A systematic review on maternal and perinatal factors influencing breast development.

BACKGROUND: A secular trend towards earlier age at menarche has been reported, but the trend in breast development is less clear. We reviewed the evidence on the relationship between in utero and early life events and breast onset/development. METHODS: Eligible studies were identified in PubMed and Embase databases. We selected studies in which female human exposure during fetal or the first years of life was measured or estimated, and associations with breast onset or development were evaluated. RESULTS: Of the 49 cohort studies and 5 cross-sectional studies identified, 43 provided sufficient data to assess associations. High maternal weight, primiparity, and early weight gain, were related to an increased risk of early breast onset/development in most of the studies that analysed these associations, whereas late breast onset/development was associated with preterm birth. Results were inconsistent for smoking in pregnancy, maternal hypertensive disorders, breastfeeding, diabetes, and small for gestational age. No association emerged for maternal age at delivery, alcohol drinking, and selected drug use during pregnancy, and low birth weight. CONCLUSIONS: The results of this review show that high maternal weight, primiparity and early weight gain were associated with an increased risk of early breast onset/development. Late breast onset/development was associated with preterm birth. Breast development is a key physical marker of puberty onset, and early puberty development is linked to consequences that can reverberate throughout life. Answering the questions about the interconnections between pre/postnatal environmental exposures and their impact on puberty, represents an important area of multidisciplinary research.

Trend of change of sperm count and concentration over the last two decades: A systematic review and meta-regression analysis.

BACKGROUND: Since the 1970s, several studies found that sperm concentration (SC) and total sperm count (TSC) constantly worsened over time, mainly in high-income countries. OBJECTIVES: To evaluate whether the decreasing trend in sperm count is continuing in Western European countries and USA, we performed a systematic review and meta-regression analysis. MATERIALS AND METHODS: Embase and Pubmed/Medline were searched papers published in English in the 2000-2020 period limiting the search to data collected in the USA and Western European countries. RESULTS: We identified 62 articles and pooled information on 24,196 men (range 10-2,523), collected from 1993 to 2018. Considering all the studies, random-effects meta-regression analyses showed no significant trend for SC (slope per year -0.07 mil/mL, p-value = 0.86). Negative trends of SC were detected in Scandinavian countries (slope per year -1.11 mil/mL, 95% CI: -2.40 to +0.19; p-value = 0.09), but the findings were statistically not significant. No significant trends of SC were detected in Central Europe (slope per year +0.23, 95% CI -2.51 to +2.96; p-value = 0.87), the USA (slope per year +1.08, 95% CI -0.42 to +2.57; p-value = 0.16), and Southern Europe (slope per year +0.19, 95% CI -0.99 to +1.37; p-value = 0.75). We have analyzed separately findings from studies including sperm donors, fertile men, young unselected men (unselected men, study mean age < 25 years) and unselected men (unselected men, study mean age ≥ 25 years). No significant trends of SC were observed among sperm donors (slope per year -2.80, 95% CI -6.76 to +1.17; p-value 0.16), unselected men (slope per year -0.23, 95% CI -1.58 to +1.12; p-value 0.73), young unselected men (slope per year -0.49, 95% CI -1.76 to +0.79; p-value 0.45), fertile men (slope per year +0.29, 95% CI -1.09 to +1.67; p-value 0.68). DISCUSSION AND CONCLUSION: The results of this analysis show no significant trends in SC, in USA, and selected Western European countries.

Cancer mortality and predictions for 2022 in selected Australasian countries, Russia, and Ukraine with a focus on colorectal cancer.

OBJECTIVE: We aimed at predicting cancer mortality rates for the current year for the Russian Federation, Ukraine, Israel, Hong Kong SAR, Japan, Korea, and Australia, with a focus on colorectal cancer. METHODS: We retrieved official death certification and population data from the WHO and the United Nations Population Division databases. We analyzed mortality for all cancers combined and for 10 major cancer sites from 1970 to 2019, or the latest available year. We predicted numbers of deaths and age-standardized mortality rates for 2022 using Poisson joinpoint regression models. We estimated the number of averted deaths over the period 1994-2022 because of the decline in mortality rates. RESULTS: Total cancer mortality declined in all countries and both sexes. Russia had the highest total cancer predicted rates for 2022: 156.4/100 000 (world standard) in men and 81.4 in women; the lowest rates were reported in Israeli men (90.6/100 000) and Korean women (44.5/100 000). Between 1994 and 2022, a total of 1 487 000 deaths were estimated to be avoided in Russia, 502 000 in Ukraine, 58 000 in Israel, 102 000 in Hong Kong SAR, 1 020 000 in Japan, 533 000 in the Republic of Korea, and 263 000 in Australia. Colorectal cancer mortality trends were downward for the last decades with favorable predictions for 2022 in both sexes. CONCLUSION: In the countries considered, predicted downward trends started later and were less marked than those in the European Union and the USA. Despite overall favorable predictions, colorectal cancer remains one of the major causes of cancer mortality.

