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).

To assess the dietary correlates of cancer of the ovary, the consumption of a wide range of food groups has been investigated in a case-control study conducted between January 1992 and September 1999 in 4 Italian areas. Cases were 1,031 women with incident, histologically confirmed epithelial ovarian cancer; controls were 2,411 women admitted to the same network of hospitals as the cases for acute, non-malignant and non-gynecological conditions, unrelated to hormonal or digestive tract diseases or to long-term modifications of diet. The subjects' usual diet was investigated through a validated food frequency questionnaire including 78 foods and recipes, then grouped into 18 food groups. Odds ratios (OR), and the corresponding 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models including terms for age, study center, education, year at interview, parity, oral contraceptive use and energy intake. Our knowledge on risk factors of ovarian cancer is mainly related to hormonal and reproductive factors, and include nulliparity, late age at menopause, family history of ovarian and breast cancer, and infrequent oral contraceptive (OC) use. 1 Diet has been suggested to have a potential influence on ovarian carcinogenesis, although dietary associations have not yet been established and well quantified, and only scattered data from epidemiological studies are available. 2 Descriptive epidemiology and ecological studies have reported positive relations between fats, proteins and total calories intake and ovarian cancer risk. 3,4 Data from analytical, mainly casecontrol studies, also supported the hypothesis of a possible increased risk in relation to various types of fat, 5-10 but not with monounsaturated ones. 11 With reference with specific foods, several case-control studies reported a beneficial effect of diet rich in vegetables on ovarian cancer risk. 7,10,12,13 A few case-control studies showed that women with cancer of the ovary reported more frequent meat consumption, 8,10,14 and others suggested that high egg intake may also increase the risk of ovarian cancer. 6,7,9 Fish, on the other hand, seemed to exert a protective effect. 6,8,15,16 The evidence of an association between these foods and cancer of the ovary is, however, inadequate.Ovarian cancer also has been reported to be correlated with per capita milk consumption and lactase persistence, 17,18 and it has been hypothesized that lactose, or its component sugars, may be responsible for this association. 17 Other investigations, however, did not support the hypothesis that galactose plays a role in the development of ovarian cancer, 12,19 -21 and suggested that any potential association between milk consumption and ovarian cancer may be due to the fat content of milk. 16,22,23 To better assess the dietary correlates of cancer of the ovary, the consumption of a wide range of food groups has been investigated in a uniquely large hospital-based case-control study conducted in Italy. MATERIAL AND METHODSA multicentric...

Background:Hepatocellular carcinoma (HCC) has been associated to diabetes and obesity, but a possible association with the metabolic syndrome (MetS) and its potential interaction with hepatitis is open to discussion.Methods:We analysed data from an Italian case–control study, including 185 HCC cases and 404 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from unconditional logistic regression models.Results:Among the MetS components, diabetes and obesity (i.e, body mass index (BMI)⩾30 kg m−2) were positively associated to HCC risk, with ORs of 4.33 (95% CI, 1.89–9.86) and 1.97 (95% CI, 1.03–3.79), respectively. The ORs for the MetS were 4.06 (95% CI, 1.33–12.38) defining obesity as BMI⩾25, and 1.92 (95% CI, 0.38–9.76) defining it as BMI⩾30. The risk increased with the number of MetS components, up to an almost four-fold excess risk among subjects with ⩾2 MetS factors. Among subjects without chronic infection with hepatitis B and/or C, the OR for those with ⩾2 MetS components was over six-fold elevated. There was no consistent association in subjects with serological evidence of hepatitis B and/or C infection.Conclusion:This study found that the risk of HCC increases with the number of MetS components in subjects not chronically infected with hepatitis viruses.

Mortality rates of hepatocellular carcinoma (HCC) are high in Italy compared with other Western countries. To elucidate further the role of hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol drinking, and tobacco smoking in the etiology of HCC, we carried out a hospital-based case-control study in two areas of Italy: the province of Pordenone in the Northeast and the town of Naples in the South. A total of 229 HCC cases (median age, 66 years) and 431 controls (median age, 65 years) answered a questionnaire and provided blood samples between 1999 and 2002. Odds ratios (OR), percent attributable risks, and corresponding 95% confidence intervals were computed using unconditional multiple logistic regression. ORs for hepatitis B surface antigen (HBsAg) positive versus HBsAg negative and for anti-HCV antibody positive versus anti-HCV antibody negative were 20.2 and 15.6, respectively. Positivity for both markers was associated with an OR of 51.6. Sensitive molecular techniques applied to sera in a subset of HCC cases disclosed a very small number of occult hepatites. Maximal lifetime alcohol intake of z35 versus <7 drinks/wk was associated with an HBV/ HCV adjusted OR of 5.9. Tobacco smoking was unrelated to HCC risk overall but seemed to enhance HCC risk among virus carriers. Overall, 61% of HCC were attributable to HCV, 13% to HBV, and 18% to heavy alcohol drinking. In conclusion, our study confirms the importance of HCV in HCC etiology in Italy where the widespread dissemination of the virus dates back four or five decades. (Cancer Epidemiol Biomarkers Prev 2006;15(4):683 -9)