A Plant-Based Cholesterol-Lowering Diet Score Correlates with Serum LDL-Cholesterol Levels.

BACKGROUND: A cholesterol-lowering diet score was previously developed for epidemiological studies; its association with serum lipid profile was not confirmed yet. METHODS: The score was developed as an adaptation of the dietary portfolio for cholesterol reduction, assigning one point for adherence to seven dietary indicators and ranging from 0 (null adherence) to 7 (highest adherence). The score was calculated for breast cancer patients enrolled in the DEDiCa study using a 7-day food record; serum lipid profile, including total and low-density lipoprotein cholesterol (LDL-C), was evaluated in serum at baseline. RESULTS: Patients with the highest adherence to the cholesterol-lowering diet (i.e., score ≥ 4) reported lower LDL-C level than women with score 0-1 (median: 107 mg/dL and 122 mg/dL, respectively; p < 0.01). The proportion of women with LDL-C above the recommended limit of 116 mg/dL was 60.0% with score 0-1 and 42.6% with score ≥4. Although the score directly correlates with consumption of foods from vegetal sources, it was mildly associated with the healthful plant-based diet index (r-Spearman = 0.51) and the Mediterranean Diet Adherence Screener (r-Spearman = 0.30) Conclusions: These results provide experimental evidence that the cholesterol-lowering diet score is capable of detecting a specific plant-based dietary pattern that affects circulating cholesterol levels.

A novel approach to assess diet diversity: a development of the Nutritional Functional Diversity indicator.

Background and aims: Diversity is a key element of diet quality. The Food Variety Score (FVS) is used to assess diversity, especially in low- and middle-income countries. It sums up the number of foods consumed ignoring their nutrient content. A more suitable index should combine the number of foods consumed and their nutritional composition. We adapted the Nutritional Functional Diversity indicator (NFD), proposed by ecologists, to measure diversity in the human diet. We compared NFD and FVS evaluating subjects' distributions across quartiles of the two diversity indices. To evaluate which one reflected a higher diet quality, we estimated associations between these two diversity indices and diet quality measures, i.e., the Mediterranean Diet Score (MDS) and the Healthy Eating Index-2015 (HEI-2015). Associations were expressed by odds ratios (OR) and corresponding 95% confidence intervals (CI). Materials and methods: We used the data of controls only derived from an integrated series of hospital-based case-control cancer studies conducted in different Italian areas. The NFD identifies groups of foods based on a set of nutrients according to a cluster analysis. Some steps are required: creating a food-nutrient matrix; clustering of the Euclidean food-food distance matrix to identify groups of foods with nutritional (dis)similarities; and calculating the NFD as the ratio between the sum of branch lengths of the dendrogram belonging to the number of foods consumed by individuals (i.e., subject-specific diversity) and the sum of all branch lengths of the dendrogram (i.e., maximal diversity). Results: More than one quarter of individuals (28.4%) were differently classified within quartiles of the two diversity indices. For both indices, increasing the diversity level increased the risk for adhering to MDS (OR for NFD = 11.26; 95% CI: 7.88-16.09, and OR for FVS = 6.80; 95% CI: 4.84-9.54) and to HEI-2015 (OR for NDF = 2.86; 95% CI: 2.39-3.42, and OR for FVS = 2.72; 95% CI: 2.27-3.26). Associations were stronger for NFD. Conclusion: Our findings showed a greater ability of NFD to assess diet quality quantifying the degree of diversity.

Cancers attributable to overweight and obesity in Italy.

