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BACKGROUND: The potential association between fertility drugs and risk of ovarian cancer has been analysed using data from a case-control study conducted between January 1992 and September 1999 in four Italian areas. METHODS: Cases were 1031 women (median age 56, range 18-79 years) with incident, histologically confirmed epithelial ovarian cancer. Controls were 2411 women (median age 57, range 17-79 years) residing in the same geographical areas and admitted to the same network of hospitals for cases for a wide spectrum of acute, non neoplastic, non hormone-related conditions. RESULTS: A total of 15 cases and 26 controls reported use of fertility drugs. The corresponding odds ratio (OR) was 1.3 (95% confidence interval 0.7-2.5). The OR was 1.2 for women reporting last use < 25 years before interview and 1.3 for > 25 years. CONCLUSIONS: Considering calendar year at use, the OR was non-significantly above unity for women reporting fertility drug use after 1970, The OR was 0.6 among nulliparous women and 1.9 among parous ones.

The relation between coffee and alcohol intake and ovarian cancer risk was analyzed in a case-control study conducted in Italy between 1992 and 1999. Cases were 1,031 women, aged 18-79 years, with incident, histologically confirmed invasive epithelial ovarian cancer, and controls were 2,411 women, aged 17-79 years, admitted to the hospital for acute nonneoplastic non-hormone-related diseases. Coffee intake (mostly espresso and mocha) was not associated with ovarian cancer risk, with an odds ratio (OR) of 0.93 [95% confidence interval (CI) = 0.69-1.27] in drinkers ofor = 4 cups/day compared with drinkers of1 cup/day. No meaningful relation was observed with cappuccino (OR = 1.06, 95% CI = 0.85-1.32 for drinkers compared with nondrinkers), decaffeinated coffee (OR = 0.64, 95% CI 0.42-0.96), and tea intake (OR = 0.90, 95% CI = 0.75-1.08). Total alcohol intake was not associated with ovarian cancer risk (OR = 1.09, 95% CI = 0.76-1.57 in drinkers ofor = 36 g/day compared with never drinkers). No relationship was found with wine (OR = 1.03, 95% CI = 0.70-1.50 for39 g/day compared with never drinkers), beer, amari, grappa, and spirits. No significant heterogeneity was found for coffee or total alcohol intake across strata of age, education, parity, oral contraceptive use, family history of ovarian/breast cancer, body mass index, and calorie intake. This study, based on a large data set; provides no support for a causal association between invasive epithelial ovarian cancer risk and coffee and alcohol intake.

The relationship between oral contraceptives (OC) and breast-cancer risk was analysed using data from a case-control study conducted between June 1991 and February 1994 in 6 Italian centres on 1,991 patients below age 65 with histologically confirmed incident breast cancer and 1,899 controls admitted to hospital for a wide range of acute, non-neoplastic, non-hormone-related diseases. "Ever OC use" was reported by 18% of cases versus 14% of controls, corresponding to a multivariate odds ratio (OR) of 1.1 (95%) confidence interval, Cl 0.9 to 1.4). The ORs were 1.3 for use lasting1 year, 1.1 for 1 to 4 years, 0.9 for 5 to 8 years, and 1.2 for over 8 years. With reference to age at first use, there was some indication that the OR was elevated in women who had started use before age 30, but not in those starting at a later age. With reference to time since last OC use, the OR was above unity for women who had stopped for less than 10 years (1.6 for 1 to 4 years; 1.7 for 5 to 9 years), but the OR declined to unity for women who had stopped OC use for 10 years or longer. The OR for women who had stopped OC use for less than 10 years was consistently elevated across strata of selected covariates, and was directly related to the duration of use (OR 1.3 for5 years, 1.7, foror = 5 years). In contrast, the OR was 0.6, for use lastingor = 5 years in women who had stopped for 10 years or more. The elevated OR for women who had recently stopped OC use, together with the absence of association (or the suggestion of some protection) for those who had stopped for 10 years or more is consistent with the pattern of breast-cancer risk observed after a full-term pregnancy, and provides important reassurance on a public health level on the long-term impact of OCs on breast carcinogenesis.During June 1991-February 1994 in Italy, researchers conducted a case control study to examine the association between oral contraceptive (OC) use and breast cancer risk. Cases comprised 1991 women aged less than 65 with confirmed breast cancer. Controls included 1899 same-age patients at the same network of hospitals as the cases with an acute, non-neoplastic, non-hormone-related condition. 18% of cases and 14% of controls had ever used OCs. Overall, there was no association between OC use and breast cancer. Very short term OC use (1 year) had an odds ratio (OR) of 1.3 (borderline significance only). Recall or selection bias may have accounted for this moderate association. However, women who had recently stopped using OCs faced an elevated risk of breast cancer (OR = 1.6 for 1-4 years since last OC and 1.7 for 5-9 years). This elevated risk remained above unity across strata of selected covariates (education, age at menarche, parity, age at 1st birth, no history of breast cancer, and history of benign breast disease). Among women who had last used OCs 10 years ago, the risk of breast cancer was directly related to duration of use (OR = 1.3 for 5 years and 1.7 for =or 5 years; p = 0.02 [for the trend]). The OR for women who had last used an OC longer than 10 years ago reached unity. Among these women, those that used OCs for at least five years had a lower risk of developing breast cancer (OR = 0.66). Women who started using OCs before age 30 had a somewhat elevated risk of developing breast cancer (OR = 1.3 for 25 years and 1.4 for 25-29 years). The increased OR for women who had recently ceased using OCs and the apparent protection against breast cancer among women who ceased using OCs for at least 10 years match the pattern of breast cancer risk noted after a full-term pregnancy. These findings should reassure the public that OCs apparently do not induce breast carcinogenesis.

