The relationship between consumption of fat in seasoning and the risk of pancreatic cancer has been considered in a case-control study conducted in Italy between 1983 and 1995 on 362 pancreatic cancer cases and 1502 controls in hospital for acute, not neoplastic, non-digestive tract disorders. Subjective scores (low, intermediate, high) for the intake of butter, margarine and oil were used to evaluate the use of fat in seasoning. No material association was observed for butter or margarine. The score for oil (mainly olive oil) intake was inversely related to the risk of pancreatic cancer: the multivariate odds ratios were 0.76 for the intermediate, and 0.60 for the highest score of intake, and the trend in risk was significant. These findings support the hypothesis that (olive) oil may have a comparatively more favourable impact on the risk of pancreatic cancer than other types of seasoning fats.

The role of specific food groups and diet variety on the risk of oral and pharyngeal cancer has been considered using data from a case-control study conducted between 1992 and 1997 in the Swiss Canton of Vaud. Cases were 156 patients (126 males, 30 females) aged under 75 (median age 56) years with incident, histologically confirmed cancer of the oral cavity and pharynx, and controls were 284 subjects (246 males, 38 females, median age 57 years), admitted to the same university hospital for a wide spectrum of acute, non-neoplastic conditions unrelated to tobacco and alcohol consumption or to long-term modification of diet. After allowance for education, alcohol, tobacco and total energy intake, significant trends of increasing risk with more frequent intake emerged for eggs (OR = 2.3 for the highest tertile), red meat (OR = 2.1) and pork and processed meat (OR = 3.2). Inverse trends in risk were observed for milk (OR = 0.4 for the highest tertile), fish (OR = 0.5), raw vegetables (OR = 0.3), cooked vegetables (OR = 0.1), citrus fruit (OR = 0.4) and other fruits (OR = 0.2). The addition of a serving per day of fruit or vegetables was associated with an about 50% reduction in oral cancer risk. The most favourable diet for oral cancer risk is therefore given by infrequent consumption of red and processed meat and eggs and, most of all, frequent vegetable and fruit intake. Diet diversity was inversely related to oral and pharyngeal cancer: ORs were 0.35 for the highest tertile of total diversity, 0.24 for vegetable and 0.34 for fruit diversity. In terms of attributable risk, high meat intake accounted for 49% of oral and pharyngeal cancers in this population, low vegetable intake for 65% and low fruit intake for 54%.

The relationship between hormone replacement treatment (HRT) and breast cancer risk was considered in age-specific groups of women, combining data from two case-control studies conducted between 1983 and 1994 in six Italian centers. Cases were comprised of 5984 women, below age 75 years, with histologically confirmed breast cancer, and controls were comprised of 5504 women admitted to the hospital for a wide spectrum of acute, nonneoplastic, nonhormone-related diseases. Ever-use of HRT was reported by 6.1% of the cases and 5.5% of the controls, corresponding to a multivariate odds ratio (OR) of 1.2 [95% confidence interval (CI), 1.0-1.4]. A significant trend in risk with duration of use was observed. Separate analysis for women < 55, 55-64, and 65-74 years old at diagnosis showed that the excess risk of breast cancer associated with ever-use of HRT was not observed in the youngest age group (OR, 0.9) and increased with age at diagnosis to 1.2 (95% CI, 0.9-1.5) for women 55-64 years old and 1.6 (95% CI, 1.2-2.3) for those 65-74 years old at diagnosis. A significant trend in risk with duration was observed only in the oldest group (65-74 years old), with ORs of 1.6 (95% CI, 1.1-2.3) and 2.2 (95% CI, 1.1-4.7), respectively, for < 60 and > or = 60 months of use. Thus, this study suggests that the relationship between HRT and breast cancer risk is influenced by age at diagnosis and that any risk-benefit assessment is particularly critical for women using HRT several years after menopause.

Between 1976 and 1996, 176 borderline ovarian tumours were registered in the Cancer Registry of the Swiss canton of Vaud, corresponding to an age-adjusted incidence (world standard) of 2.7 in 100,000. Incidence rose from 1.7 per 100,000 during 1976-81 to 2.7 per 100,000 during 1987-91, and then levelled off; 58% of cases were serous and 41% mucinous. Relative survival was 94% at 10 years; 18 second neoplasms were observed, compared with 10.3 expected, and there was a significant excess of invasive ovarian cancers (four observed, including three synchronous, compared with 0.4 expected).