BACKGROUND & AIMS: Overweight and obesity are associated with multiple cancers. We quantified the burden of cancer attributable to overweight and obesity in Italy. METHODS: We estimated sex- and cancer site-specific population attributable fractions (PAFs) combining relative risks (from recent meta-analyses) with national obesity prevalence data (from a large sample survey conducted in 2005, to account for a 15-year lag period). Using nationwide mortality statistics and cancer registries data, we estimated the number of cancer cases and deaths attributable to overweight and obesity in Italy in 2020, based on the counterfactual scenario of a body mass index < 25 kg/m2. RESULTS: 3.6% of cancers in men and 4.0% in women in Italy were attributable to overweight and obesity, corresponding, respectively, to over 6900 and 7200 diagnoses in 2020. Attributable deaths were over 3600 in men and 2700 in women. PAFs (attributable cases) of overweight and obesity in men and women were, respectively, 38.1% (215 cases) and 21.8% (49 cases) for esophageal adenocarcinoma, 19.1% (1715 cases) and 14.5% (585 cases) for liver, 18.7% (1692 cases) and 16.7% (747 cases) for kidney, 13.7% (938 cases) and 10.1% (749 cases) for pancreatic, and 10.2% (2389 cases) and 3.4% (690 cases) for colorectal cancers. In women, PAFs were 22.3% (1859 cases) for endometrial and 5.7% (2556 cases) for post-menopausal breast cancer. CONCLUSIONS: The cancer burden associated with overweight and obesity in Italy is considerable, but smaller compared to other high income countries, likely because of the lower prevalence of overweight and obesity in the Italian population.

Cancer mortality associated with low education in Italy.

BACKGROUND: This study provides a nationwide representative quantification of the impact of educational inequalities on cancer mortality in Italy. METHODS: The study is based on prevalence data and mortality rate ratios according to levels of education obtained from the Italian 2011 census cohort, including >35 million individuals aged 30-74. We estimated the population attributable fraction (PAF) and the number of cancer deaths associated with low education (below university degree) in Italy by sex. RESULTS: PAFs for low levels of education were 29.1% among men and 13.3% among women, corresponding to 22,271 cancer deaths associated with low education in men and 7456 in women in 2019. PAFs by cancer site in men were: 53.0% for upper aerodigestive tract (UADT), 44.6% for liver, 41.3% for stomach, 41.3% for lung, 37.0% for bladder, 18.5% for colorectal, 9.8% for prostate and 9.1% for pancreatic cancers. PAFs in women were: 44.5% for cervical, 36.1% for UADT, 34.9% for stomach and 13.9% for colorectal cancers. The cancer sites with the highest number of deaths associated with low education were lung among men (7902/22,271, 35.5%) and colorectum among women (780/7456, 10.5%). CONCLUSIONS: About a quarter of cancer deaths in 2019 in Italy may be prevented by reducing the socioeconomic determinants that contribute to educational disparities in cancer mortality.

Cancers attributable to infectious agents in Italy.

OBJECTIVES: To provide an evidence-based, comprehensive assessment of the current burden of infection-related cancers in Italy. METHODS: We calculated the proportion of cancers attributable to infectious agents (Helicobacter pylori [Hp]; hepatitis B virus [HBV] and hepatitis C virus [HCV]; human papillomavirus [HPV]; human herpesvirus-8 [HHV8]; Epstein-Barr virus [EBV]; and human immunodeficiency virus [HIV]) to estimate the burden of infection-related cancer incidence (2020) and mortality (2017). Data on the prevalence of infections were derived from cross-sectional surveys of the Italian population, and relative risks from meta-analyses and large-scale studies. Attributable fractions were calculated based on the counterfactual scenario of a lack of infection. RESULTS: We estimated that 7.6% of total cancer deaths in 2017 were attributable to infections, with a higher proportion in men (8.1%) than in women (6.9%). The corresponding figures for incident cases were 6.5%, 6.9% and 6.1%. Hp was the first cause of infection-related cancer deaths (3.3% of the total), followed by HCV (1.8%), HIV (1.1%), HBV (0.9%), HPV, EBV and HHV8 (each ≤0.7%). Regarding incidence, 2.4% of the new cancer cases were due to Hp, 1.3% due to HCV, 1.2% due to HIV, 1.0% due to HPV, 0.6% due to HBV and <0.5% due to EBV and HHV8. CONCLUSIONS: Our estimate of 7.6% of cancer deaths and 6.9% of incident cases that were attributable to infections in Italy is higher than those estimated in other developed countries. Hp is the major cause of infection-related cancer in Italy. Prevention, screening and treatment policies are needed to control these cancers, which are largely avoidable.

