Family history of cancer and the risk of cancer: a network of case-control studies

Background The risk of many cancers is higher in subjects with a family history (FH) of cancer at a concordant site. However, few studies investigated FH of cancer at discordant sites. Patients and methods This study is based on a network of Italian and Swiss case-control studies on 13 cancer sites conducted between 1991 and 2009, and including more than 12 000 cases and 11 000 controls. We collected information on history of any cancer in first degree relatives, and age at diagnosis. Odds ratios (ORs) for FH were calculated by multiple logistic regression models, adjusted for major confounding factors. Results All sites showed an excess risk in relation to FH of cancer at the same site. Increased risks were also found for oral and pharyngeal cancer and FH of laryngeal cancer (OR = 3.3), esophageal cancer and FH of oral and pharyngeal cancer (OR = 4.1), breast cancer and FH of colorectal cancer (OR = 1.5) and of hemolymphopoietic cancers (OR = 1.7), ovarian cancer and FH of breast cancer (OR = 2.3), and prostate cancer and FH of bladder cancer (OR = 3.4). For most cancer sites, the association with FH was stronger when the proband was affected at age <60 years. Conclusions Our results point to several potential cancer syndromes that appear among close relatives and may indicate the presence of genetic factors influencing multiple cancer site

Proanthocyanidins and other flavonoids in relation to endometrial cancer risk: a case–control study in Italy

Background: Because of their antioxidant and antimutagenic properties, flavonoids may reduce cancer risk. Some flavonoids have antiestrogenic effects that can inhibit the growth and proliferation of endometrial cancer cells. Methods: In order to examine the relation between dietary flavonoids and endometrial cancer, we analysed data from an Italian case–control study including 454 incident, histologically confirmed endometrial cancers and 908 hospital-based controls. Information was collected through a validated food-frequency questionnaire. We applied data on food and beverage composition to estimate the intake of flavanols, flavanones, flavonols, anthocyanidins, flavones, isoflavones, and proanthocyanidins. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multiple logistic regression models conditioned on age and study centre and adjusted for major confounding factors. Results: Women in the highest quartile category of proanthocyanidins with ⩾3 mers vs the first three quartile categories had an OR for endometrial cancer of 0.66 (95% CI=0.48–0.89). For no other class of flavonoids, a significant overall association was found. There was a suggestion of an inverse association for flavanones and isoflavones among women with body mass index <25 kg m−2, and, for flavanones, among parous or non-users of hormone-replacement therapy women. Conclusion: High consumption of selected proanthocyanidins may reduce endometrial cancer risk

Nutrient dietary patterns and the risk of laryngeal cancer : an Italian case-control study

