A major protective mechanism against oxidizing substances capable of damaging DNA integrity and initiating carcinogenesis is the induction of phase II detoxification and antioxidant enzymes by chemopreventive agents. A key finding in the field of chemoprevention has been the discovery that the induction of these enzymes is mediated by the cytoplasmic oxidative stress system (Nrf2-Keap1). Under basal (reducing) conditions, Keap1 anchors the Nrf2 transcription factor within the cytoplasm, targeting it for ubiquitination and proteasome degradation, thus repressing its ability to induce phase II genes. When cells are exposed to chemopreventive agents and oxidative stress, however, a signal involving phosphorylation and/or redox modification is transmitted to the Nrf2-Keap1 complex, leading to its dissociation and the nuclear translocation of Nrf2, which, after hetero-dimerically partnering with other transcription factors, binds to the AREs/EpREs present within phase II gene promoters, increasing their transcription. These data should assist in developing new phase II detoxification enzyme inducers as cancer chemopreventive agents within the clinical environment.

Because of their several biological activities, flavonoids may have an important role in explaining the protective effects of vegetables, fruit, and, possibly, tea against cancer. The potential relation between flavonoids and colorectal cancer risk was investigated using data from a multicentric Italian case-control study, including 1,953 cases of colorectal cancers (1,225 colon cancers and 728 rectal cancers) and 4,154 hospital controls admitted for acute nonneoplastic diseases. We have applied recently published data on the composition of foods and beverages, in terms of six principal classes of flavonoids, on dietary information collected through a validated food-frequency questionnaire. Odds ratios (OR) were estimated by multiple logistic regression models, including terms for sex, age, study center, family history of colorectal cancer, education, alcohol consumption, body mass index, physical activity, and energy intake. A reduced risk of colorectal cancer was found for increasing intake of isoflavones (OR, 0.76, for the highest versus the lowest quintile, P trend = 0.001), anthocyanidins (OR, 0.67, P trend < 0.001), flavones (OR, 0.78, P trend = 0.004), and flavonols (OR, 0.64, P trend < 0.001). No significant association was found for flavan-3-ols (OR, 0.98), flavanones (OR, 0.96), and total flavonoids (OR, 0.97). The estimates did not substantially differ for colon and rectal cancers, as well as in strata of sex, age, and body mass index. The findings of this large study provide support for an inverse association of selected classes of flavonoids with colorectal cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1555 -8)

The present study provides further evidence that obesity and DM increase HCC risk and that these factors may explain a relevant proportion of cases among subjects without markers of HBV/HCV infection.

Previous studies have shown that various dietary components may be implicated in the aetiology of prostate cancer, although the results remain equivocal. The possible relationship of inflammation derived from dietary exposures with prostate cancer risk has not been investigated. We examined the ability of a newly developed dietary inflammatory index (DII) to predict prostate cancer risk in a case–control study conducted in Italy between 1991 and 2002. A total of 1294 patients aged <75 years with incident, histologically confirmed carcinoma of the prostate served as cases. A total of 1451 subjects aged <75 years who were admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions served as controls. The DII was computed based on dietary intake assessed using a previously validated seventy-eight-item FFQ. Logistic regression models were used to estimate multivariable OR adjusted for age, study centre, years of education, social class, BMI, smoking status, family history of prostate cancer and total energy intake. Men with higher DII scores had a higher risk of prostate cancer when analysed using the DII as both continuous (OR 1·06, 95 % CI 1·00, 1·13) and categorical, i.e. compared with men in the lowest quartile of the DII, men in the third and fourth quartiles were at elevated risk (ORQuartile 3 v. 1 1·32, 95 % CI 1·03, 1·69 and ORQuartile 4 v. 1 1·33, 95 % CI 1·01, 1·76; Ptrend = 0·04). These data suggest that a pro-inflammatory diet, as indicated by the increasing DII score, is a risk factor of prostate cancer in Italian men.

Few epidemiologic studies have investigated the potential relation between flavonoids and breast cancer risk. We have applied recently published data on the composition of foods and beverages in terms of six principal classes of flavonoids (i.e., flavanones, flavan-3-ols, flavonols, flavones, anthocyanidines, and isoflavones) on dietary information collected in a large-case control study of breast cancer conducted in Italy between 1991 and 1994. The study included 2,569 women with incident, histologically confirmed breast cancer, and 2,588 hospital controls. Odds ratios (OR) and 95% confidence intervals were estimated by multiple logistic regression models. After allowance for major confounding factors and energy intake, a reduced risk of breast cancer was found for increasing intake of flavones (OR, 0.81, for the highest versus the lowest quintile; P-trend, 0.02), and flavonols (OR, 0.80; P-trend, 0.06).