BACKGROUND: Approximately 5-10% of breast cancers are hereditary and their biology and prognosis appear to differ from those of sporadic breast cancers. In this study we compared the biological features and clinical characteristics of non metastatic breast cancer in patients with BRCA mutations versus patients with a family history suggesting hereditary breast cancer but without BRCA mutations (BRCA wild type) versus patients with sporadic disease, and correlated these findings with clinical outcome. METHODS: We retrieved the clinical and biological data of 33 BRCA-positive, 66 BRCA-wild type and 1826 sporadic breast cancer patients contained in a single institution clinical database between 1980 and 2012. Specifically, we recorded age, tumor size, nodal status, treatment type, pattern of relapse, second primary incidence, outcome (disease-free survival and overall survival), and biological features (estrogen receptor [ER], progesterone receptor [PgR], tumor grade, proliferation and c-erbB2 status). Median follow-up was 70 months. RESULTS: BRCA-positive patients were significantly younger than sporadic breast cancer patients, and less likely to be ER-, PgR- or c-erbB2-positive than women with BRCA-wild type or sporadic breast cancer. Tumor size and grade, nodal status and proliferation did not differ among the three groups. Rates of radical mastectomy were 58, 42 and 37%, and those of conservative surgery were 42, 58 and 63% in women with BRCA-positive, BRCA-wild type and sporadic breast cancer (p = 0.03), respectively. The incidence of contralateral breast cancer was 12, 14 and 0% (p

Some studies report an increased risk of autoimmune thyroid disease in hepatitis C and B as well as in interferon therapy. Recently a new link between HCV and papillary thyroid cancer has been published. The mechanism responsible for the oncogenetic role of HCV is not well understood, but it involves immunity system and autoimmunity disorders. We designed a case-control study on HCV exposure. To assess the positivity to HCV ELISA test and polymerize chain reaction technique (PCR) were used. For statistical analysis an odds ratio and corresponding 95% confidence intervals were computed using unconditional multiple-logistic-regression models. Our findings show a statistically significant association between HCV and papillary thyroid cancer (OR = 3.3, 95% CI 1.5-7.4, p=0.003), overall in female gender (OR = 3.3, 95% CI 1.2-8.7, p=0.01) and in the > or =50 years age category the risk for thyroid cancer was confirmed by the OR = 3.2 (95% CI 1.3-7.9, p=0.01). Based on our study there is an association between HCV and thyroid cancer and it is more readily detectable in countries with a high prevalence of HCV.