Adherence to a cholesterol-lowering diet and the risk of prostate cancer.

Evidence suggests a role of serum cholesterol in prostate cancer (PCa) development and of lipid lowering medications in PCa risk reduction. We developed a score for adherence to an established cholesterol-lowering diet and evaluated its association with PCa risk in a multicentric hospital-based case-control study (1294 cases; 1451 matched controls) in Italy (1992-2001). The score was derived from seven dietary indicators which have been reported to lower cholesterol levels: high intake of non-cellulosic polysaccharides (viscous fibres), monounsaturated fatty acids, legumes, seeds/corn oil; low intake of saturated fatty acids, dietary cholesterol, and glycaemic index. Odds ratios (ORs) and corresponding confidence intervals (CIs) were calculated through the unconditional logistic regression model. Although most of the dietary indicators alone were not significantly associated with reduced PCa risk, men who fulfilled 5 to 7 dietary indicators (187 cases and 281 controls) showed a 43% reduction in PCa risk compared to those with 0 to 2 indicators (OR: 0.57; 95% CI: 0.43-0.77). This association was not modified by socio-demographic characteristics or lifestyle factors. In conclusion, adherence to a cholesterol-lowering diet is a favourable factor against the risk of PCa, providing support to dietary guidelines that promote cholesterol reduction through plant-based diets.

Diet Quality as Measured by the Healthy Eating Index 2015 and Oral and Pharyngeal Cancer Risk.

BACKGROUND: Alcohol and tobacco are the major risk factors for oral and pharyngeal cancer, but diet is likely to have a role, too. OBJECTIVE: The objective was to analyze the relationship between adherence to the 2015-2020 Dietary Guidelines for Americans (DGA), as measured by the Healthy Eating Index 2015 (HEI-2015), and oral and pharyngeal cancer risk. Moreover, this work aimed to quantify the number of avoidable cases under different scenarios of increased adherence to the DGA, with the use of the potential impact fraction. This estimates the proportion of cases that would occur if the distribution of the risk factor in the population followed an alternative distribution. DESIGN: A multicenter, case-control study was conducted in Italy between 1991 and 2009. Participants' usual diet for the 2 years preceding study enrolment was assessed using a food frequency questionnaire. PARTICIPANTS AND SETTING: Cases were 946 patients admitted to major hospitals with incident, histologically confirmed oral and pharyngeal cancer. Controls were 2,492 patients admitted to the same hospitals for acute non neoplastic conditions. MAIN OUTCOME MEASURES: The adherence to the DGA was assessed using the HEI-2015 score (range = 0 to 100), based on 13 components. The outcome was oral and pharyngeal cancer. STATISTICAL ANALYSES PERFORMED: Odds ratios and the corresponding 95% CIs were estimated using multiple logistic regression models adjusted for tobacco, alcohol, and other relevant covariates. The potential impact fraction was estimated under different scenarios of adherence to the DGA. RESULTS: In this Italian population the HEI-2015 score ranged from 33.4 to 97.5. A higher HEI-2015 score was associated with a lower risk of oral and pharyngeal cancer, with an odds ratio of 0.70 (95% CI 0.62 to 0.79) for a 10-point increment of the score. The estimated potential impact fraction was 64.8% under the maximum achievable reduction scenario, and it ranged from 9% to 27% following other more feasible scenarios. CONCLUSIONS: The HEI-2015 score was inversely related to oral and pharyngeal cancer risk in this Italian population. This analysis allowed for the estimation of the fraction of preventable cases, under different feasible scenarios. A share of 9% to 27% of avoidable cases of oral and pharyngeal cancer might be obtained across real-world scenarios of adherence to the DGA as measured by the HEI-2015 score.

Caffeinated Coffee Consumption and Health Outcomes in the US Population: A Dose-Response Meta-Analysis and Estimation of Disease Cases and Deaths Avoided.

