and mortality from cancer in teenagers (aged 10 to 19 years) over the period 1974-1992. A total of 113 males and 87 females were registered. Of these, 23% were lymphomas, 16% leukaemias, about 15% central nervous system neoplasms, 10% germ cell tumours and bone neoplasms and 8% soft tissue sarcomas. The overall incidence rate (age-adjusted, world standard population) for all cancers combined was 167 per million boys and 128 per million girls. In both sexes, there was some indication of rising trends over time, to reach 196 per million males and 141 per million females in 1986-1992. The only types of cancer showing consistent upward trends in both sexes were lymphomas. A total of 53 cancer deaths were certified, due to leukaemias in about 40% of cases in both sexes and to lymphomas and brain tumours in 15%-20%. The overall mortality rate at age 10-19 years (age-standardised, world standard) was 47 per million boys and 31 per million girls, and no trend in mortality was observed over time. The 2 main findings of our analysis are (i) the absence of major trends in cancer incidence in adolescents, with the sole exception of a possible increasing incidence of lymphomas, and (ii) the lack of appreciable trends in mortality, in view of the declines in cancer mortality observed in children and young adults over the same calendar period.
The proportions of gastric cancer cases attributable (or attributable risks, AR) to consumption of traditional foods (i.e., pasta, rice and maize), low intake of beta-carotene and vitamin C, short duration of use of an electric refrigerator, low educational level, and family history of gastric cancer were computed using data from a case-control study conducted in Northern Italy. Between 1985 and June 1993 a total of 746 incident, histologically confirmed gastric cancer cases and 2,053 controls admitted to the same network of hospitals for acute, nonneoplastic, non-digestive-tract diseases, unrelated to long-term modifications of diet, were interviewed. The ARs were 48% for low intake of beta-carotene, 40% for high consumption of traditional foods, and 16% for low intake of vitamin C. Overall, these 3 dietary factors explained 73% of the gastric cancer cases in the population. Five percent of all cases were attributable to less than 30 years' use of an electric refrigerator, 15% to low educational level, and 5% to family history of gastric cancer. In individuals over age 60, a greater proportion of cases was attributable to traditional foods, low education and late adoption of electric refrigeration (58% vs. 32% aged under 60), suggesting that correlates of lower social class, influenced lifestyle, and dietary habits more markedly in earlier than in more recent generations. According to our estimates, over 3 quarters of the gastric cancer cases in this area are explainable in terms of the risk factors considered. Increased consumption of vitamin C and beta-carotene, and reduced consumption of traditional foods, would help to avoid over 10,000 out of 14,000 stomach-cancer deaths in Italy every year. Consequently, stomach cancer, which is still the third leading cause of cancer death in Italy, would represent only about 2% of all cancer deaths.
The relationship between oral contraceptives (OC) and breast-cancer risk was analysed using data from a case-control study conducted between June 1991 and February 1994 in 6 Italian centres on 1,991 patients below age 65 with histologically confirmed incident breast cancer and 1,899 controls admitted to hospital for a wide range of acute, non-neoplastic, non-hormone-related diseases. "Ever OC use" was reported by 18% of cases versus 14% of controls, corresponding to a multivariate odds ratio (OR) of 1.1 (95%) confidence interval, Cl 0.9 to 1.4). The ORs were 1.3 for use lasting < 1 year, 1.1 for 1 to 4 years, 0.9 for 5 to 8 years, and 1.2 for over 8 years. With reference to age at first use, there was some indication that the OR was elevated in women who had started use before age 30, but not in those starting at a later age. With reference to time since last OC use, the OR was above unity for women who had stopped for less than 10 years (1.6 for 1 to 4 years; 1.7 for 5 to 9 years), but the OR declined to unity for women who had stopped OC use for 10 years or longer. The OR for women who had stopped OC use for less than 10 years was consistently elevated across strata of selected covariates, and was directly related to the duration of use (OR 1.3 for < 5 years, 1.7, for > or = 5 years). In contrast, the OR was 0.6, for use lasting > or = 5 years in women who had stopped for 10 years or more. The elevated OR for women who had recently stopped OC use, together with the absence of association (or the suggestion of some protection) for those who had stopped for 10 years or more is consistent with the pattern of breast-cancer risk observed after a full-term pregnancy, and provides important reassurance on a public health level on the long-term impact of OCs on breast carcinogenesis.
