It has long been suggested that a varied diet may protect against gastric cancer, in the absence, however, of definition and quantification of the issue. Thus, we considered the relationship between diet diversity (i.e., variety of food intake computed as the total number of foods consumed at least once per week) and the risk of gastric cancer using data of a case-control study conducted between 1985 and 1993 in northern Italy on 746 gastric-cancer cases below age 75 years and 2,053 controls admitted to hospital for acute, non-neoplastic, non-digestive-tract diseases. A significant inverse association was observed between various measures of food diversity and gastric cancer risk. Compared with subjects in the lowest quartile of total diversity, the multivariate odds ratios (ORs) were 0.9 for the second, 0.9 for the third and 0.7 for the highest quartiles. The inverse association was even stronger for vegetable (OR = 0.5 for the highest level) and fruit (OR = 0.6) diversity. Our findings were not explained by allowance for total calorie intake and total number of servings, besides education as an indicator of social class, and support, therefore, the concept that a more diversified and richer diet is a relevant underlying correlate of the decline in gastric cancer rates.

We considered the association between diabetes and risk of endometrial cancer using data from a large case-control study conducted in Italy. Cases were 752 women with incident, histologically confirmed endometrial cancer <75 years of age (median age 60 years, range 28–74) admitted to a network of hospitals in Milan. Controls were 2,606 patients (median age 54 years, range 25–74) aged <75 years, admitted for acute non-neoplastic, non-gynecological, non-hormone-related conditions to the same network of hospitals where cases had been identified. A total of 132 (17.6%) cases and 116 controls (4.5%) reported a history of diabetes. The corresponding multivariate odds ratio (OR) was 2.9 [95% confidence interval (CI) 2.2–3.9]. No association emerged with diabetes diagnosed under age 40 (likely to be insulin-dependent diabetes), whereas the OR of endometrial cancer was 3.1 (95% CI 2.3–4.2) for diabetes diagnosed at age ≥40 years. The OR of endometrial cancer in women with history of diabetes was 3.0 for women with a body mass index (BMI) (QI) kg/m2 <25, 3.6 for those with a BMI of 25–29, and 3.3 for those with a BMI ≥30. No consistent interaction or modifying effect was observed for any other covariate. Our results confirm that non-insulin-dependent diabetes is associated with the risk of endometrial cancer. The association may be mediated through elevated oestrogen levels in diabetic women, hyperinsulinemia or insulin-like growth factor-I (IGF-I).Int. J. Cancer 81:539–542, 1999. © 1999 Wiley-Liss, Inc.

To investigate the relation between selected micronutrients and breast cancer risk, we conducted a case-control study of breast cancer between June 1991 and April 1994 in 6 Italian areas. The study included 2569 women admitted to the major teaching and general hospitals of the study areas with histologically confirmed incident breast cancer and 2588 control women with no history of cancer, who were admitted to hospitals in the same catchment areas for acute, non-neoplastic, nongynecological conditions unrelated to hormonal or digestive tract diseases or to long-term modifications of the diet. Dietary habits, including alcoholic beverage consumption, were investigated using a validated food frequency questionnaire, including 78 foods or food groups, several types of alcoholic beverages, some "fat intake pattern" questions and some open sections for foods consumed frequently by the subject and not reported in the questionnaire. To control for potential confounding factors, several multiple logistic regression models were used. When major correlates, energy intake and the mutual confounding effect of the various micronutrients were taken into account, beta-carotene, vitamin E and calcium showed a significant inverse association with breast cancer risk. The estimated odds ratios of the 5th quintile compared to the lowest one were 0.84 for beta-carotene, 0.75 for vitamin E and 0.81 for calcium. No significant association emerged for retinol, vitamin C, thiamin, riboflavin, iron and potassium. Our results suggest that a diet rich in several micronutrients, particularly beta-carotene, vitamin E and calcium, may be protective against breast cancer.

The relationship between diabetes mellitus and the risk of colorectal cancer was investigated in a multicenter case-control study, conducted in Italy between 1992 and 1996 on 1225 cases of incident, histologically confirmed colon cancer, 728 cases of rectal cancer, and 4154 controls, who were in the hospital for acute, nonneoplastic diseases. Overall, 66 (5.4%) cases of colon cancer, 50 (6.9%) cases of rectal cancer, and 185 (4.4%) controls reported a history of diabetes. The corresponding multivariate odds ratios (ORs) were 1.2 [95% confidence interval (CI), 0.8-1.6] for colon, 1.5 (95% CI, 1.1-2.2) for rectal, and 1.3 (95% CI, 1.0-1.6) for all colorectal cancers. No association was observed for subjects who were diagnosed with diabetes at ages of < 40 years (7 cases and 27 controls, OR = 0.9). The OR was 1.4 (95% CI, 1.1-1.7) for subjects who were diagnosed with diabetes at ages of > or = 40 years and were likely to have non-insulin-dependent diabetes. The association was also stronger (OR = 1.6; 95% CI, 1.1-2.3) among subjects whose diabetes was diagnosed 10 or more years in advance and who were > or = 60 years old at the time of colorectal cancer diagnosis. None of the other covariates, including sex, education, body mass index, physical activity, energy intake, alcohol drinking, and fiber intake, showed any appreciable modifying effect. Thus, this uniquely large case-control study of colorectal cancer confirms that subjects with non-insulin-dependent diabetes mellitus have a slightly increased risk of colorectal cancer. More importantly, allowance for a large number of identified potential confounding factors, including body mass index, diet, and physical activity, could not explain the excess colorectal cancer risk among subjects with diabetes mellitus. These findings have plausible biological correlations because insulin-like-growth factor-I is a promoter of colon tumor cell growth in vitro.