Prevalence of polycystic ovary syndrome in European countries and USA: A systematic review and meta-analysis.

We conducted a systematic review and meta-analyses of the prevalence of Polycystic Ovary Syndrome (PCOS) and the frequency of its phenotypes in Europe and the USA, also focusing on temporal trends of the condition, to compare the PCOS prevalence among populations with a similar level of diagnostic resources availability and attitudes toward health problems, to improve comparability of estimates. We considered Europe and USA, two high-income areas with these characteristics. The overall PCOS prevalence according to the NIH1990, ESHRE/ASRM 2003, AES-PCOS diagnostic criteria was respectively 6.2 % (95%CI 5.3-7.0), 19.5 % (95%CI 17.3-21.6), and 15.0 % (95%CI 12.9-17.1), with no appreciable heterogeneity across geographic areas. Phenotype A, the "complete PCOS", showed higher prevalence in all areas (44.8%, 95%CI 40.3-49.3), followed by phenotype D, called "non-hyperandrogenic PCOS" (19.5%), phenotype C termed as "ovulatory PCOS" (16.2%), and phenotype B, presenting as phenotype A but without polycystic ovarian morphology (14.9%). In all the studies analysing temporal trends of PCOS, an increase in prevalence of PCOS was reported, due, at least in part, to changing diagnostic criteria. The prevalence of PCOS is similar in European countries and the USA. Interestingly, some differences in the frequency of PCOS phenotypes emerged between the two areas with a higher frequency of phenotype A and a lower one of phenotype C in the USA. Recognizing the factors which explain these differences would lead to a better understanding of the etiopathogenesis and the clinical expression of PCOS.

Peptic ulcer as mediator of the association between risk of gastric cancer and socioeconomic status, tobacco smoking, alcohol drinking and salt intake.

BACKGROUND: Peptic ulcer disease (PUD) and gastric cancer (GC) are more prevalent in individuals with low socioeconomic status (SES) and share several risk factors. The aim of this study was to investigate the mediating role of PUD in the association between established risk factors and GC. METHODS: We conducted a pooled analysis of 12 studies from the Stomach Cancer Pooling Project Consortium, including a total of 4877 GC cases and 11 808 controls. We explored the mediating role of PUD in the association between SES, tobacco smoking, heavy alcohol drinking and salt intake, and GC. Also, we assessed the ORs and 95% CIs of the risk factors and both PUD and GC. RESULTS: PUD mediated 36% of the smoking effect mainly among men. Other risk factors were only slightly mediated by PUD (SES, 5.3%; heavy alcohol drinking, 3.3%; and salt intake, 2.5%). No significant difference was found when excluding PUD diagnosed within 2 years from GC. CONCLUSIONS: Our study provides innovative information on the mechanism of stomach mucosal damage leading to PUD and GC, with respect to the effect of tobacco smoking in particular.

Chronic obstructive pulmonary disease (COPD) mortality trends worldwide: An update to 2019.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) incidence, prevalence, mortality and socioeconomic burden are considerable and vary across countries. The aim of the present study was to update the analysis of COPD mortality worldwide using data from the World Health Organization (WHO) up to 2019. METHODS: We obtained COPD mortality and population data for 22 European countries and the European Union (EU) as a whole, 10 American countries and six other countries from the WHO mortality database. We calculated age-standardized mortality rates in both sexes and examined trends by country with joinpoint analysis between 1994 and 2019. RESULTS: Between 2005-2007 and 2015-2017, overall COPD mortality decreased in EU men (-16.3%) but increased in women (12.7%) to reach rates of 14.0/100,000 in men and of 6.4/100,000 in women. In the United States, mortality declined in men to 21.3/100,000 but rose in women to 18.3/100,000. Mortality declined in most Latin American countries and all Asian countries, while an increase in Australian women was observed. CONCLUSION: A steady decrease in COPD mortality was observed in most of countries for men, whilst a different trend was observed in women in several countries. These trends are largely explained by changes in smoking habits, with an additional contribution of air pollution and occupational exposures. Despite past and ongoing tobacco control initiatives, this condition still remains a leading cause of death, in particular in countries with lower socio-demographic indices.