On the basis of clinical observations that some women with fibrocystic breast disease experienced resolution of the disease on eliminating methylxanthines from their diet, it has been suggested that coffee intake might be related to breast carcinogenesis. The relationship between coffee (mostly expresso and mocha), decaffeinated coffee and tea intake and breast cancer risk was therefore considered, combining data from two case-control studies, conducted in Italy between 1983 and 1994. Cases were 5,984 women, below age 75, with histologically confirmed breast cancer, and controls were 5,504 women admitted to hospital for a wide spectrum of acute, non-neoplastic, non-hormone-related diseases. The odds ratios (ORs) were estimated from multiple logistic regression equations including terms for study/centre, age, education, body mass index, smoking status, total alcohol intake, age at menarche and menopause, parity and age at first birth, use of oral contraceptives, use of hormone replacement therapy, history of benign breast disease and family history of breast cancer. No relationship was observed between coffee intake and the risk of breast cancer. The multivariate ORs were 1.17 (1.03-1.33), 1.17 (1.04-1.33), 1.21 (1.06-1.37) and 0.96 (0.83-1.11) for women drinking < 2, 2, > 2 to < 4 and > or = 4 cups/day compared to non-drinkers. Decaffeinated coffee was consumed only by 6-7% of cases and controls and the corresponding OR was 0.84 (0.72-0.98). Tea consumption was also low and not associated with the risk of breast cancer (OR 0.94, 95% CI 0.85-1.03). No significant heterogeneity was found for coffee intake across strata of age at diagnosis, education, body mass index, smoking status, total alcohol intake, age at menarche and menopause, parity, age at first birth, ever use of oral contraceptives, hormone replacement therapy, history of benign breast disease and family history of breast cancer. Thus, this study, based on a large data set, allows us to exclude the hypothesis that coffee intake is related to breast cancer risk in this Italian population.

It has long been suggested that subjects diagnosed with cutaneous malignant melanoma (CMM) have an excess rate of subsequent neoplasms. To provide further quantitative information on the issue, we have considered 1,780 histologically confirmed CMM diagnosed between 1974 and 1994 by the Cancer Registries of the French-speaking Swiss Cantons of Vaud and Neuchâtel (760,000 inhabitants) and followed up to the end of 1994 for the occurrence of a second primary. A total of 194 neoplasms was observed vs. 111.7 expected, corresponding to a standardized incidence ratio (SIR) of 1.7 [95% confidence interval (CI) 1.5–2.0]. When skin cancers were excluded, 87 subsequent neoplasms were observed vs. 84.9 expected (SIR 1.0). Significant excess rates were observed for basal cell (SIR 4.4), squamous cell (SIR 3.1) and melanoma (SIR 4.7) of the skin, as well as for prostatic cancer (SIR 2.1). The increased rates of subsequent skin cancer were somewhat larger in males, whereas all the SIRs were systematically greater below age 60. The SIRs of subsequent skin cancer remained above unity for 5 years or longer since diagnosis of CMM, in the absence of a clear pattern in trend with time since diagnosis. The cumulative incidence following CMM was 3% for CMM, 4% for squamous cell and 14% for basal cell carcinoma 20 years after diagnosis of CMM. Our results confirm that patients diagnosed with CMM have excess risks of subsequent melanoma and non-melanomatous skin neoplasms which justify focused prevention and surveillance of skin lesions in these patients. Subjects with CMM do not have any appreciable overall excess of non-skin neoplasms, even after long-term follow-up. Int. J. Cancer 72:776–779, 1997. © 1997 Wiley-Liss, Inc.