Introduction ............................................................................................ 98 Descriptive Epidemiology...................................................................... 98 Cancer of the Bladder and Other Urinary Sites .................................... 99 Cancer of the Pancreas ......................................................................... 101 Cancer of the Colon and Rectum ......................................................... 102 Cancer of the Stomach and Upper Aerodigestive Tract ..................... 103 Cancer of the Breast.............................................................................. 104 Cancer of the Ovary ............................................................................. 104 Cancer at Other Sites ............................................................................ 104 Summary and Conclusions .................................................................. 105 Acknowledgments ................................................................................ 106 References ............................................................................................. 106Studies on the relationship between coffee consumption and cancer risk have been mainly focused on cancers of the urinary bladder, pancreas, and colorectum, and most data refer to adult and elderly populations. The relationship between coffee and bladder cancer is controversial, although many case-control studies have been published over the last three decades. In most studies, compared to coffee nondrinkers, the odds ratio (OR) tends to be elevated in drinkers, but the excess risk is generally neither dose nor duration related. Thus, although coffee drinking may be considered a risk indicator of bladder cancer, a strong association can be excluded, and it is still unclear whether this indicator is causal or nonspecific and due to some bias or confounding. For pancreatic cancer, a possible positive association with coffee consumption was postulated in a report published in 1981; since then, however, most studies have shown no substantial association, and, thus, there is now substantial evidence that coffee is not related to pancreatic cancer risk. Overall evidence on the coffee-colorectal cancer relation suggests an inverse association: no consistent relationship was observed in five cohort studies, but mostcase-control studies found OR below unity for colon and close to unity for rectal cancer. A plausible biological explanation has been given in terms of reduction of bile acids and neutral sterol secretion in the colon. For other cancer sites, including oral cavity, esophagus, stomach, liver, breast, ovary, kidney, and lymphoid neoplasms, data on the relation between coffee drinking and cancer risk are limited and generally inconsistent, but largely reassuring.

A history of benign thyroid diseases has been associated with the risk of thyroid cancer. We have analyzed this issue using data from a case-control study conducted in northern Italy between 1986 and 1992 on 399 incident, histologically confirmed thyroid cancer cases and 617 controls admitted to the hospital for acute, nonneoplastic, non-hormone-related diseases. The overall multivariate relative risk (RR) estimates were 2.8 [95% confidence interval (CI), 0.6-12.4] for previous episodes of thyroiditis, 27.1 (95% CI, 6.5-111.9) for adenoma, 8.2 (95% CI, 3.5-19.1) for goiter, 3.8 (95% CI, 1.4-10.9) for hyperthyroidism, and 1.5 (95% CI, 0.4-5.1) for hypothyroidism when all histotypes were analyzed. The RR for any thyroid disease was 7.7 (95% CI, 4.6-12.8). A family history of thyroid disease was significantly related to thyroid cancer with an RR of 1.6. The RR for having resided in endemic goiter areas was 1.3 for < 20 years of residence and 1.6 for 20 or more years. These associations were somewhat stronger when only papillary, follicular, and mixed papillary/follicular cancers were considered. Analyses of data in separate strata of sex and age suggested that several benign conditions play a more important role in females and in subjects younger than 50 years. Results were similar to the overall ones when papillary and follicular carcinomas were considered separately. The population-attributable risk for any previous thyroid disease was approximately 20% in this Italian population. These results confirm that history of thyroid disease is a relevant indicator of subsequent thyroid cancer risk also in areas at relatively low prevalence of goiter and other thyroid diseases.

The protection conveyed by oral contraceptives against ovarian cancer risk is one of the best established and most important features of epithelial ovarian cancer on a public health scale. Ovarian cancer incidence and mortality rates have been declining in most developed countries for women born after 1920, and the decline was greater in countries where oral contraceptive use has been more widespread. Thus, data from descriptive epidemiology are consistent with a favourable effect of oral contraceptives on ovarian cancer risks. The overall estimated protection from cohort and case-control studies is approximately 40% in ever oral contraceptive users, and increases with duration of use to more than 50% for users of 5 years or longer. The favourable effect of oral contraceptives against ovarian cancer risk persists for at least 10-15 years after use has ceased, and it is not confined to any particular type of oral contraceptive formulation. However, available data do not provide definite evidence for more recent low-dose formulations and for longer periods of latency or recency of use. The protection is also observed on borderline malignancy ovarian neoplasms, and probably on benign epithelial cysts as well. There is suggestive evidence of some protection for sex-cord-stromal cancers, but not for germ cell neoplasms. In terms of biological mechanisms, oral contraceptives are thought to act on ovarian cancer risk by affecting the lifetime number of ovulations. The protection attributable to oral contraceptives on ovarian cancer risk is one of the major issues on any individual risk/benefit assessment and public health evaluation of this type of contraceptive use.

Using data of a case-control study conducted in Italy between 1992 and 1996 on 1225 cases of colon cancer and 4154 controls, we have evaluated the effect of selected established risk factors in subjects with, and in those without, familial propensity (134 cases, 146 controls); there were non-significant associations between education and meal frequency and colon cancer risk. Physical activity, high energy and low vegetable intake were significantly related to colon cancer risk in subjects without familial predisposition, but showed no relationship in those with family history of colorectal cancer: the ORs were 1.1 for the lowest level of physical activity, 0.7 for the highest tertile of energy intake, and 1.0 for the lowest one of vegetable intake. These findings would suggest that genetic predisposition can make the influence of environmental factors for defining the risk of colon cancer weak and/or difficult to estimate.