Comorbidity patterns, family history and breast cancer risk: a latent class analysis.

BACKGROUND: Limited evidence exists on how the presence of multiple conditions affects breast cancer (BC) risk. METHODS: We used data from a network hospital-based case-control study conducted in Italy and Switzerland, including 3034 BC cases and 3392 controls. Comorbidity patterns were identified using latent class analysis on a set of specific health conditions/diseases. A multiple logistic regression model was used to derive ORs and the corresponding 95% CIs for BC according to the patterns, adjusting for several covariates. A second model was fitted including an additional effect of FH on the comorbidity patterns. RESULTS: With respect to the 'healthy' pattern, the 'metabolic disorders' one reported an OR of 1.23 (95% CI 1.02 to 1.49) and the 'breast diseases' an OR of 1.86 (95% CI 1.23 to 2.83). The remaining two patterns reported an inverse association with BC, with ORs of 0.77, significant only for the 'hysterectomy, uterine fibroids and bilateral ovariectomy'. In the second model, FH was associated with an increased risk of the 'breast diseases' pattern (OR=4.09, 95% CI 2.48 to 6.74). Non-significant increased risk of the other patterns according to FH emerged. CONCLUSION: We identified mutually exclusive patterns of comorbidity, confirming the unfavourable role of those related to metabolic and breast disorders on the risk of BC, and the protective effect of those related to common surgical procedures. FH reported an incremented risk of all the comorbidity patterns. IMPACT: Identifying clusters of comorbidity in patients with BC may help understand their effects and enable clinicians and policymakers to better organise patient and healthcare management.

Inverse Association between Dietary Iron Intake and Gastric Cancer: A Pooled Analysis of Case-Control Studies of the Stop Consortium.

Background: Inconsistent findings have been reported regarding the relationship between dietary iron intake and the risk of gastric cancer (GC). Methods: We pooled data from 11 case-control studies from the Stomach Cancer Pooling (StoP) Project. Total dietary iron intake was derived from food frequency questionnaires combined with national nutritional tables. We derived the odds ratios (ORs) and 95% confidence intervals (CIs) for quartiles of dietary iron through multivariable unconditional logistic regression models. Secondary analyses stratified by sex, smoking status, caloric intake, anatomical subsite and histological type were performed. Results: Among 4658 cases and 12247 controls, dietary iron intake was inversely associated with GC (per quartile OR 0.88; 95% CI: 0.83-0.93). Results were similar between cardia (OR = 0.85, 95% CI = 0.77-0.94) and non-cardia GC (OR = 0.87, 95% CI = 0.81-0.94), and for diffuse (OR = 0.79, 95% CI = 0.69-0.89) and intestinal type (OR = 0.88, 95% CI = 0.79-0.98). Iron intake exerted an independent effect from that of smoking and salt intake. Additional adjustment by meat and fruit/vegetable intake did not alter the results. Conclusions: Dietary iron is inversely related to GC, with no difference by subsite or histological type. While the results should be interpreted with caution, they provide evidence against a direct effect of iron in gastric carcinogenesis.

Trends in Dizygotic and Monozygotic Spontaneous Twin Births During the Period 2007-2017 in Lombardy, Northern Italy: A Population-Based Study.

In this study, we analyzed the estimated frequency of monozygotic (MZ) and dizygotic (DZ) spontaneous twins in Lombardy during the period 2007-2017. This is a population-based study using the regional healthcare utilization databases of the Lombardy Region. The total number of spontaneous twin deliveries, in separate strata of like and unlike sex, was obtained. Moreover, estimates of DZ and MZ twin births were calculated using Weinberg's method. The standardized rates (SRs), adjusted for maternal age, of DZ and MZ twin births were computed according to calendar period. The twinning rates were calculated among strata of parity and maternal age. Finally, DZ:MZ ratio was calculated. Among the 734,278 spontaneous deliveries, 9176 (12.5 out of 1000 births) couples of twins were identified. In the three periods considered (i.e. 2007-2010, 2011-2014 and 2015-2017), no trend in the SRs of MZ twins was observed, respectively 0.41 (95% CI [0.40, 0.43]), 0.43 (95% CI [0.42, 0.45]) and 0.43 (95% CI[0.42, 0.45]). Differently, a slightly decreasing trend was observed in DZ twins SRs, respectively 0.87 (95% CI [0.84, 0.89]), 0.81 (95% CI [0.79, 0.83]), and 0.78 (95% CI [0.76, 0.80]). As concerns parity and maternal age, the rate of DZ twin births was consistently higher in nulliparae women aged 35 years or more. In our cohort, despite the increase of maternal age, a decline of spontaneous twin births emerged, especially due to the downward trend of DZ twins.