To explore the role of coffee on health outcomes in the United States, where coffee consumption is common, we conducted a meta-analysis of prospective studies investigating the magnitude (any compared with no consumption) and the dose-response shape (cups per day) of the associations between caffeinated coffee consumption and incidence/mortality of cardiovascular disease (CVD), as well as incidence of type 2 diabetes (T2D), hepatocellular carcinoma (HCC), endometrial cancer, melanoma, and nonmelanoma skin cancer. We selected the desirable health outcomes that have been shown to be positively associated with coffee consumption. Studies were identified by searching PubMed/Embase databases up to September 2019. Inclusion criteria included prospective studies that investigated the relation of ≥3 categories of caffeinated coffee consumption and the outcomes of interest. Twenty-six studies (42 distinct cohorts), with 93,706 cases/deaths and 3,713,932 participants, met the inclusion criteria. In any coffee consumers, there was a significant inverse association with the risk of CVD (RR = 0.90; 95% CI: 0.84, 0.96), T2D (RR = 0.90; 95% CI: 0.85, 0.96), endometrial cancer (RR = 0.85; 95% CI: 0.78, 0.92), melanoma (RR = 0.89; 95% CI: 0.80, 0.99), and nonmelanoma skin cancer (RR = 0.92; 95% CI: 0.89, 0.95). Coffee consumption was also inversely associated with HCC (RR = 0.93; 95% CI: 0.80, 1.08), without reaching statistical significance. The dose-response relation was nonlinear uniquely for CVD (P-nonlinearity = 0.01). In particular, the largest risk reduction was observed for 3-4 cups/d (∼120 mL/cup) and no reduction thereafter. For other outcomes, the risk decreased linearly over the whole coffee consumption range. Current patterns of consumption in the United States would account for a fraction of avoided cases/deaths ranging from 6% to 12% according to the outcome considered. This study confirms the beneficial health effects of caffeinated coffee consumption in the US population on the health outcomes considered, and quantifies their possible magnitude.

Adherence to Mediterranean Diet, Physical Activity and Survival after Prostate Cancer Diagnosis.

Despite the considerable number of studies investigating the Mediterranean diet in prostate cancer (PCa) etiology, very few focused on cancer survival. We assessed the pre-diagnostic diet and physical activity in a cohort of 777 men with PCa diagnosed between 1995 and 2002 in north-eastern Italy; adherence to the Mediterranean diet was evaluated through the Mediterranean Diet Score (MDS). Hazard ratios (HR) of death with confidence intervals (CI) were estimated using the Cox model, adjusting for potential confounders. During 10 years of follow-up, 208 patients (26.8%) died, 75 (9.7%) due to PCa. Patients reporting MDS ≥ 5 showed a higher overall survival than those with MDS < 5 (HR = 0.74; 95% CI: 0.56-0.99). Although high physical activity was not significantly associated with overall survival (HR = 0.79; 95% CI: 0.59-1.07), the HR for all-cause death was the lowest (HR = 0.58; 95% CI: 0.38-0.90) for men reporting MDS ≥ 5 and high physical activity compared to those reporting MDS < 5 and low/moderate physical activity. No association emerged for PCa specific survival. Study findings support the beneficial impact of pre-diagnostic adherence to the Mediterranean diet and physical activity on overall survival; they are mainly driven by risk reduction in non-prostate cancer mortality, which however accounts for about 80% of death in men with PCa.

Adherence to the Mediterranean Diet and Mortality after Breast Cancer.

Adherence to Mediterranean diet has been consistently associated with a reduced mortality in the general population, but evidence for women with breast cancer is scanty. METHODS: A cohort of 1453 women with breast cancer diagnosed between 1991 and 1994 in northern Italy was followed-up for vital status for 15 years after diagnosis. The pre-diagnostic habitual diet was assessed through a structured questionnaire and adherence to the Mediterranean diet was evaluated through the Mediterranean Diet Score. Hazard ratios (HR) of death with confidence intervals (CI) were estimated using Cox model, adjusting for potential confounders. RESULTS: Compared to women who scarcely adhere to the Mediterranean diet (n = 332, 22.8%), those highly adherent (n = 500, 34.4%) reported higher intakes of carbohydrates, mono-unsaturated and poly-unsaturated fatty acids, vitamins, folate, and carotenoids, and lower intakes of cholesterol and animal proteins. Adherence to the Mediterranean diet was associated with a better prognosis: 15-year overall survival of 63.1% for high and 53.6% for low adherence, respectively (p = 0.013). HR for all-cause mortality was 0.72 (95% CI: 0.57-0.92) and HR for breast cancer mortality was 0.65 (95% CI: 0.43-0.98) for women 55 years and older. No significant association emerged for breast cancer mortality in the total cohort. CONCLUSIONS: Although dietary habits may have changed after breast cancer diagnosis, these findings indicate that women who ate according to the Mediterranean dietary pattern prior to their diagnosis may have greater chance of a favorable prognosis after breast cancer diagnosis compared to those who did not.

