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Tobacco and alcohol use are the main risk factors for oral and oropharyngeal cancers, yet, dietary habits may also be of importance. Data from a series of case-control studies conducted in 9 countries worldwide (1,670 cases and 1,732 controls) were used to investigate the role of several food groups and body mass index (BMI). Low BMI significantly increased the odds ratio (OR) of cancer more than 2-fold among ever- and never-tobacco users and ever- and never-alcohol drinkers. After adjustment for potential confounders, high intake of fruits and vegetables significantly reduced the OR of cancer compared to low intake among ever-tobacco users (OR 0.4, 95% confidence interval [CI] 0.3-0.6), although not among never-tobacco users (OR 1.1, 95% CI 0.6-2.0). Similarly, the protective effect of high fruit and vegetable consumption was present among ever-drinkers (OR 0.4, 95% CI 0.3-0.6), but not among never-drinkers (OR 1.0, 95% CI 0.6-1.6). In conclusion, low BMI increases the risk of oral cancer, and vegetables and fruits may modulate the carcinogenic effects of tobacco and alcohol.

By providing a broader understanding of the many sustainable benefits of the Mediterranean diet, the Med Diet 4.0 can contribute to the revitalization of the Mediterranean diet by improving its current perception not only as a healthy diet but also a sustainable lifestyle model, with country-specific and culturally appropriate variations. It also takes into account the identity and diversity of food cultures and systems, expressed within the notion of the Mediterranean diet, across the Mediterranean region and in other parts of the world. Further multidisciplinary studies are needed for the assessment of the sustainability of the Mediterranean diet to include these new dimensions.

Sir In a combined analysis of the Nurses' Health Study and the Health Professional Follow-up Study, on a total of 206 women and 143 men with cancer of the pancreas, Schernhammer et al, (2002) did not find an increased risk of pancreatic cancer in relation to history of gallstones or cholecystectomy after adjusting for potential confounding factors. The issue of a possible association between gallstones or cholecystectomy and cancer of the pancreas is, however, still open to discussion, because several investigations reported an excess pancreatic risk in patients with gallstones. Apart from the papers quoted in Schernhammer et al, (2002), some excess risks were found in cohort studies from the United States (Bansal and Sonnenberg, 1996), Denmark (Johansen et al, 1996), and Sweden (Ye et al, 2001), and case–control studies from the United Kingdom (Cuzick and Babiker, 1989), Greece (Kalapothaki et al, 1993), and Israel (Schattner et al, 1997). The strength of the association, however, was variable across studies, and different potential confounding factors were not always taken into account. In order to provide further information on the issue, we updated the analysis of a case–control study conducted in Italy between 1983 and 1992 (La Vecchia et al, 1990). Briefly, the study included 362 patients from the major teaching and general hospitals in Greater Milan with incident, histologically confirmed pancreatic cancer (229 men, 133 women, median age 59 years), and 1552 controls (1141 men, 411 women, median age 55 years) admitted to the same network of hospitals for acute, non-neoplastic conditions, unrelated to alcohol or tobacco consumption (33% traumas, 17% nontraumatic orthopedic conditions, 36% acute surgical diseases, and 14% other miscellaneous disorders). Less than 3% of cases and controls approached refused the interview. Trained interviewers identified and questioned cases and controls using a structured questionnaire, including information on education and other socioeconomic factors, anthropometric measures, general lifestyle habits, such as tobacco and alcohol consumption, and a few selected indicator foods. The patients were also asked if they had a diagnosis of selected medical conditions, and the age at first diagnosis was recorded. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models, including terms for age, education, tobacco consumption, body mass index, and history of diabetes. Table 1 gives the distribution of pancreatic cancer cases and controls, and the corresponding ORs, according to history of cholelithiasis. Subjects with a history of cholelithiasis showed no increased risk of cancer of the pancreas (OR=1.03, 95% CI=0.67–1.59). The OR was 1.33 (95% CI=0.74–2.40) for subjects with a diagnosis of cholelithiasis less than 10 years before interview, and 0.80 (95% CI=0.43–1.50) for diagnosis 10 or more years before. Table 1 Relation between pancreatic cancer and history of cholelithiasis among 362 cases and 1552 controls (Milan, Italy, 1983–1992) Thus, our findings are consistent with those of the Nurses' Health Study and the Health Professional Follow-up Studies (Schernhammer et al, 2002), and indicate that cholelithiasis is not materially associated with pancreatic cancer risk after major identified confounding factors have been considered. A modestly increased risk was observed 10 years after a diagnosis of cholelithiasis, but no greater excess risk can be found 10 or more years after. Thus, if any association exists, it is unlikely to be causal. The apparent association reported from several case–control studies can at least in part be because of a more accurate recall of gallbladder disease by pancreatic cancer patients. In our study, however, information on medical history proved satisfactorily reproducible (Bosetti et al, 2001), indicating that recall bias is unlikely to have played a major role. Other potential biases of this study should be limited, given the almost complete response rate, the administration of a standard questionnaire under similar conditions, and the same catchment area for cases and controls.