To determine the relationship between cigarette smoking and endometrial cancer, we conducted a case-control study. The cases were 726 patients with histologically confirmed endometrial cancers 74 years of age or less (median age, 59 years; range, 31-74) admitted between 1983 and 1992 to the Ospedale Maggiore (including the four largest teaching and general hospitals in the greater Milan area), to the Obstetrics and Gynecology University Clinics, and to the National Cancer Institute of Milan. The controls were 1452 patients younger than 75 years (median age, 59; range, 25-74) admitted for acute, nongynecological, nonhormonal, nonneoplastic conditions to the same network of hospitals where cases had been identified. Cases were less frequently ever-smokers (19%) than controls (25%). In comparison with never-smokers, the relative risk (RR) of endometrial cancer was 0.8 (95% confidence interval, CI, 0.7-1.1) in current smokers and 0.6 (95% CI 0.4-0.9) in ex-smokers. The risk of endometrial cancer decreased with number of cigarettes smoked per day and duration of habit. The estimated RR were, in comparison with never-smokers, 0.8 and 0.6 respectively in smokers of less than 20 and 20 or more cigarettes per day (chi 2(1) trend 5.48, P = 0.02) and 1.0 and 0.5 in ever-smokers for less than 20 and for 20 years or more. There was no clear relation with time since first smoking, but the RR was lower in ex-smokers who had stopped smoking less than 10 years before the interview (RR, 0.4; 95% CI, 0.2-0.8) than in those who had stopped 10 years or more before (RR, 0.8; 95% CI, 0.5-1.4). The estimated RR for ever-smokers was close to unity in premenopausal women, but apparently stronger in premenopause. Likewise the RR was 0.9 in lean (< 25 Quetelet's index) smoking women in comparison with lean nonsmokers, but smoking appeared to reduce the association with overweight. The estimated RR of endometrial cancer, in comparison with nonsmokers with Quetelet's index < 25 was 2.0 in nonsmokers with Quetelet's index > or = 25, and 1.3 in smokers with Quetelet's index > or = 25. These findings confirm the role of smoking on endometrial cancer risk. The risk reduction is, however, moderate in relative terms, and negligible from a public health point of view, in consideration of the negative consequences of smoking in several other diseases.
METHODS: The changes in patterns of smoking initiation in Italian males and females in 1955, 1965, 1975, and 1985 were analyzed using data from the 1990-1991 Italian National Health Survey, based on a sample of 18,483 males and 19,320 females ages 19 to 59. The sample was randomly selected within strata of geographic area and size of place of residence and of household in order to be representative of the general Italian population. The age of each subject was reconstructed for each calendar year of interest (1954 to 1956, centered on 1955, 1964 to 1966, 1974 to 1976, and 1984 to 1986). For each calendar period and year of age of interest (14 to 24), the numerator of the smoking initiation rate was the number of subjects who started smoking and the denominator was the number of subjects at risk, i.e., nonsmokers of the same age. The same procedure was repeated for three separate age groups (14 to 17, 18 to 20, and 21 to 24). RESULTS: Among males, there was a trend toward earlier age at start of smoking and higher initiation rates between 1955 and 1965, and a subsequent decline in initiation rate, particularly at age 18 or over and during the last calendar decade studied. In females, between 1955 and 1975 there was an increase of over fourfold in initiation rates and systematic tendencies toward earlier age at starting; only over the past decade have the starting rates begun to decline. The peak rate was reached at age 18-20 for males in 1965 (53.3%) and for females in 1975 (23.9%). CONCLUSION: The recent declines in smoking initiation have been relatively limited among the younger age groups, and this reflects an earlier average age at smoking initiation.
BACKGROUND: Information on a possible relation between coffee, caffeine, and other methylxanthine-containing beverages and hip fracture is relatively scanty and controversial. We present here the results of a case-control study conducted in northern Italy. METHODS: A total of 279 cases of hip fracture and 1,061 controls in hospital for acute, nonneoplastic nontraumatic, non-hormone-related diseases were interviewed during their hospital stay. Odds ratios (OR) and their 95% confidence intervals (CI) according to consumption of coffee and other methylxanthine-containing beverages were derived from multiple logistic regression equations including terms for age, education, body mass index, smoking status, alcohol drinking, calcium intake, menopausal status, and estrogen replacement therapy. RESULTS: Compared with nondrinkers, the OR was 1.2 (95% CI, 0.8 to 1.7) for coffee drinkers. No association emerged with number of cups/day (OR = 1.2 for 1 cup/day, 1.0 for 2, 1.4 for 3 and 4, and 1.2 for 5 or more cups/day) or with duration of coffee intake (OR = 1.0 for less than 30 years and OR = 1.1 for more than 30 years). Similarly, no statistically significant association was observed with decaffeinated coffee (OR = 1.3), tea (OR = 1.3), or cola intake (OR = 0.6). OR for coffee drinking were computed across strata of age, menopausal status, education, smoking status, total alcohol drinking, and calcium intake. CONCLUSIONS: The present study found no association between hip fractures among women and consumption of regular or decaffeinated coffee, tea, and cola.