Association between Nutrient-Based Dietary Patterns and Bladder Cancer in Italy.

Limited knowledge is available on dietary patterns and bladder cancer risk. We analyzed data from an Italian case-control study carried out between 2003 and 2014, including 690 incident bladder cancer cases and 665 hospital-controls. We derived nutrient-based dietary patterns applying principal component factor analysis on 28 selected nutrients. We categorized factor scores according to quartiles, and estimated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) through logistic regression models, adjusted for major confounding factors. We identified four dietary patterns named "Animal products", "Vitamins and fiber", "Starch-rich", and "Animal unsaturated fatty acids". We found an inverse association between the "Vitamins and fiber" pattern and bladder cancer (OR = 0.70, 95% CI: 0.48-0.99, IV versus I quartile category). Inverse relationships of borderline significance were also found for the "Animal products" and the "Animal unsaturated fatty acids" dietary patterns. No significant association was evident for the "Starch-rich" pattern. The current study allowed us to identify major dietary patterns in this Italian population. Our study confirms available evidence and shows that scoring high on a fruit-and-vegetables pattern provides beneficial effects on bladder cancer risk.

Ultrasound assessment of maternal adipose tissue during 1st trimester screening for aneuploidies and risk of developing gestational diabetes.

INTRODUCTION: The objective of the present study is to compare the sonographic measurement of subcutaneous adipose thickness and visceral adipose thickness during 1st trimester screening for aneuploidies between non-diabetic pregnant women and patients who develop 1st trimester or 2nd trimester gestational diabetes mellitus (GDM). MATERIAL AND METHODS: Adipose thickness was measured by transabdominal ultrasound imaging in pregnant women attending our clinic for screening for fetal aneuploidies between 11 and 13 weeks of gestation. During the 1st trimester all patients were evaluated for fasting glycemia in accordance with the International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations. Patients with confirmed fasting glycemia (FPG) ≥92 mg/dL were diagnosed as 1st trimester GDM. Patients with FPG <92 mg/dL underwent a 75-g oral glucose tolerance test between 24 and 28 weeks. RESULTS: The study population included 238 non-diabetic women, 29 women with 1st trimester GDM and 28 women with 2nd trimester GDM. Mean subcutaneous adipose thickness and visceral adipose thickness values in non-diabetic women were 9.8 mm (standard deviation [SD = 4.9) and 7.2 mm (SD = 3.5), respectively. Values in women with 1st trimester GDM were 12.8 mm (SD = 6.5) and 9.9 mm (SD = 4.4). In the 2nd trimester GDM group, the mean subcutaneous adipose thickness was 11.1 mm (SD = 4.6) and the mean visceral adipose thickness 10.5 mm (SD = 5.3). Multiple logistic regression analysis showed that visceral adipose thickness, but not subcutaneous adipose thickness, was significantly and independently associated with both 1st trimester GDM (OR 1.15, 95% CI 1.02-1.29) and 2nd trimester GDM (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.05-1.34). CONCLUSIONS: Sonographic thickness of maternal visceral adipose tissue was greater in women with GDM than in non-diabetic patients, independently of other known risk factors associated with GDM in the 1st and in the 2nd trimester of pregnancy. Thus, this measurement may be considered of clinical use in 1st trimester screening.

Attributable fraction for multiple risk factors: Methods, interpretations, and examples.

