Inspection of the age-incidence curve of ischaemic heart disease in both sexes shows an increase in slope for women around the menopause, approaching that of men at older ages. Although the increase is likely to be related to the menopause, epidemiological evidence is not defined. Likewise, there is some suggestion that reproductive factors may be related to the subsequent risk of cardiovascular diseases, since a few studies found an elevated risk in women with an earlier first birth. In terms of prevention and public health considerations, treatments via exogenous hormones are, however, much more important. A systematic overview of the available epidemiological evidence indicates that oestrogen replacement treatment is protective against ischaemic heart disease. The overall relative risks based on 18 studies and greater than 3300 cases was 0.81, with a narrow 95% confidence interval (0.76-0.85), thus suggesting a protective effect of 15-25%. This protection has a plausible biological interpretation in terms of increased high density lipoprotein (HDL) levels. The serum lipoprotein pattern can be unfavourably influenced by progestin supplementation. With reference to oral contraceptives, the relative risk for cardiovascular mortality was increased about twofold in current users. There appears now to be convincing evidence that the elevated risk is restricted to current users.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between education, social class, smoking habits, alcohol consumption and the risk of digestive tract neoplasms was analysed in a case-control study of 50 cases of cancer of the mouth or pharynx, 209 of the oesophagus, 397 of the stomach, 455 of the colon, 295 of the rectum, 151 of the liver, 214 of the pancreas, and a total of 1944 control subjects admitted for acute, non-neoplastic or digestive tract disorders. Cancers of the mouth or pharynx, oesophagus and stomach were inversely and strongly related to education, with risk estimates ranging between 0.2 and 0.4 for the highest education categories. Significant, but weaker inverse relations were evident for rectal and liver cancer, too, whereas the risk of colon cancer was elevated among more educated individuals. There was no relationship between education and pancreatic cancer. The pattern of risk was largely comparable when the head of the household's occupation was used as indicator of social class. There were strong direct associations between cigarette (as well as pipe or cigar) smoking and cancers of the mouth or pharynx and oesophagus, and a moderate one with pancreatic cancer, but none of the other sites considered was related to smoking habits. Cancers of the mouth or pharynx and oesophagus were independently and strongly related to alcohol consumption, too, while the associations between alcohol and liver or pancreatic cancer were moderate and not significant. Cancers of the stomach, colon and rectum were unrelated to measures of alcohol consumption.

A population-based case-control study of gallbladder cancer was conducted in the south-west of Poland, within the frame-work of the SEARCH Programme of the International Agency for Research on Cancer. A total of 73 cases and 186 controls were interviewed using a questionnaire including demographic and socio-economic factors, education, smoking, alcohol, tea and coffee consumption, and past medical history. A validated diet history was used to estimate the daily intake of calories, fats, carbohydrates, proteins, cholesterol, fibres and vitamins C and E. Gallbladder disease was the major determinant of subsequent gallbladder cancer: 41 cases (56%) vs. 15 (8%) controls had a past history of gallbladder disease, corresponding to an odds ratio (OR) of 12.5 (95% confidence interval, 5.8 to 26.6), and the OR was 12.1 for gallbladder problems dating back 20 years or more in the past. There was an inverse relationship with education, the OR being 0.3 (95% CI 0.1 to 1.2) for 13 years of education or more vs. less than 7. Gallbladder cancer risk was positively associated with total calorie intake, with ORs of 1.4, 1.5, 4.1 for the 3 upper quartiles compared with the lowest one (trend, p less than 0.01). Weaker direct associations were observed for proteins, carbohydrates and cholesterol. There was some suggestion of inverse associations with fibre intake, and a more consistent one with vitamins C and E. These results further quantify the role of gallstones, and suggest that total calorie intake and other dietary factors potentially linked with benign gallbladder conditions are involved in the aetiology of gallbladder cancer.