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The relationship between frequency of consumption of eleven indicator foods (milk, meat, liver, carrots, green vegetables, fruit, eggs, ham, fish, cheese and alcohol) and serum cholesterol was investigated in the comparison group of a case-control study of acute myocardial infarction conducted in Italy. Data were collected on 792 subjects from various Italian regions, admitted to hospital for acute conditions unrelated to any known or potential risk factor for myocardial infarction or to long-term modifications in diet. No statistically or epidemiologically meaningful relationship emerged between serum cholesterol level and frequency of consumption of any of these foods. Cholesterol levels rose according to increasing consumption tertiles for most of the indicator foods considered. Higher values for the higher tertile of consumption were observed for meat, ham and eggs, but also for fruit, carrots and green vegetables. However, correlation coefficients between frequency of consumption of various food items and serum cholesterol level were uniformly low for all food items considered, ranging between -0.09 (for milk) and 0.19 (for ham). Although a more comprehensive diet history may lead to different indications, the present data are not suggestive of any major influence of long-term frequency of consumption of a few selected indicator foods on serum cholesterol levels.
Recent trends in mortality from lung cancer in Europe are reviewed. During the last decade, overall lung cancer mortality in males showed no systematic pattern in Northern and Central Europe, but a modest decline started at younger ages in several countries. In Southern Europe, lung cancer mortality started from lower values, but is still rising, and only in Italy is some flattening of rates at relatively high levels becoming apparent in middle age (35-64 years). The average change in lung cancer rates in Southern Europe over the last decade for males was + 24% for all ages and + 22% in middle age. The upward trends were even more substantial in Eastern European countries (+ 32% in middle age), which now have the highest lung cancer rates in young and middle-aged males. Over the last few decades, female lung cancer rates have risen in all European countries, but only in Denmark and Britain are overall rates now over 20/100,000. There is therefore still ample scope for urgent intervention aimed at controlling a major tobacco-related lung cancer epidemic among European women in the near future. Southern and mainly Eastern Europe are becoming priority areas for campaigns for giving up smoking, since the prevalence of tobacco smoking in the young is higher and high-tar dark-tobacco cigarettes are still common.
Age-standardised mortality rates for childhood cancers for the calendar period 1950-1989 were reviewed for 22 countries (Canada, U.S.A., 10 Latin American countries or territories, Egypt, seven countries or territories from Asia, Australia and New Zealand) using data from the World Health Organization database. The highest mortality rates (between 6 and 7.5/100,000 boys, between 5 and 6/10,000 girls) for all childhood neoplasms were registered in Latin American countries (Uruguay, Cuba, Argentina, Costa Rica), Kuwait, New Zealand and Singapore. Rates were low in most developed countries, such as Canada, U.S.A., Australia, Japan and Israel (3.5 to 4.5/100,000). The pattern was similar for leukaemias, which account for approximately 50% of all childhood cancer mortality. From the 1960s onwards, a 50% decline in childhood cancer mortality was observed in the U.S.A. and Canada, and substantial declines were also observed in other developed countries, such as Australia, Israel and Japan. The pattern was much less favourable for other areas of the world, including Latin America and a few countries from Asia for which there were data. These declines in childhood cancer mortality are essentially attributable to improved management of the disease. The delay observed in the decline in mortality for most developing countries emphasises the scope and the importance of extending adequate treatments for childhood cancers to these areas of the world.
Trends in mortality rates from gallstones and other nonneoplastic gallbladder and biliary tract diseases between 1955 and 1990 for 38 countries (8 from America, 3 from Asia, 25 from Europe, Australia, and New Zealand) were analyzed. Age-adjusted mortality rates standardized on the world population were computed from official death certifications derived from the World Health Organization database. There were generalized and substantial declines in the rates in both sexes and all countries considered, except for males in Czechoslovakia and Poland. Over the calendar period considered, the average declines were over 70% for males and over 80% for females in North America, over 60% for males and 70% for females in Latin America, although mortality remained relatively high in Chile. The declines were 80% for both sexes in Japan and over 70% for males and 80% for females in Australia. The pattern was more heterogeneous in Europe, with decreases of approximately 70 to 80% in northern Europe, but more modest in central and southern Europe, with particularly moderate downward trends for males. In several countries the decreases were rather steady over the calendar period considered, but in a few others the decline was restricted or larger during the most recent calendar period. The trends in gallstone and other gallbladder disease mortality in various areas are affected by differences and potential biases in death certification reliability, and by underlying variations and changes in the prevalence of gallstones and gallbladder surgical removal. A likely interpretation for the generalized decline in mortality over the last calendar period is, however, improved diagnosis and treatment of gallstone disease.