The attributable fraction is the candidate tool to quantify individual shares of each risk factor on the disease burden in a population, expressing the proportion of cases ascribable to the risk factors. The original formula ignored the presence of other factors (i.e. multiple risk factors and/or confounders), and several adjusting methods for potential confounders have been proposed. However, crude and adjusted attributable fractions do not sum up to their joint attributable fraction (i.e. the number of cases attributable to all risk factors together) and their sum may exceed one. A different approach consists of partitioning the joint attributable fraction into exposure-specific shares leading to sequential and average attributable fractions. We provide an example using Italian case-control data on oral cavity cancer comparing crude, adjusted, sequential, and average attributable fractions for smoking and alcohol and provide an overview of the available software routines for their estimation. For each method, we give interpretation and discuss shortcomings. Crude and adjusted attributable fractions added up over than one, whereas sequential and average methods added up to the joint attributable fraction = 0.8112 (average attributable fractions for smoking and alcohol were 0.4894 and 0.3218, respectively). The attributable fraction is a well-known epidemiological measure that translates risk factors prevalence and disease occurrence in useful figures for a public health perspective. This work endorses their proper use and interpretation.

Food consumption, meat cooking methods and diet diversity and the risk of bladder cancer.

BACKGROUND: Since food metabolites are eliminated by the urinary tract, several studies have investigated the association between diet and bladder cancer risk. Recently, the World Cancer Research Fund International/American Institute for Cancer Research (WCRF/AICR) suggested a potential beneficial effect of some foods (mainly vegetables, fruit, and milk) in the development of bladder cancer. We investigated the association between food groups and bladder cancer risk, seeking insights into food diversity as well as meat cooking methods. METHODS: Data were derived from an Italian multicentre case-control study, conducted between 2003 and 2014, including 690 bladder cancer cases and 665 frequency-matched controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (95%CIs) for various dietary aspects were estimated by unconditional logistic regression models adjusted for energy intake and the major known risk factors for bladder cancer. RESULTS: Comparing the highest versus the lowest quartiles, consumption of vegetables (OR = 0.62; 95%CI: 0.44-0.88) and milk/yogurt (OR = 0.62; 95%CI: 0.44-0.87) reduced the risk of bladder cancer. Conversely, consumption of meat increased bladder cancer risk with an OR of 1.57 (95%CI: 1.07-2.31), particularly when the meat was stewed (OR = 1.47; 95%CI: 1.03-2.09) or roasted (OR = 1.41; 95%CI: 1.00-1.99). There was a suggestion that a diversified diet reduced the risk of bladder cancer, but this was not significant. CONCLUSIONS: Our study consolidates the role of diet in bladder cancer aetiology, showing a reduced risk for vegetable and milk/yogurt consumption and an increased risk for meat consumption, especially when the meat is stewed or roasted.

Dietary inflammatory index and cancer risk in the elderly: A pooled-analysis of Italian case-control studies.

OBJECTIVES: The aim of this study was to evaluate whether the association between the inflammatory potential of one's diet and cancer risk varies across age groups in a population characterized by widespread use of the Mediterranean diet. METHODS: We analyzed data from a network of case-control studies conducted in Italy between 1991 and 2014. The studies included cancers of the oral cavity (n = 509), pharynx (n = 436), nasopharynx (n = 198), larynx (n = 459), esophagus (n = 304), stomach (n = 230), colon (n = 1225), rectum (n = 728), liver (n = 184), pancreas (n = 326), breast (n = 2569), endometrium (n = 454), ovary (n = 1031), prostate (n = 1294), kidney (n = 767), and bladder (n = 690). Controls were 13 563 patients hospitalized for acute, non-neoplastic conditions. Dietary inflammatory index (DII) scores were computed based on 31 food parameters assessed using a reproducible and validated food frequency questionnaire. Odds ratios were estimated through logistic regression models adjusting for recognized confounding factors. RESULTS: The DII increased with age, with lower scores among men than women, in individuals located in northern rather than in central or southern Italy, and in controls more than in cancer cases. After adjustment for cancer-specific potential confounders, an increasing DII score was directly associated with cancer risk for all considered cancer sites, except for liver and endometrium. Although the DII level varied across age groups, no heterogeneity in cancer risk emerged for any of the considered cancer sites. CONCLUSIONS: In the Italian population, DII scores were higher in elderly than in middle-aged individuals. Although not directly affecting cancer risk, this finding may have important implications for the older population because elevated DII scores, indicating a proinflammatory diet, also have been associated with frailty.