Introduction. Several studies have indicated a role of diet in the etiology of laryngeal cancer. Since foods and nutrients tend to be closely related and act synergistically, the pecific effect of each dietary component of interest may be difficult to identify and can be partly confounded by other dietary components. Dietary patterns have thus been proposed as a practical tool to describe the association between diet and cancer, given their ability to capture the variations in overall food intake (Newby, Tucker 2004). A few studies have investigated the role of diet on laryngeal cancer through factor analysis. Aims We applied exploratory principal component factor analysis (PCFA) to identify a posteriori dietary patterns for a multicentric case-control study conducted in Italy on cancer of the larynx. This a posteriori technique allows to integrate several dietary exposures (i.e. foods, food groups, nutrients) into a smaller number of dietary patterns, that are independent from one another and can be evaluated as risk factors in subsequent analysis for the assessment of cancer risk. Methods A case-control study of cancer of the larynx was conducted from 1992 and 2000 in the provinces of Milan and Pordenone, in the Northern Italy. Cases were 460 subjects (415 men, 45 women) admitted to major teaching and general hospitals in the study areas with incident, histologically confirmed squamous cell cancer of the larynx, diagnosed no longer than 1 year before the interview. Controls were 1088 subjects (863 men, 225 women) admitted to the same hospitals for a wide spectrum of acute, non-neoplastic conditions, unrelated to smoking or alcohol drinking, or long term modifications of diet. The subjects\u2019 diet was assessed using a valid and reproducible food frequency questionnaire (FFQ) including 78 foods and beverages, as well as a range of the most common Italian recipes. Subjects were asked to indicate the average weekly consumption for each dietary item; intakes lower than once a month were coded as 0.5 per week. To estimate the intake of various nutrients, an Italian food composition database was used. We performed an exploratory PCFA on a selected set of 28 major macro- and micro-nutrients. We preliminarily evaluated the correlation matrix to determine if it was factourable, trough visual inspection and statistical procedure (Bartlett\u2019s test of sphericity). Moreover, we evaluated the Kaiser-Meyer-Olkin measure and individual measures of sampling adequacy (Kaiser, 1974). We chose the number of factors to retain based on the following criteria: factor eigenvalue greater than 1, scree plot examination and factor interpretability. We applied a varimax rotation to the factor loadings matrix to achieve a simpler and more interpretable solution. We used nutrients with rotated factor loading greater or equal to 0.63 on a given factor to name the pattern. Factor scores were defined for each subject and for each factor following the weighted least square method. They indicate the degree to which each subject\u2019s diet conforms to one of the identified patterns. To examine the robustness of the identified dietary patterns, we performed a principal axis factor analysis on the standardized nutrients and a maximum likelihood factor analysis after logarithmic transformation of the original nutrients. We calculated factor scores referring to the multiple regression method and standardizing the results. The correlations between scores referring to the same factor calculated with different methods were equal to 1 for all the comparisons. We also performed factor analysis separately within male and female subsamples and within different centers. All these checks yielded dietary patterns consistent with PCFA the ones obtained on the overall sample. To assess the reliability and refine the identified factors, we evaluated the internal consistency of those nutrients with a loading greater than 0.40 using standardized Cronbach\u2019s coefficient alpha. We calculated coefficient alphas for each factor and coefficient alphas when item deleted (Cronbach, 1951). To confirm the internal reproducibility of the identified patterns, individuals were randomly placed into one of two equally sized groups, and PCFA was performed separately in both subsamples. For each factor, we grouped participants into three categories according to quintiles of factor scores among the control population, and estimated the odds ratio and corresponding 95% confidence intervals using unconditional multiple logistic regression models, including all the factors simultaneously. The model was adjusted for sex, age, study center, education, body mass index, physical activity, tobacco smoking, and alcohol drinking. Results Five factors were retained according to the defined criteria. These factors explained 79% of the total variance of the original nutrients. The first pattern, named Animal products, had the greatest loadings on calcium, phosphorus, riboflavin, animal protein, saturated fatty acids, zinc, and cholesterol. The second pattern, named Starch-rich, had the greatest loadings on starch, vegetable protein, and sodium. The third pattern, named Vitamins and fiber, had the greatest loadings on vitamin C, total fiber, beta-carotene equivalents, and total folate. The fourth pattern, named Seed oils, had the greatest loadings on linoleic acid, vitamin E, and linolenic acid. The fifth pattern, named Fish-rich, had the greatest loadings on other polyunsaturated fatty acids, and vitamin D. A direct association was observed between the Animal products pattern and laryngeal cancer (OR=1.94, 95% CI: 1.39-2.70). A borderline direct association was observed between the Starch-rich pattern and laryngeal cancer (OR=1.30, 95% CI: 0.93-1.81). An inverse relationship was observed between the Vitamins and fiber pattern and laryngeal cancer (OR=0.56, 95% CI: 0.41-0.76). No relationship was evident between the Seed oils pattern and laryngeal cancer (OR=0.98, 95% CI: 0.70-1.37). A direct association was found between the Fish-rich pattern and the laryngeal cancer (OR=2.09, 95% CI: 1.51-2.90). Conclusions The role of dietary habits on the risk of laryngeal cancer was evaluated through exploratory PCFA on 28 major nutrients of interest. We identified 5 major dietary patterns, explaining about 80% of the total variance of the original nutrients. Our results indicated that the Animal products and Fish-rich patterns are potentially unfavourable indicators of risk for laryngeal cancer, while the Vitamins and fiber pattern is inversely related to laryngeal cancer

Are Major a Posteriori Dietary Patterns Reproducible in the Italian Population? A Systematic Review and Quantitative Assessment