The mediating role of combined lifestyle factors on the relationship between education and gastric cancer in the Stomach cancer Pooling (StoP) Project.

BACKGROUND: The causal pathway between high education and reduced risk of gastric cancer (GC) has not been explained. The study aimed at evaluating the mediating role of lifestyle factors on the relationship between education and GC METHODS: Ten studies with complete data on education and five lifestyle factors (smoking, alcohol drinking, fruit and vegetable intake, processed meat intake and salt consumption) were selected from a consortium of studies on GC including 4349 GC cases and 8441 controls. We created an a priori score based on the five lifestyle factors, and we carried out a counterfactual-based mediation analysis to decompose the total effect of education on GC into natural direct effect and natural indirect effect mediated by the combined lifestyle factors. Effects were expressed as odds ratios (ORs) with a low level of education as the reference category. RESULTS: The natural direct and indirect effects of high versus low education were 0.69 (95% CI: 0.62-0.77) and 0.96 (95% CI: 0.95-0.97), respectively, corresponding to a mediated percentage of 10.1% (95% CI: 7.1-15.4%). The mediation effect was limited to men. CONCLUSIONS: The mediation effect of the combined lifestyle factors on the relationship between education and GC is modest. Other potential pathways explaining that relationship warrants further investigation.

Tea consumption and gastric cancer: a pooled analysis from the Stomach cancer Pooling (StoP) Project consortium.

BACKGROUND: Evidence from epidemiological studies on the role of tea drinking in gastric cancer risk remains inconsistent. We aimed to investigate and quantify the relationship between tea consumption and gastric cancer in the Stomach cancer Pooling (StoP) Project consortium. METHODS: A total of 9438 cases and 20,451 controls from 22 studies worldwide were included. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of gastric cancer for regular versus non-regular tea drinkers were estimated by one and two-stage modelling analyses, including terms for sex, age and the main recognised risk factors for gastric cancer. RESULTS: Compared to non-regular drinkers, the estimated adjusted pooled OR for regular tea drinkers was 0.91 (95% CI: 0.85-0.97). When the amount of tea consumed was considered, the OR for consumption of 1-2 cups/day was 1.01 (95% CI: 0.94-1.09) and for >3 cups/day was 0.91 (95% CI: 0.80-1.03). Stronger inverse associations emerged among regular drinkers in China and Japan (OR: 0.67, 95% CI: 0.49-0.91) where green tea is consumed, in subjects with H. pylori infection (OR: 0.68, 95% CI: 0.58-0.80), and for gastric cardia cancer (OR: 0.64, 95% CI: 0.49-0.84). CONCLUSION: Our results indicate a weak inverse association between tea consumption and gastric cancer.

Allium vegetables intake and the risk of gastric cancer in the Stomach cancer Pooling (StoP) Project.

BACKGROUND: The role of allium vegetables on gastric cancer (GC) risk remains unclear. METHODS: We evaluated whether higher intakes of allium vegetables reduce GC risk using individual participant data from 17 studies participating in the "Stomach cancer Pooling (StoP) Project", including 6097 GC cases and 13,017 controls. Study-specific odds ratios (ORs) were pooled using a two-stage modelling approach. RESULTS: Total allium vegetables intake was inversely associated with GC risk. The pooled OR for the highest versus the lowest study-specific tertile of consumption was 0.71 (95% confidence interval, CI, 0.56-0.90), with substantial heterogeneity across studies (I2 > 50%). Pooled ORs for high versus low consumption were 0.69 (95% CI, 0.55-0.86) for onions and 0.83 (95% CI, 0.75-0.93) for garlic. The inverse association with allium vegetables was evident in Asian (OR 0.50, 95% CI, 0.29-0.86) but not European (OR 0.96, 95% CI, 0.81-1.13) and American (OR 0.66, 95% CI, 0.39-1.11) studies. Results were consistent across all other strata. CONCLUSIONS: In a worldwide consortium of epidemiological studies, we found an inverse association between allium vegetables and GC, with a stronger association seen in Asian studies. The heterogeneity of results across geographic regions and possible residual confounding suggest caution in results interpretation.

