The relationship between maize consumption and risk of cancer of the upper digestive tract was investigated in 107 patients with oral cancer, 107 with pharyngeal cancer, 68 with esophageal cancer, and 505 hospital controls who permanently resided in Pordenone Province in the northeastern part of Italy. The analysis was restricted to males. The population of this province has a high incidence of these neoplasms and shows particularly elevated levels of alcohol and tobacco use, in addition to high maize consumption. Highly significant associations with frequent intake of maize emerged for oral cancer, pharyngeal cancer, and esophageal cancer (odds ratios = 3.3,3.2, and 2.8, respectively). The risk elevation could not be explained in terms of differences in education, occupation, tobacco use, or consumption of fresh fruits and vegetables. The unfavorable effect of maize on risk of cancer of the upper digestive tract, however, was evident only in those individuals who reported heavy drinking (i.e., 2*42 alcoholic drinks/ wk). The present findings are likely to be related to the fact that maize can cause deficiencies of various micronutrients (chiefly, niacin and riboflavin) and agree with previous observations from Africa, the People's
In view of the persisting uncertainty concerning possible mechanisms by which high vegetable and fruit intake decreases cancer risk, foods with divergent values for potentially important micronutrients are a priority for investigation. Tomatoes are low in beta-carotene, but high in lycopene, an active antioxidative agent. In order to assess the effect of tomatoes on risk of cancers of the digestive tract, data were analyzed from an integrated series of case-control studies conducted between 1985 and 1991 in northern Italy, where tomato intake is high but, also, heterogeneous. The overall dataset included the following histologically confirmed cancer cases: oral cavity and pharynx, 314; esophagus, 85; stomach, 723; colon, 955; and rectum, 629; and a total of 2,879 controls admitted to hospital for acute non-neoplastic or non-digestive conditions, unrelated to long-term dietary modifications. Multivariate odds ratios (OR) and 95% confidence interval (CI) for subsequent quartiles of intake of raw tomatoes were derived, after allowance for age, sex, study center, education, smoking and drinking level, and tertile of total caloric intake. There was a consistent pattern of protection for all sites (OR in the upper quartile ranging between 0.4 and 0.7), most notably for gastrointestinal neoplasms. All trends in risk were highly significant. The beneficial effect of raw tomatoes in this population may be partly due to the fact that they constitute perhaps the most specific feature of the Mediterranean diet. However, if it is true that tomatoes protect against digestive-tract cancers, this is of interest from both a scientific and a public health viewpoint.
A hospital-based case-control study of renal cell cancer was conducted in northern Italy between 1986 and 1989, with 240 cases of renal cell cancer (150 males and 90 females), and 665 controls (445 males and 220 females) chosen on the basis of age, sex, and area of residence. No associations were found between renal cell cancer and: body mass index (BMI); number of cigarettes smoked; age at starting to smoke; years of smoking; consumption of wine, beer, spirits, coffee, decaffeinated coffee; tea; intake of animal protein, fruits, and vegetables; various reproductive factors; hormonal use; sexual habits; sexually transmitted diseases; or selected occupational exposures. The odds ratio (OR) was above unity in smokers (OR = 1.34 for greater than or equal to 15 cigarettes/day), but the trends in risk with dose or duration were not statistically significant. Significant positive associations were found between renal cell cancer and sources of fat intake, especially margarine (OR for highest vs lowest intake = 1.71), and oils (OR = 1.89) whereas carrot intake showed a negative association (OR = 0.62). Also, a history of nephrolithiasis and multiple episodes of cystitis showed weak positive associations (OR = 2.00, 95 percent confidence interval (CI) 1.07-3.73; and OR = 1.60, 95 percent CI 0.95-2.70, respectively).
Frequent mutations of coding nucleotide repeats are thought to contribute significantly to carcinogenesis associated with microsatellite instability (MSI). We have shown that shortening of the poly(T) 11 within the polypyrimidine stretch/accessory splicing signal of human MRE11 leads to the reduced expression and functional impairment of the MRE11/NBS1/RAD50 complex. This mutation was selectively found in mismatch repair (MMR) defective cell lines and potentially identifies MRE11 as a novel target for MSI. Here, we examined 70 microsatellite unstable primary human cancers and we report that MRE11 mutations occur in 83.7 and 50% of the colorectal and endometrial cancers, respectively. In the colorectal cancer series, mutated MRE11 is more frequently associated with advanced age at diagnosis and A/B stages. Biallelic mutations were present in 38.8% of the cases and more frequently associated with lower (G1/G2) grade tumors. Impaired MRE11 expression was prevalent in primary colorectal tumors with larger and biallelic shortening of the poly(T)11. Immunohistochemistry confirmed the impaired MRE11 expression and revealed NBS1-defective expression in MRE11 mutated cancers. Together with the observation that perturbation of the MRE11/NBS1/RAD50 complex predisposes to cancer, our work highlights MRE11 as a new common target in the MMR deficient tumorigenesis and suggests its role in colorectal carcinogenesis
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