The aim of this study was to evaluate the activity and toxicity of a double biochemical modulation of 5-fluorouracil (5-FU) by means of methotrexate (MTX) and levo-folinic acid (LFA) in patients with advanced carcinoma of the digestive tract, and to assess the prognostic significance of MTX serum concentrations achieved in these patients. 94 patients affected by advanced carcinoma of the colon-rectum, stomach or biliary tract (47 of them previously untreated) received a regimen consisting of MTX 500 mg/m2 as a 2-h i.v. infusion on day 1, followed by LFA 250 mg/m2 as a 2-h i.v. infusion and 5-FU 600 mg/m2 as an i.v. bolus on day 2. Cycles were repeated every 2 weeks. Treatment was administered until tumour progression or for a maximum of 24 courses. MTX serum level was assessed soon after and 24 h (24-h MTXs) after its infusion in 61 patients. One complete and 22 partial responses were obtained, giving an overall activity of 24% (95% confidence interval, 16-34%). Response rate was 30% in chemotherapy-naive patients (colorectal, 26%; gastric, 37%; and biliary-tract, 22%) and 19% in those previously treated (all with fluoropyrimidines). A poor performance status adversely affected the response and survival of patients. The toxicity of treatment was very mild, and occurrence of severe diarrhoea (11% of patients) and mucositis (3%) was lower than that reported with other modulations of 5-FU. A cut-off value of 24-h MTXs was identified as a strong prognostic indicator. Patients with 24-h MTXs > or = 2 microM had a significantly better probability of response (37% versus 5%; P = 0.032), longer progression-free survival (5.3 versus 2.3 months; P = 0.023) and overall survival (10.8 versus 8.3 months; P = 0.045) on multivariate analysis. In chemotherapy-naive colorectal cancer patients, those with 24-h MTXs > or = 2 microM had a response rate of 38% (3/8), with a 19.6-month median survival time, as compared to no responses (0/4) and a 9.9-month median survival in the group with a lower serum concentration. The achievement of such MTX serum levels yielded a 31% (4/13) response rate even in colorectal patients who had previously received a 5-FU-FA treatment.

We investigated the relationships between risk of colon and rectal cancers and physical activity in both sexes at different ages by a case-control study conducted between 1991 and 1996 in six Italian centres. Cases were 1225 patients (688 men, 537 women) below the age of 75 with colon cancer and the controls included 4154 patients (2073 men, 2081 women) admitted to hospital for acute, non-neoplastic conditions. We also analysed 722 cases of rectal cancer. Compared with the lowest level of occupational physical activity at 30–39 years old the odds ratios (OR) for the highest level were 0.64 (95% confidence interval, CI 0.44–0.93) in men and 0.49 (95% CI 0.33–0.72) in women. The inverse association in both sexes was similar at 15–19 and 50–59 years old. No association was found in either sex for leisure-time physical activity. For both sexes the inverse relationship between occupational physical activity at 30–39 years old and colon cancer risk was not significantly heterogeneous across strata of selected covariates, and for ascending, transverse, descending and sigmoid colon. Rectal cancer risk was not associated with any measure of physical activity (OR = 1.32 for men and 0.88 for women for the highest level of occupational physical activity at 30–39 years old compared with the lowest). This study confirms that occupational physical activity is protective against colon, but not against rectal cancer. © 1999 Cancer Research Campaign

The incidence and number of deaths caused by pancreatic tumours have been gradually rising, while the incidence and mortality of other common cancers have been declining. Risk factors for this malignant disease include cigarette smoking, family history of chronic pancreatitis, advancing age, male sex, diabetes mellitus, obesity, non-0 blood group, a high-fat diet, alcohol consumption and possibly Helicobacter pylori and hepatitis B virus infections. Metabolic diseases have become the leading cause of death in many countries. Our paper serves as a focused and updated discussion about the development of novel preventive strategies for this deadly disease. Abbreviations. ARE: antioxidant response element; COX-2: cyclooxygenase-2; IGFs: insulin-like growthfactors; IGF1R: IGF-1 receptor; MetS: metabolic syndrome; NAFLD: non-alcoholic fatty liver disease;NAFPD: non-alcoholic fatty pancreas disease; NASH: non-alcoholic steatohepatitis; NASP: non-alcoholic steatopancreatitis; PPARγ : peroxisome proliferator-activated receptor γ; PPARs: peroxisome proliferatoractivated receptors.