Mediterranean Diet and Bladder Cancer Risk in Italy.

Previous studies have reported that Mediterranean diet is inversely related to the risk of several neoplasms; however, limited epidemiological data are available for bladder cancer. Thus, we examined the association between Mediterranean diet and this neoplasm in an Italian multicentric case-control study consisting of 690 bladder cancer cases and 665 controls. We assessed the adherence to the Mediterranean diet via a Mediterranean Diet Score (MDS), which represents the major characteristics of the Mediterranean diet and ranges from 0 to 9 (from minimal to maximal adherence, respectively). We derived odds ratios (ORs) of bladder cancer according to the MDS score from multiple logistic regression models, allowing for major confounding factors. The ORs of bladder cancer were 0.72 (95% confidence interval, CI, 0.54⁻0.98) for MDS of 4⁻5 and 0.66 (95% CI, 0.47⁻0.93) for MDS of 6⁻9 (p for trend = 0.02) compared to MDS = 0⁻3. Results were similar in strata of sex, age, and education, while the risk appeared somewhat lower in never-smokers and patients with pT1⁻pT4 bladder carcinomas. Among individual components of the MDS, we observed inverse associations for greater consumption of legumes, vegetables, and fish. In our study, which was carried out on an Italian population, the higher adherence to the Mediterranean diet was related to a lower risk of bladder cancer.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations and colorectal cancer risk.

BACKGROUND: The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) released in 2007 eight recommendations for cancer prevention on body fatness, diet and physical activity. Our aim is to evaluate the relation between adherence to these recommendations and colorectal cancer (CRC) risk. METHODS: We pooled data from two Italian case-control studies including overall 2419 patients with CRC and 4723 controls. Adherence to the WCRF/AICR guidelines was summarised through a score incorporating seven of the WCRF/AICR recommendations, with higher scores indicating higher adherence to the guidelines. Odds ratios (ORs) of colorectal cancer were estimated using multiple logistic regression models. RESULTS: Higher adherence to the WCRF/AICR recommendations was associated with a significantly reduced CRC risk (OR 0.67, 95% confidence interval, CI, 0.56-0.80 for a score ≥5 versus <3.5), with a significant trend of decreasing risk for increasing adherence (p < 0.001). Consistent results were found for colon (OR 0.67) and rectal cancer (OR 0.67). Inverse associations were observed with the diet-specific WCRF/AICR score (OR 0.71, 95% CI, 0.61-0.84 for ≥3.5 versus <2.5 points) and with specific recommendations on body fatness (OR 0.82, 95% CI, 0.70-0.97), physical activity (OR 0.86, 95% CI, 0.75-1.00), foods and drinks that promote weight gain (OR 0.70, 95% CI, 0.56-0.89), foods of plant origin (OR 0.56, 95% CI, 0.42-0.76), limiting alcohol (OR 0.87, 95% CI, 0.77-0.99) and salt intake (OR 0.63, 95% CI, 0.48-0.84). CONCLUSION: Our study indicated that adherence to the WCRF/AICR recommendations is inversely related to CRC risk.

Dietary water intake and bladder cancer risk: An Italian case-control study.