Adams and Morris1 found that preoperative cimetidine induced a positive lymphocyte response in 5 of 24 colorectal carcinoma patients not treated with cimetidine and in 10 of 18 carcinoma patients treated with the drug, and suggested that cimetidine antagonized histamine inhibition of lymphocyte function at a histamine H2 receptor by increasing lymphocyte infiltrate in human colorectal carcinoma.1 They had also previously shown that cimetidine administered preoperatively improved the survival of colorectal carcinoma patients, suggesting a protective role of cimetidine against intestinal carcinogenesis.2 However, this finding is still uncertain both in humans3, 4 and in laboratory animals.5 A 10-year postmarketing surveillance of the safety of cimetidine reported significant excess mortality (RR = 2.7, based on 35 deaths) in the first year. However, this leveled off with time, and the point estimates for colorectal carcinoma were not significantly below unity after 5 years.6 Thus, the data on a possible relation between cimetidine therapy and colorectal carcinogenesis are still inconclusive. Therefore, we assessed the relation between cimetidine use and the risk of colorectal carcinoma in a large case-control study carried out in Northern Italy between 1985 and 1991.7 The cases comprised 955 patients with incident, histologically confirmed carcinoma of the colon (498 men and 457 women; median age, 61 years; range, 20-79 years) and 639 with carcinoma of the rectum (380 men and 259 women; median age, 62 years; range, 20-79 years). Controls comprised 2909 patients (1880 men and 1029 women; median age, 58 years; range, 19-79 years) admitted to the same hospitals for various acute conditions not related to digestive tract diseases or to known or likely risk factors for colorectal carcinoma. A total of 29 cases of colon carcinoma (3.0%), 17 cases of rectal carcinoma (2.7%), and 106 controls (3.6%) reported use of cimetidine (Table 1). The multivariate odds ratios (ORs) were 0.9 for colon carcinoma and 0.8 for rectal carcinoma. There was no relation with time since the first use of the drug: the OR for colon carcinoma was 0.8 for use that began either ≤7 or >7 years earlier, and the ORs for rectal carcinoma were 0.7 and 1.0 for use that began ≤7 or >7 years earlier, respectively. Thus, these findings rule out a major relation between cimetidine use and colorectal carcinoma risk, although they are compatible with a moderate favorable effect. Alessandra Tavani*, Francesca Fioretti*, Silvia Franceschi , Carlo La Vecchia

The observation of similar changes in distribution for benign and malignant tumors may suggest the importance of improved diagnostic accuracy (particularly total colonoscopy) for lesions arising in the proximal colon.

This study indicates that a family history of MI is an independent risk factor for MI, and that the number of relatives and the age at which they were affected is related to the strength of the association. There is a multiplicative effect on RR between family history and several major risk factors for MI.

When disease control depends on technologically advanced medical care, as in the case of cancer, the North American population is benefited by earlier and effective introduction of new therapeutic approaches. This conclusion does not apply to other childhood diseases, the incidence of which is higher among low-income groups and control of which depends on prevention rather than treatment.

We conducted a study on 91 women with thyroid cancer and 306 controls in hospital for acute nonneoplastic, non-hormone-related disorders in order to investigate the role of reproductive and hormonal factors in the etiology of epithelial thyroid cancer in the Canton of Vaud, Switzerland. Non-significant increases in cancer risk with an increasing number of full-term pregnancies (odds ratio, OR, after allowance for age and previous benign thyroid disease = 1.6, for > or = 3 vs. 0 full-term pregnancies, 95% confidence interval, CI: 0.7-3.6) and spontaneous abortions (OR = 2.0 for > or = 2 vs. 0 spontaneous abortions, 95% CI: 0.7-5.2) were seen. A significantly elevated OR (2.8, 95% CI: 1.1-7.2) was found in those women whose first pregnancy ended with an abortion. Whereas most other reproductive, menstrual and hormonal factors examined did not seem to affect the risk of thyroid cancer significantly, a clue emerged of an association between thyroid cancer and artificial menopause (OR = 6.3, for women who underwent artificial menopause vs. premenopausal women, 95% CI: 1.7-23.2). Although not necessarily causal, the relationship between the risk of epithelial thyroid cancer and the occurrence of spontaneous abortions and artificial menopause deserves attention in future studies, in the light of the high incidence of thyroid cancer in young and middle-aged women.