Aims and BackgroundThe aim of the present study was to determine, retrospectively, whether the immunohistochemical expression of two biologic markers of aggressivity, P-glycoprotein (P-gp) and PCNA/cyclin (PCNA), could be related to response to chemotherapy and prognosis in locally advanced breast cancer.MethodsPC 10 Mab was used to determine the proliferation index (PCNA) and C-219 Mab to determine P-gp in 25 locally advanced breast carcinomas subjected to preoperative chemotherapy with MDR-related drugs.ResultsP-gp and PCNA were expressed in 76 % and 100 % of the tumors, respectively. No case of high P-gp expression was associated with good chemosensitivity, and all P-gp-negative cases showed the best chemotherapeutic response. P-gp and PCNA were both highly expressed in patients who developed local-regional or distant metastases. No recurrence was associated with a negative or low P-gp score.ConclusionsStatistical analysis showed that high P-gp expression was related to a poor response to chemotherapy and a short disease-free survival. A high PCNA score was not found to be significant for predicting chemosensitivity or survival.

Dietary deficiency of folate and other micronutrients involved in the one-carbon metabolism (i.e., vitamins B2, B6, B12, and methionine) have been related to several diseases, including cancers, but results on non-Hodgkin lymphoma (NHL) are controversial. A hospital-based case-control study was conducted in Italy, in 1999-2002. Cases were 190 incident, histologically confirmed NHL aged 18-84 years. Controls were 484 subjects admitted to hospitals for acute, non-neoplastic diseases supposed to be unrelated to alcohol consumption or to diet modification. Dietary habits, including alcohol drinking, were assessed by a validated food-frequency questionnaire. Nutrient intakes were computed using the Italian food composition database. Odds ratios (ORs) and corresponding 95% confidence intervals for tertiles of nutrients' intake were computed using the energy-adjusted residual models. No significant association emerged between NHL risk and intakes of folate (OR=0.9), vitamin B2 (OR=0.9), vitamin B6 (OR=0.8), and methionine (OR=0.7). However, a significant inverse association was observed for all the nutrients examined among abstainers and former drinkers, whereas no relations between one-carbon nutrients and NHL risk emerged among current alcohol drinkers. Our findings support the possibility of an antagonist effect of alcohol on the one-carbon metabolism in NHL etiology. However, the lack of an overall effect for one-carbon nutrients and the small sample size suggested caution in interpreting our results.

Background Metabolic Syndrome (MS) has been correlated to breast carcinogenesis. MS is common in the general population (34%) and increases with age and body mass index. Although the link between obesity, MS and hormone related cancer incidence is now widely recognized, the molecular mechanisms at the basis of such increase are still poorly characterized. A crucial role is supposed to be played by the altered insulin signalling, occurring in obese patients, which fuels cancer cell growth, proliferation and survival. Therefore we focused specifically on insulin resistance to investigate clinically the potential role of insulin in breast carcinogenesis. Methods 975 patients were enrolled and the association between MS, insulin resistance, and breast cancer was evaluated. Women were stratified by age and menopausal status. Insulin resistance was measured through the Homeostasis Model Assessment score (HOMA-IR). The cut off value to define insulin resistance was HOMA-IR ≥ 2.50. Results Higher prevalence of MS (35%) was found among postmenopausal women with breast cancer compared to postmenopausal healthy women (19%) [OR 2.16]. A broad range of BMI spanning 19–48 Kg/m2 was calculated. Both cases and controls were characterized by BMI ≥ 25 Kg/m2 (58% of cases compared to 61% of controls). Waist circumference >88 cm was measured in 53% of cases - OR 1.58- (95% CI 0.8-2.8) and in 46% of controls. Hyperinsulinemia was detected in 7% of cases – OR 2.14 (95% CI 1.78-2.99) and only in 3% of controls. HOMA-IR score was elevated in 49% of cases compared to 34% of controls [OR 1.86], suggesting that insulin resistance can nearly double the risk of breast cancer development. Interestingly 61% of women operated for breast cancer (cases) with HOMA-IR ≥ 2.5 presented subclinical insulin resistance with fasting plasma glucose levels and fasting plasma insulin levels in the normal range. Both android fat distribution and insulin resistance correlated to MS in the subgroup of postmenopausal women affected by breast cancer. Conclusions Our results further support the hypothesis that MS, in particular insulin resistance and abdominal fat, can be considered as risk factors for developing breast cancer after menopause. We suggest that HOMA-IR, rather than fasting plasma glucose and fasting plasma insulin levels alone, could be a valuable tool to identify patients with subclinical insulin resistance, which could be relevant for primary prevention and for high risk patient screening.