<h3>To the Editor.—</h3> Blot et al¹provide comprehensive data on an increasing incidence of adenocarcinomas of the esophagus and gastric cardia, confirming previous clinical and epidemiologic observations. The Cancer Registry of the Canton Vaud (covering approximately 530 000 inhabitants in the French-speaking part of Switzerland) has had a specific interest in esophageal adenocarcinomas derived from a privileged situation in terms of traditional attention and careful endoscopic and histopathologic examinations of esophageal lesions.²Average annual age-adjusted (on the world standard population) incidence rates for various histological types of esophageal cancers in two separate calendar periods (1976 through 1981 and 1982 through 1987) are given in the Table. In men, there was a decline for squamous cell carcinomas (from 7.2 to 5.2 per 100 000) but a significant rise for adenocarcinomas (from 0.4 to 1.6 per 100 000;<i>P</i>&lt;.01). Rates for other or unspecified cancers also are increasing. No

Screening has a relevant role in and is likely to become an increasingly important instrument for cancer control in the near future. This overview summarizes some of the available evidence on the issue. Some of the opinions are well established. The apparent absence of consensus on other issues should be critically evaluated, too, because the evidence on some procedures is substantially more convincing than that on others. High costs, low compliance, poor curability, and substantial false positive rates, in a disease as relatively rare as cancer, often counterbalance in practice the theoretical benefits of diagnostic anticipation. In screening as well as in treatment for cancer, it is unlikely that major technical breakthroughs will occur in the near future. The evaluation of whether the benefits likely to be achieved by the screening program outweigh its disadvantages by a sufficient margin, therefore, should rely on large and carefully planned controlled studies.

The relationship between cancer risk and frequency of consumption of green vegetables and fruit has been analyzed using data from an integrated series of case-control studies conducted in northern Italy between 1983 and 1990. The overall dataset included the following histologically confirmed cancers: oral cavity and pharynx, 119; oesophagus, 294; stomach, 564; colon, 673; rectum, 406; liver, 258; gall-bladder, 41; pancreas, 303; larynx, 149; breast, 2,860; endometrium, 567; ovary, 742; prostate, 107; bladder, 365; kidney, 147; thyroid, 120; Hodgkin's disease, 72; non-Hodgkin lymphomas, 173; myelomas, 117; and a total of 6,147 controls admitted to hospital for acute non-neoplastic conditions, unrelated to long-term dietary modifications. Multivariate relative risks (RR) for subsequent tertiles of vegetable and fruit consumption were derived after allowance for age, sex, area of residence, education and smoking. For vegetables, there was a consistent pattern of protection for all epithelial cancers, with RRs in the upper tertile ranging from 0.2 for oesophagus, liver and larynx to 0.7 for breast. All the trends in risk were in the same direction and significant for all carcinomas except gall-bladder. In contrast, no protection was afforded by high vegetable consumption against non-epithelial lymphoid neoplasms. With reference to fruit, strong inverse relationships were observed for cancers of the upper digestive and respiratory tract, with RRs in the upper tertile between 0.2 and 0.3 for oral cavity and pharynx, oesophagus and larynx relative to the lowest tertile. The lower the location of the tumour in the digestive tract, the weaker appeared to be the protection afforded. Significant inverse relationships were observed for liver, pancreas, prostate and urinary sites, but not for rectum, breast and female genital cancers or thyroid. No relationship emerged for lymphomas and myelomas. Even in the absence of a clear biological interpretation, the consistency and strength of the patterns observed indicate that, in this population, frequent green vegetable intake is associated with a substantial reduction of risk for several common epithelial cancers, and that fruit intake has a favourable effect, especially on upper digestive cancers and, probably, also on urinary tract neoplasms.