A recent article by Anderson et al.1 published in Cancer reported the results from a cohort study including 472 women with a history of Stein-Leventhal syndrome (SLS). No association emerged between SLS and risk of breast carcinoma (14 cases overall). SLS is characterized by menstrual irregularities, infertility, a high level of androgens, and obesity, which are clinical and hormonal conditions associated with the risk of breast carcinoma. Other studies have shown inconsistent data regarding the association between SLS and the risk of breast carcinoma.2, 3 Thus, it is also important to examine further the issue in consideration of the recent hypothesis of an association between SLS and insulin resistance and hyperinsulinemia4 (i.e., possible risk factors for breast carcinoma). Therefore, we analyzed data from a large case-control study on breast carcinoma conducted between June 1991 and February 1994 in six Italian areas: the provinces of Pordenone and Gorizia, the urban areas of Milan and Genoa, the province of Forlì in northern Italy, the province of Latina near Rome in central Italy, and the urban area of Naples in southern Italy. Study methods have been described previously.5, 6 The cases studied were 2569 women (median age 55 years; range, 23-74 years) with incident (i.e., diagnosed within 1 year before the interview), histologically confirmed breast carcinoma who were admitted to the major teaching and general hospitals in the areas under surveillance. The controls were 2588 women (median age, 56 years; range, 20-74 years) who were admitted for acute conditions (22% for traumas, 33% for other orthopedic disorders, 16% for acute surgical conditions, 18% for eye disorders, and 12% for other diseases). The structured questionnaire included information on personal characteristics and habits, education and other socioeconomic factors, general lifestyle, habits such as smoking, alcohol, and coffee consumption, a food frequency section, and menstrual and reproductive history. A past history of 23 selected medical conditions or procedures also was elicited7; among these, information was collected on history of SLS Table 1. In this data set women with breast carcinoma were significantly more educated, reported fewer full term pregnancies, and were more often premenopausal than control subjects.4 Body mass index was associated inversely with breast carcinoma risk in premenopausal women, but was directly associated in postmenopausal women.6 To allow for the possible confounding or modifying effect of these factors in the computation of the odds ratio (OR) of breast carcinoma in women with SLS, we have included in the regression equations, in addition to design variables (i.e., study area and age in quinquennia), years of education (< 7, 7-11, and ≥ 12 years), parity (0, 1, 2, 3, and ≥ 4 births), quintile of body mass index, and, when appropriate, menopausal status. The distribution of cases and controls according to history of SLS and menopausal status is shown in Table 1. A total of 14 cases (0.5%) and 16 controls (0.6%) reported a history of SLS. The OR of breast carcinoma in women with a history of SLS was 0.8 (95% confidence interval [CI] 0.4-1.7) when the whole series was considered, and 1.0 (95% CI, 0.4-2.8) and 0.8 (95% CI, 0.3-2.4), respectively, when the analysis was conducted in strata of premenopausal and postmenopausal status. The main limitation of this data set is that the diagnosis of SLS was self-reported. However, interviewers were instructed to check information in clinical records and whenever inconsistencies emerged, to reinterview the cases and controls. Despite this limitation, these data confirm the lack of an association between SLS and the risk of breast carcinoma. A more consistent association between SLS (as a cause of high unopposed estrogen levels before menopause) and risk of endometrial carcinoma has been reported.8 Therefore, hormonal factors may act on breast carcinogenesis in a different and more complex manner. Fabio Parazzini M.D.*, Carlo La Vecchia M.D. , Silvia Franceschi M.D. , Renato Talamini Sc.D.?, Eva Negri M.D.?, Pier Giorgio Crosignani Sc.D.**

Several studies suggested that frequent eating may increase colon cancer risk. To further clarify this issue, a case-control study was carried out in six areas of Italy on 1,225 incident cases < 75 years of age with histologically confirmed colon cancer and 4,154 control subjects. The controls were hospitalized for acute, nonneoplastic conditions unrelated to long-term dietary modifications. After allowance for education, physical activity, intake of vegetables, and major energy sources, there was a trend of increasing risk with increasing eating frequency (odds ratio for > or = 4 vs. < or = 2 daily meals = 1.24). Coffee intake, which was inversely associated with cancer risk, exerted a modification effect, with an odds ratio of 1.89 for frequent eaters who drank fewer than two cups of coffee per day. Frequent eating increases, whereas high coffee intake decreases, the excretion of bile acids, which are suspected to be carcinogenic to the colon. Thus, it is conceivable that frequent coffee intake may counterbalance the effect of frequent eating.

Peptic ulcer and gastrectomy are associated with an increased risk of oesophageal cancer. We considered the relation between treatment with histamine-2 (H-2)-receptor antagonists and subsequent risk of oesophageal cancer. Data from a case-control study conducted between 1984 and 1995 in northern Italy were used. These comprised 407 incident, histologically confirmed cases and 1168 controls admitted for acute, non-neoplastic, non-digestive tract conditions, unrelated to known risk factors for oesophageal cancer. Ten (2.5%) cases and 52 (4.5%) controls reported using H-2-receptor antagonists at some time, corresponding to a multivariate odds ratio (OR) of 0.5 (95% confidence interval 0.2-1.0). The OR was 0.4 for subjects who had started use seven years earlier or less, and 0.6 for those who had started use more than seven years ago. These findings indicate that risk of oesophageal cancer is not increased among H-2-receptor antagonist users. This trend to protection may be explained in terms of chance alone, or may be partly related to a possible favourable impact of H-2-receptor-antagonists on chronic oesophageal carcinogenesis.