Previous studies on the relationship between fluid intake and risk of bladder cancer have generally focused on beverages, and results have been inconsistent. We investigated the relationship between water intake and bladder cancer risk, considering water from both beverages and foods. Between 2003 and 2014 we conducted a multicenter hospital-based case-control study in Italy on 690 cases and 665 frequency-matched controls. Water intake for beverages and foods was computed using the Italian food composition database. Odds ratios (ORs) and the corresponding 95% confidence intervals (95%CIs) for water intake were estimated by unconditional multiple logistic regression models, adjusting for major risk factors for bladder cancer. In the control group, the 64.7% of water intake derived from beverages and 35.4% from foods. Comparing the highest with the lowest quartile of intake, water from beverages (OR=1.14; 95%CI: 0.82-1.59) and water from foods (OR=0.88; 95%CI: 0.61-1.28) were not significantly associated with bladder cancer risk. Some specific water sources showed significant associations with bladder cancer risk (e.g. water from vegetables, OR=0.58; 95%CI: 0.40-0.86). However, these associations may be due to the effect of other components contained in beverages and foods rather than to the water content itself. Considering the intakes of water from both beverages and foods, total water intake was not associated with bladder cancer risk.

Diagnostic value of neutrophil gelatinase-associated lipocalin/matrix metalloproteinase-9 pathway in transitional cell carcinoma of the bladder.

Neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase (MMP)-9, and NGAL/MMP-9 complex have been evaluated as diagnostic markers of several cancers, but results for bladder cancer are scanty. We evaluated these proteins in urine and serum of 89 patients with histologically confirmed bladder cancer and 119 cancer-free controls from a case-control study. Urinary concentrations were standardized on creatinine level. The performance of these proteins as cancer biomarkers was evaluated through the receiver operating characteristic (ROC) analysis. Urinary level of NGAL, MMP-9, and NGAL/MMP-9 complex was higher in current smokers, whereas no impact of dietary habits was observed. After adjusting for tobacco smoking, urinary concentration of MMP-9 was independently associated with cancer invasiveness, grading, and histological subtype, with elevated concentrations among T2-T4 and non-papillary bladder cancers. Conversely, NGAL and NGAL/MMP-9 complex were significantly higher in non-papillary than in papillary subtype. The pattern was less clear in serum, but correlation between urinary and serum concentration was poor, especially for Ta/is-T1 tumors. The ROC analysis confirmed that MMP-9 was the best marker (area under the ROC curve (AUC) = 0.68). Performances were much greater for muscle-invasive bladder cancers (AUC = 0.90), with elevated negative predictive values (97 %). The present study suggests that NGAL/MMP-9 pathway is associated with an aggressive phenotype of bladder cancer. The elevated negative predictive value of MMP-9 and NGAL/MMP-9 complex makes them candidate markers of exclusion test for bladder cancer. These proteins may be integrated in the surveillance of bladder cancer, thus diminishing patients' discomfort and improving compliance.

Combined effect of tobacco smoking and alcohol drinking in the risk of head and neck cancers: a re-analysis of case-control studies using bi-dimensional spline models.

The synergistic effect of tobacco smoking and alcohol consumption on the risk of head and neck cancers has been mainly investigated as a cross-product of categorical exposure, thus leading to loss of information. We propose a bi-dimensional logistic spline model to investigate the interacting dose-response relationship of two continuous exposures (i.e., ethanol intake and tobacco smoking) on the risk of head and neck cancers, representing results through three-dimensional graphs. This model was applied to a pool of hospital-based case-control studies on head and neck cancers conducted in Italy and in the Vaud Swiss Canton between 1982 and 2000, including 1569 cases and 3147 controls. Among never drinkers and for all levels of ethanol intake, the risk of head and neck cancers steeply increased with increasing smoking intensity, starting from 1 cigarette/day. The risk associated to ethanol intake increased with incrementing exposure among smokers, and a threshold effect at approximately 50 g/day emerged among never smokers. Compared to abstainers from both tobacco and alcohol consumption, the combined exposure to ethanol and/or cigarettes led to a steep increase of cancer risk up to a 35-fold higher risk (95 % confidence interval 27.30-43.61) among people consuming 84 g/day of ethanol and 10 cigarettes/day. The highest risk was observed at the highest levels of alcohol and tobacco consumption. Our findings confirmed a combined effect of tobacco smoking and alcohol drinking on head and neck cancers risk, providing evidence that bi-dimensional spline models could be a feasible and flexible method to explore the pattern of risks associated to two interacting continuous-exposure variables.