The objective of this study was to assess the association between alcohol drinking before and during pregnancy and the risk of spontaneous abortion using data from a case-control study conducted in Milan, Italy. A total of 462 women (median age 30 years) were admitted for spontaneous abortion (within the 12th week of gestation) to a network of obstetrics departments in the greater Milan area. Of these, 148 (32%) were between the fourth and the eighth week of gestation and 314 (68%) between the ninth and the 12th week. A control group was made up of 814 women (median age 29 years) who gave birth at term (> 37 weeks gestation) to healthy infants (Apgar 5th minute > or = 8, weight > or = 3000 g) on randomly selected days at the same hospitals where cases had been identified. A total of 212 cases (46%) and 355 controls (47%) reported alcohol drinking before conception. Considering non-drinkers as the reference category, the relative risks (RR) of spontaneous abortion were 1.2 [95% confidence interval (CI), 0.9-1.6] and 0.8 (95% CI, 0.6-1.1), respectively, in drinkers of one to seven and more than seven drinks per week before conception. No association emerged between the duration of alcohol drinking and the risk of spontaneous abortion. A total of 166 cases (35.9%) and 263 (32.3%) controls reported any alcohol drinking during the first trimester of pregnancy. The corresponding relative risk was 1.1 (95% CI, 0.9-1.4) and no relationship emerged between the number of drinks per week and the risk of abortion.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract The role of age at menarche and at menopause on epithelial ovarian cancer risk was re‐assessed in a combined analysis of 3 hospital‐based case‐control studies conducted in Italy, the United Kingdom and Greece, which produced a total of 1, 140 cases and 2,724 controls. In the overall dataset, there was no evidence of an association with age at menarche: compared with women whose menarche occurred at age I5 or over, the relative risk (RR) estimates were 1.0[95% confidence interval (CI) 0.8 to 1.2] for those with menarche at ages 12 to 14, and 1.0 (95% CI 0.8‐1.2) for those with menarche below age 12. There was no consistent interaction between age at menarche and study centre or age at diagnosis. In relation to age at menopause, compared with women whose menopause occurred at age 44 or earlier, the RR was 1.4 between 45 and 49, 1.6 between 50 and 52 and 1.9 above 52. The strength of the association was apparently (but not significantly) greater in the British than in the Greek or Italian dataset. The effect of age at menopause tended to be long‐lasting and, if anything, to increase across subsequent age‐groups. The large dataset, and the replication of results in different studies, provide more definite and precise information than previously available on the absence of appreciable effect of age at menarche on subsequent ovarian cancer risk in developed countries. For age at menopause, there was a direct and consistent trend in risk, but the association was relatively weak, with RRs below 2 even between extreme categories.

1Servizio di Epidemiologia, Centro di Riferimento Oncologico, Via Pedemontana Oce, 33081 Avtano, Italy 2Registre Vaudois des Tumeurs, Institut Universitaire de Médecine Sociale et Préventive, Centre Hospitalier Universitaire Vaudois. Lausanne, Switzerland 3Istituto di Ricerche Farmacologiche 'Mario Negri', and 4Istituto di Statistica Medica e Biometria. Università di Milano, Milan, Italy Correspondence to S Franceschi Fax: (+39) 434 659 222.

The relationship between farming and cancer risk was investigated in an integrated series of case-control studies conducted from 1985 to 1991 in the Friuli Venezia Giulia region, north-east Italy. Patients with cancer of the oral cavity and pharynx, larynx, oesophagus, colon and rectum, pancreas, breast, thyroid gland, kidney and urinary tract, bladder, prostate, soft-tissue sarcomas, Hodgkin's diseases, non-Hodgkin's lymphomas and multiple myelomas, and controls admitted to hospital for acute, non-neoplastic conditions, were interviewed. For males, a significantly elevated relative risk was seen for oral cavity and pharynx. Farming, however, was associated with a significant protection against cancer of the colon and rectum and bladder. In females, only one significant association emerged, for multiple myeloma. A few significant interactions between cancer risk and year of birth (i.e., before 1930 or 1930 and after) were observed. The risk of cancer of the larynx was significantly elevated in younger male farmers but not in older ones. Our multi-site case-control study confirms that farmers have, for some cancer sites, a distinctive pattern. Excesses of cancer of the oral cavity and pharynx in farmers are characteristic of the present study area and, possibly, of similar European rural populations who have in common high levels of alcohol consumption and, at least in the past, unbalanced diets.

The relationship between selected urinary tract and genital diseases and the risk of bladder cancer was analyzed using data from a case-control study of 364 cases of bladder cancer and 447 controls hospitalized for acute, nonneoplastic, nongenital tract conditions, unrelated to known or suspected risk factors for bladder cancer. Cystitis was reported by 20% of the cases and 8% of the controls, corresponding to a multivariate relative risk (RR) of 3.8 (95% confidence interval, 2.4 to 5.9). No association was observed with urinary tract stones (RR = 1.2). With reference to genital diseases, the RR was elevated for gonorrhea (RR = 2.8, 95% confidence interval, 1.0 to 4.5) and condylomata acuminata (RR = 5.9, 95% confidence interval 1.0 to 3.6) but not for syphilis. The risk increased with the number of episodes of cystitis (RR = 5.0 for greater than or equal to 4 episodes, chi 2 for trend = 33.04, P less than 0.001), was higher during the last 15 years after the first episode (RR = 5.1 versus 2.3 for over 15 years), and was not heterogeneous across strata of age and sex. The interaction between urinary tract infections and tobacco appeared multiplicative, with RR = 2.4 for ever smoking, 3.2 for cystitis alone, and 10.3 for both exposures. The present study, besides providing further quantitative evidence of a relationship between urinary tract infections (and, possibly, some genital infections, too) and bladder cancer, indicates that the role of infections is probably in one of the latter (promoting) stages of the process of carcinogenesis and suggests a multiplicative interaction with smoking. In terms of prevention and public health, therefore, it is thus important to avoid at least one exposure for subjects with a history of urinary tract infections who smoke tobacco.