Although a posteriori dietary patterns (DPs) naturally reflect actual dietary behavior in a population, their specificity limits generalizability. Among other issues, the absence of a standardized approach to analysis have further hindered discovery of genuinely reproducible DPs across studies from the same/similar populations. A systematic review on a posteriori DPs from principal component analysis or exploratory factor analysis (EFA) across study populations from Italy provides the basis to explore assessment and drivers of DP reproducibility in a case study of epidemiological interest. First to our knowledge, we carried out a qualitative (i.e., similarity plots built on text descriptions) and quantitative (i.e., congruence coefficients, CCs) assessment of DP reproducibility. The 52 selected articles were published in 2001–2022 and represented dietary habits in 1965–2022 from 70% of the Italian regions; children/adolescents, pregnancy/breastfeeding women, and elderly were considered in 15 articles. The included studies mainly derived EFA-based DPs on food groups from food frequency questionnaires and were of “good quality” according to standard scales. Based on text descriptions, the 186 identified DPs were collapsed into 113 (69 food-based and 44 nutrient-based) apparently different DPs (39.3% reduction), later summarized along with the 3 “Mmixed-Salad/Vegetable-based Patterns,” “Pasta-and-Meat-oriented/Starchy Patterns,” and “Ddairy Products” and “Ssweets/Animal-based Patterns” groups, by matching similar food-based and nutrient-based groups of collapsed DPs. Based on CCs (215 CCs, 68 DPs, 18 articles using the same input lists), all pairs of DPs showing the same/similar names were at least “fairly similar” and ∼81% were “equivalent.” The 30 “equivalent” DPs ended up into 6 genuinely different DPs (80% reduction) that targeted fruits and (raw) vegetables, pasta and meat combined, and cheese and deli meats. Such reduction reflects the same study design, list of input variables, and DP identification method followed across articles from the same groups. This review was registered at PROSPERO as CRD42022341037

Selected micronutrient intake and the risk of colorectal cancer.

The relationship between estimated intake of selected micronutrients and the risk of colorectal cancer was analysed using data from a case-control study conducted in northern Italy. The study was based on 828 patients with colon cancer, 498 with rectal cancer and 2,024 controls in hospital for acute, non-neoplastic, non-digestive tract diseases. Relative risks (RRs) of intake quintiles were computed after allowance for age, sex and other major potential confounding factors, including an estimate of total energy intake. No apparent trend in risk across intake quintiles was evident for retinol, vitamin D, methionine and calcium. For beta-carotene, ascorbic acid, vitamin E and folate there was a trend of a protective effect with increasing consumption: the RR for the highest versus the lowest quintile was 0.32 for beta-carotene, 0.40 for ascorbic acid, 0.60 for vitamin E and 0.52 for folate. These inverse associations were similar for colon and rectal cancer, and consistent across strata of sex and age. When simultaneous allowance was made for all these micronutrients, besides other covariates, the only persistent protective effects were for beta-carotene (RR = 0.38 for the highest quintile) and ascorbic acid (RR = 0.52). Whether this reflects a specific, or stronger, effect of these micronutrients, rather than problems of collinearity between micronutrients or other limitations of the data, remains open to discussion. Still, this study suggests that specific micronutrients may exert an independent protective effect against colorectal carcinogenesis

Dietary Patterns in Italy and the Risk of Renal Cell Carcinoma

Background: Conclusive evidence on foods, nutrients, or dietary patterns and the risk of renal cell carcinoma (RCC) is lacking in the literature. Methods: We considered data from an Italian hospital-based case\u2013control study (1992\u20132004) on 767 incident RCC cases and 1534 controls. A posteriori dietary patterns were identified by applying principal component factor analysis on 28 nutrients derived from a 78-item food-frequency questionnaire. We estimated the odds ratios (ORs) of RCC and corresponding 95% confidence intervals (CIs) for each quartile category (compared to the lowest one) using conditional multiple logistic regression models providing adjustment for major confounding factors. Results: We identified four dietary patterns, named \u201cAnimal products\u201d, \u201cStarch-rich\u201d, \u201cVitamins and fiber\u201d, and \u201cCooking oils and dressings\u201d. Higher intakes of the \u201cStarch-rich\u201d pattern were positively associated with RCC risk (OR = 1.38, 95% CI: 1.04\u20131.82 for the highest quartile, p = 0.018). The association was inverse with the \u201cCooking oils and dressings\u201d pattern (OR = 0.61, 95% CI: 0.47\u20130.80, p &lt; 0.001), whereas no association was found with \u201cAnimal products\u201d and \u201cVitamins and fiber\u201d patterns. Conclusions: Higher intakes of starch-related foods may increase RCC risk, whereas consumption of olive and seed oils may favorably influence RCC risk

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