e11571 Background: The evidence supporting the use of trastuzumab (T) in metastatic setting comes from studies that included (almost) only patients who never received prior T. We investigated the effectiveness of T as first line therapy for metastatic breast cancer (mBC) in women already treated with T in the adjuvant setting. Methods: Using record linkage of 4 admistrative healthcare databases of Lombardy, Italy, we identified 2046 women treated with T for early BC in 2006-2009, 96 of whom developed a metastasis and were retreated with T in first line for mBC (treatment group). We compared overall survival (OS) of these women with that of 197 women treated with T in first line for mBC, who were treated with therapies other than T for early disease (control group). We computed Kaplan-Meier 2-year OS, and used a proportional hazard model to estimate the hazard ratio (HR) of death of the intervention group as compared to the control group. Results: Two-year OS was 60.0% in the treatment group and 59.5% in the control group. The HR of death of the treatment group compared to the control group, adjusted by age and metastatic site, was 0.80 (95% Confidence Interval 0.50-1.28). Conclusions: Given the unavailability of data from randomized clinical trials, our data provide suggestive evidence that the outcome of women receiving first line T treatment for mBC after T-failure in adjuvant setting is comparable to that of women not exposed to T for early BC.

We applied digital spatial profiling for 87 immune and stromal genes to lymph node germinal center (GC) dark- and light-zone (DZ/LZ) regions of interest to obtain a differential signature of these two distinct microenvironments. The spatially resolved 53-genes signature, comprising key genes of the DZ mutational machinery and LZ immune and mesenchymal milieu, was applied to the transcriptomes of 543 GC-related diffuse large B cell lymphomas and double-hit (DH) lymphomas. According to the DZ/LZ signature, the GC-related lymphomas were sub-classified into two clusters. The subgroups differed in the distribution of DH cases and survival, with most DH displaying a distinct DZ-like profile. The clustering analysis was also performed using a 25-genes signature composed of genes positively enriched in the non-B, stromal sub-compartments, for the first time achieving DZ/LZ discrimination based on stromal/immune features. The report offers new insight into the GC microenvironment, hinting at a DZ microenvironment of origin in DH lymphomas.

Diet and inflammation have been suggested to be important risk factors for colorectal cancer (CRC). In the present study, we examined the association between the dietary inflammatory index (DII) and the risk of CRC in a multi-centre case-control study conducted between 1992 and 1996 in Italy. The study included 1225 incident colon cancer cases, 728 incident rectal cancer cases and 4154 controls hospitalised for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed using a validated seventy-eight-item FFQ that included assessment of alcohol intake. Logistic regression models were used to estimate the OR adjusted for age, sex, study centre, education, BMI, alcohol drinking, physical activity and family history of CRC. Energy intake was adjusted using the residual method. Subjects with higher DII scores (i.e. with a more pro-inflammatory diet) had a higher risk of CRC, with the DII being used both as a continuous variable (OR(continuous) 1.13, 95 % CI 1.09, 1.18) and as a categorical variable (OR(quintile 5 v. 1) 1.55, 95 % CI 1.29, 1.85; P for trend < 0.0001). Similar results were observed when the analyses were carried out separately for colon and rectal cancer cases. These results indicate that a pro-inflammatory diet is associated with an increased risk of CRC.

Cells were cultured for up to 5 d with anti-CD40 antibody (α-CD40) or without stimulation (w/o). (A) Percentages of living cells (Topro negative) were determined daily by flow cytometry. The bars show mean percentages of living cells of three independent experiments. Error bars show the SD. (B) Numbers of viable cells were determined daily by trypan blue staining and cell counting. The bars show mean cell counts of three independent experiments. Error bars show the SD. (C) Splenic B cells of LMP1/CD40 and control mice were labeled with CFSE and cultured with α-CD40, IL-4, α-CD40 plus IL-4, LPS, or without stimulation (w/o). After 5 d of culture, the proliferation rate of B220 B cells was determined by flow cytometric analysis of the CFSE staining. Percentages of divided cells ± the SD of three individual experiments are indicated.<b>Copyright information:</b>Taken from "Constitutive CD40 signaling in B cells selectively activates the noncanonical NF-κB pathway and promotes lymphomagenesis"The Journal of Experimental Medicine 2008;205(6):1317-1329.Published online 9 Jun 2008PMCID:PMC2413030.

On the basis of individual-level data we confirm and further update to 2014 the decreasing trend in alcohol consumption in Italy over the last few decades, mainly due to the fall in wine consumption. This may be due to anti-alcohol policies, programs and campaigns adopted and developed over the last decade. It also reflects socio-cultural changes in drinking, particularly in younger generations.

This Italian study confirms a favourable role of MD on colorectal cancer risk.