The relationship between cataract extraction in women and current body mass index, history of clinically relevant obesity, diabetes, hypertension, and hyperlipidemia was considered in a case-control study conducted in northern Italy. A total of 287 women who had cataract extraction and 1227 control subjects who were in the hospital for acute, nonneoplastic, nonophthalmologic, nonmetabolic, nongastroenterologic diseases were interviewed during their hospital stay. Odds ratios (ORs) and their 95% confidence intervals (CIs) were derived from multiple logistic regression equations, including terms for age, education, smoking status, current body mass index, and simultaneously the four diseases considered. Elevated current body mass index (OR, 2.2; 95% CI, 1.2 to 3.8, for > or = 30 versus < 20 kg/m2), diabetes (OR, 2.2; 95% CI, 1.4 to 3.4), hypertension (OR, 1.5; 95% CI, 1.1 to 2.0), hyperlipidemia (OR, 1.8; 95% CI, 1.2 to 2.7), and clinical history of obesity (OR, 1.5; 95% CI, 1.0 to 2.2) were associated with an increased risk of cataract extraction. The OR in two separate strata of age (< 60 and > or = 60 years) indicated that the associations of diabetes and hyperlipidemia were stronger at a younger age: the OR for diabetes was 4.6 for those younger than 60 years and 1.7 for those age 60 or over, and for hyperlipidemia the ORs were 2.8 and 1.6, respectively. Thus, the results of this study support the association in women between cataract extraction and diabetes, current overweight, history of clinically relevant obesity, hypertension, and hyperlipidemia. These findings also suggest that these factors may have some biologically independent impact on the risk of cataract.
The relationship between past contraceptive method use and risk of ectopic pregnancy has been analyzed in a case-control study conducted in Milan, Italy. Cases were 158 women with diagnosis of ectopic pregnancy confirmed by laparoscopy or laparotomy, admitted to a network of university and general hospitals of Milan. The first control group (obstetric controls) included 243 women who gave birth at term (more than 37 weeks' gestation) to healthy infants at the same hospitals where the cases had been identified. The second control group (non-obstetric controls) was a random sample of 158 women admitted to the same network of hospitals where cases had been identified for diseases other than malignant, hormonal, or gynecological in origin. A total of 37 (23%) cases, 21 (9%) obstetric and 24 (15%) non-obstetric controls reported ever IUD use. The corresponding relative risk, RR, of ectopic pregnancy was 3.5 (95% CI 1.3-4.6) when non-obstetric subjects were considered as control group. The risk of ectopic pregnancy increased with duration of IUD use: in comparison with obstetric and non-obstetric controls, the RR were 2.3 and 2.0 for users for less than 2 years and 4.3 and 2.6 for longer users. There was no clear relation between time since last IUD use and risk of ectopic pregnancy, and no evidence of a decline of risk with increasing time since stopping use.(ABSTRACT TRUNCATED AT 250 WORDS)
Risk factors for benign ovarian teratomas have been analysed in a case-control study conducted in Milan. Cases were women aged less than 65 years with a histologically confirmed diagnosis of benign ovarian teratoma who were admitted to a network of Obstetrics and Gynecology Departments in Milan. A total of 77 women aged 16-64 years were interviewed. Controls were women admitted to hospital for acute, non-gynaecological, non-hormonal and non-neoplastic diseases; 231 controls were interviewed (age range 15-64 years). Cases tended to be more educated: in comparison with women with less than 7 years of education, the estimated relative risk (RR) of ovarian benign teratoma was 1.6 and 2.5 respectively in women with 7-11 and 12 or more years of schooling, the trend in risk being statistically significant (chi 2(1) trend 5.39, P < 0.01). Four of the 77 cases (5.2%) and two of the 231 controls (0.9%) reported a history of infertility, with a corresponding RR of 8.3 (95% confidence interval 1.3-54.0). There was no clear relation between parity and risk of ovarian benign teratomas: in comparison with nulliparae, the estimated RRs were 1.1 and 0.7 respectively in women reporting one or two or more births (chi 2(1) trend 0.53, P = not significant). No relation emerged between marital status, age at menarche, menstrual cycle pattern, menopausal status, abortions, age at first pregnancy, oral contraceptive use and risk of ovarian benign teratomas.