Dal Maso, Luigino*; Lo Re, Angelo*; Braga, Claudia*; La Vecchia, Carlo†; Franceschi, Silvia* Author Information

Caesarean section rates in Italy in the early 1980s were still lower than in North America, but their determinants share several similarities with those reported in other areas.

The relation between dietary factors and the risk of colorectal cancer was investigated in a case-control study conducted in Pordenone province, North-eastern Italy, on 123 cases of colon cancer, 125 of rectal cancer and 699 controls admitted to hospital for acute, non-neoplastic or digestive disorders. Consistent positive associations were observed with more frequent consumption of bread (odds ratio, OR = 2.1 for colon and 2.2 for rectum for highest vs. lowest tertile), polenta (OR = 2.1 for colon, 1.9 for rectum), cheese (OR = 1.7 for colon, 1.8 for rectum) and eggs (2.5 for colon, 1.9 for rectum), whereas reduced ORs were observed in subjects reporting more frequent consumption of tomatoes (OR = 0.5 for colon and 0.4 for rectum). High consumption of margarine exerted a significant protection against cancer of the colon whereas high consumption of carrot spinach, whole-grain bread and pasta (favorably) and red meat (unfavorably) affected rectal cancer risk in particular. Thus the present study gives support for a protective effect associated with a fiber-rich or vegetable-rich diet, while it indicates that frequent consumption of refined starchy foods, eggs and fat-rich foods such as cheese and red meat is a risk factor for colo-rectal cancer.

This study suggested that, although none of the differences in the effects between cancer sites was statistically significant, tobacco from pipes and cigars and the cleansing effect of some foods of plant origin and nonalcoholic beverages may influence the risk of cancer of the tongue less strongly than the risk of cancer of the mouth.

In a case-control study conducted between May 1979 and February 1980, in Milan, Italy, to evaluate risk factors for ovarian cancer, various reproductive and menstrual characteristics, marital status, education, history of various diseases, and lifetime drug use were examined among 161 women with histologically proven epithelial cancer and 561 controls. Early menarche, late menopause, low parity, late age at first pregnancy and total ovulatory years were associated with an increased risk of ovarian cancer. The elevated risk associated with late age at first pregnancy was not accounted for by low parity. Many of the risk factors identified in this study are also accounted for by low parity. Many of the risk factors identified in this study are also related to the risk of adenocarcinoma of the endometrium and to breast cancer. Further exploration of these factors may lead to an improved understanding of the etiology of all three cancers.

The relation between family history of ovarian, breast, and endometrial cancer and risk of epithelial ovarian carcinoma was analyzed within the framework of a case-control study conducted from 1983 to 1989. The study included 755 cases of ovarian cancer and 2,023 controls in hospital for a spectrum of acute nongynecologic, hormonal, or neoplastic conditions in the Greater Milan area, Italy. Eighteen cases (2%) and 24 controls (1%) reported a history of ovarian cancer in a first-degree relative: The corresponding multivariate adjusted odds ratio (OR) was 1.9 (95% confidence interval (CI) 1.1-3.6). The risk of ovarian cancer was elevated in women reporting a family history of breast cancer (OR = 1.6, 95% CI 1.1-2.3), but no significant association emerged with a family history of endometrial cancer (OR = 1.3, 95% CI 0.8-1.7). When the data were stratified by family history of breast cancer, a family history of ovarian cancer was over 10 times more frequent in both cases and controls who reported a family history of breast cancer than in cases and controls reporting no family history of breast cancer. The estimated odds ratio for ovarian cancer associated with a family history of the disease was 2.3 (95% CI 1.1-4.5) in women not reporting a family history of breast cancer, but no association emerged in the subgroup of women reporting a family history of breast cancer. These results confirm that a family history of ovarian cancer increases the risk of the disease, but the percentage of ovarian cancer cases explained by a family history of the disease is small: Less than 1% of observed cases in this study could be attributed to this "family risk factor."