The percent population attributable risk (AR) for breast cancer was estimated in relation to education, family history of the disease and some reproductive and hormonal factors, using data from a case-control study conducted between June 1991 and February 1994 in 6 Italian centres on 2,569 histologically confirmed incident breast cancer cases and 2,588 controls, admitted to hospital for a wide range of acute, non-neoplastic, non-hormone-related diseases. On the basis of multivariate odds ratios, a high level of education accounted for 20% of cases, elevated age at first birth and nulliparity for 38% and a family history of breast cancer in first-degree relatives for 7%. Education and nulliparity and age at first birth together explained 47% of all breast cancer cases, and the combination of these 2 factors plus a family history of the disease explained 50% of cases. In pre-menopausal women a high level of education accounted for 31% of all breast cancer cases, older age at first birth for 44% and the combination of the 2 factors for 49%. In post-menopausal women the corresponding values were 13%, 31% and 42%; further addition of risk associated with family history of the disease explained 52% of pre-menopausal cases. In post-menopausal women older age at menopause and the use of hormone replacement therapy accounted for 15% and 2% of breast cancer cases, respectively. The combination of risks associated with a high level of education, old age at first birth and nulliparity and older age at menopause accounted for 51% of cases; further inclusion of risk associated with use of hormone replacement therapy explained 52%, and the AR resulting from these 4 risk factors combined plus a family history of breast cancer was 56%. Thus, a few selected and well-identified risk factors explain about one-half the breast cancer cases in this Italian population.

The relationship between diabetes mellitus and primary liver cancer was investigated in a case-control study conducted in Italy between 1984 and 1996 on 428 cases with incident, histologically confirmed hepatocellular carcinoma, 59 with gallbladder and bile duct cancer, and 1,502 control subjects in the hospital for acute non-neoplastic diseases. Sixty-four cases of hepatocellular carcinoma vs. 87 controls reported a history of diabetes, corresponding to an odds ratio (OR) of 2.3 after allowance for age, sex and area of residence, and of 2.1 [95% confidence interval (CI) = 1.4-3.2] after further allowance for alcohol and tobacco consumption, history of hepatitis and liver cirrhosis, body mass index and history of liver cancer in first-degree relatives. The ORs were similar both for subjects diagnosed with diabetes below age 45, who most likely had insulin-dependent diabetes, and for those diagnosed later, who were likelier to have non-insulin-dependent diabetes. The OR was 2.3 for subjects whose diabetes was diagnosed <5 years before diagnosis of liver cancer, 1.9 for those diagnosed 5-9 years in advance and 2.2 for those diagnosed since 10 years or more. Five cases of gallbladder and bile duct cancer reported a history of diabetes: the corresponding OR was 1.2 (95% CI 0.5-2.9). The OR of hepatocellular carcinoma was 2.4 for males and 2.0 for females, 3.0 for subjects diagnosed with liver cancer under age 60 and 1.8 for those diagnosed at age 60 or over. None of the other covariates considered, including education, history of hepatitis, liver cirrhosis and alcohol drinking showed any meaningful modifying effect or interaction. The potential pathogenic mechanisms include liver alteration-and consequent cell proliferation-in subjects with diabetes. Thus a history of diabetes mellitus could explain about 8% (95% CI 5-11) of cases of liver cancer in this population.

Cancer mortality trends in Italy over the period 1990-94 were relatively favourable, mainly reflecting the decline in lung cancer rates in males, together with the persistent declines in gastric cancer in both sexes and in cervix uteri for women. Continuous advancements were registered for neoplasms amenable to treatment, essentially testicular cancer, Hodgkin's disease and childhood leukaemias. The major unfavourable trends were observed for non Hodgkin's lymphomas, and require therefore further monitoring, besides a clearer understanding of their determinants. Italy maintains an intermediate level of cancer mortality on a European scale, suggesting that further progress is possible, mostly for tobacco-related neoplasms in males.