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.
<p>Supplementary Table 1, Supplementary Figures 1 and 2</p>
B-cell maintenance depends on two key survival signals, one delivered through the BAFF receptor, the other through the B cell antigen receptor (BCR). While it is undisputed that the BAFF receptor signals through the alternative NF-κB signaling pathway, the nature of the BCR-mediated survival signal is controversial. Recent evidence shows, however, that the BCR signals mature B-cell survival through the PI3K pathway (Srinivasan et al., 2009). BCR-dependent PI3K activation is also required for the mitogenic response of B-cells to ligands binding innate receptors like TLRs and CD40. This receptor crosstalk integrates mechanisms of innate and adaptive immunity in the B-cell response. Epstein-Barr-Virus (EBV), a B-cell transforming herpes virus endemic in human populations worldwide, uses the BCR-dependent survival signal and CD40 co-stimulation for its interference with B cell physiology, in that the EBV proteins LMP2A and LMP1 mimic a constitutively active BCR and CD40 co-receptor, respectively. Thus, LMP2A, whose prime activity is PI3K activation, can drive B-cell development and homeostasis in mice as efficiently as the BCR. In the case of LMP1, however, B-cell specific expression induces an immune surveillance mechanism, through which LMP1-expressing B-cells are eliminated by T- and NK-cells, akin to the immune elimination of EBV-infected cells in humans. Evidence will be presented that when this surveillance mechanism is compromised, LMP1-driven B-cell lymphomas rapidly arise in transgenic mice as a fatal disease. Thus, conditional expression of a single EBV protein, LMP1, models the immune surveillance of EBV-infected cells and EBV-driven B-cell lymphomagenesis, establishing a pre-clinical model for therapeutic intervention.
The relation between smoking habits and selected chronic diseases was evaluated from the data of the 1983 Italian National Health Survey, based on 72,284 people aged 15 or over randomly selected within strata of geographical area, size of place of residence and of the household in order to be representative of the whole Italian population. The prevalence of all the 19 diseases or groups of diseases considered was elevated among ex-smokers, thus suggesting that the presence of any chronic condition stimulates cessation of smoking. The excess prevalence among ex-smokers was particularly large for myocardial infarction and other heart diseases. Four groups of diseases were positively related with current as well as with past cigarette smoking. These were chronic bronchitis, emphysema of the lung or respiratory insufficiency, gastroduodenal ulcer and varicose veins or haemorrhoids. For all these groups of diseases the relative risks were higher in heavy cigarette smokers. Compared with never smokers, the point estimates for subjects smoking 15 cigarettes per day or more were 2.6 for chronic bronchitis, 1.7 for emphysema of the lung, 2.1 for gastroduodenal ulcer and 1.6 for varicose veins or haemorrhoids. For bronchitis, ulcer and varicose veins or haemorrhoids the relative risks tended to be higher in younger and middle age groups. From these data, it was estimated that in the whole of Italy a total of about 900,000 prevalent cases of chronic bronchitis, 270,000 of emphysema, 610,000 gastroduodenal ulcers and 380,000 varicose veins or haemorrhoids could be associated with cigarette smoking.(ABSTRACT TRUNCATED AT 250 WORDS)
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 role of anthropometric variables in the risk of breast cancer has been investigated using pooled data from 2 hospital-based case-control studies conducted in Italy for a total data-set of 3,247 cases and 3,263 controls. No association was observed in pre-menopausal women between breast cancer risk and height, weight, indices of body mass (W/H2; W/H1.5) and surface area. In post-menopausal women, the risk of breast cancer was inversely related to height, being 0.8 in taller women (greater than 165 cm) compared with women 155 cm tall or less; the trend in risk, although not constantly decreasing, was statistically significant (p trend = 0.03). A direct, statistically significant association emerged with weight and indices of body mass and post-menopausal breast cancer risk. Considering 2 indices of body weight (W/H2 and W/H1.5) and relative to thinner women, the respective estimated risks of post-menopausal breast cancer increased to 1.4 and 1.3 for grossly obese women, and the corresponding p values for trend were respectively 0.002 and 0.02. The role of overweight was more evident in women with early age at menopause, thus suggesting a duration-risk effect.