Adult lifetime body mass index trajectories and endometrial cancer risk.

OBJECTIVE: To identify body mass index (BMI) trajectories in adult life and to examine their association with endometrial cancer (EC) risk, also exploring whether relations differ by hormonal replacement therapy use. DESIGN: Pooled analysis of two case-control studies. SETTING: Italy and Switzerland. POPULATION: A total of 458 EC cases and 782 controls. METHODS: We performed a latent class growth model to identify homogeneous BMI trajectories over six decades of age, with a polynomial function of age. Odds ratios (ORs) and the corresponding 95% CI for EC risk were derived through a multiple logistic regression model, correcting for classification error. MAIN OUTCOME MEASURES: The relation of BMI trajectories with endometrial cancer. RESULTS: We identified five BMI trajectories. Compared with women in the 'Normal weight-stable' trajectory, a reduction by about 50% in the risk of EC emerged for those in the 'Underweight increasing to normal weight' (95% CI 0.28-0.99). The 'Normal weight increasing to overweight' and the 'Overweight-stable' trajectories were associated with, respectively, an excess of 3% (95% CI 0.66-1.60) and of 71% (95% CI 1.12-2.59) in cancer risk. The OR associated to the trajectory 'Overweight increasing to obese' was 2.03 (95% CI 1.31-3.13). Stronger effects emerged among hormonal replacement therapy never users (OR 2.19 for the 'Overweight-stable' trajectory and OR 2.49 for the 'Overweight increasing to obese' trajectory). CONCLUSIONS: Our study suggests that longer exposure to overweight and obesity across a lifetime is associated with an increased risk of endometrial cancer. Weight during adulthood also appears to play an important role. TWEETABLE ABSTRACT: Longer exposure to overweight and obesity across a lifetime is associated with an increased risk of endometrial cancer.

Obstetric and neonatal outcomes in women with pregnancy associated cancer: a population-based study in Lombardy, Northern Italy.

BACKGROUND: Pregnancy associated cancer (PAC) may lead to adverse obstetric and neonatal outcomes. This study aims to assess the association between PACs and adverse perinatal outcomes [i.e. labor induction, iatrogenic delivery, preterm birth, small for gestational age (SGA) newborn, low Apgar score, major malformations, perinatal mortality] in Lombardy, Northern Italy. METHODS: This population-based historic cohort study used the certificate of delivery assistance and the regional healthcare utilization databases of Lombardy Region to identify beneficiaries of National Health Service who delivered between 2008 and 2017. PACs were defined through oncological ICD-9-CM codes reported in the hospital discharge forms. Each woman with PAC was matched to four women randomly selected from those cancer-free (1:4). Log-binomial regression models were fitted to estimate crude and adjusted prevalence ratio (aPR) and the corresponding 95% confidence interval (CI) of each perinatal outcome among PAC and cancer-free women. RESULTS: Out of the 657,968 deliveries, 831 PACs were identified (1.26 per 1000). PAC diagnosed during pregnancy was positively associated with labor induction or planned delivery (aPR=1.80, 95% CI: 1.57-2.07), cesarean section (aPR=1.78, 95% CI: 1.49-2.11) and premature birth (aPR=6.34, 95% CI: 4.59-8.75). No association with obstetric outcomes was found among PAC diagnosed in the post-pregnancy. No association of PAC, neither during pregnancy nor in post-pregnancy was found for SGA (aPR=0.71, 95% CI: 0.36-1.35 and aPR=1.04, 95% CI: 0.78-1.39, respectively), but newborn among PAC women had a lower birth weight (p-value< 0.001). Newborns of women with PAC diagnosed during pregnancy had a higher risk of borderline significance of a low Apgar score (aPR=2.65, 95% CI: 0.96-7.33) as compared to cancer-free women. CONCLUSION: PAC, especially when diagnosed during pregnancy, is associated with iatrogenic preterm delivery, compromising some neonatal heath indicators.

Dietary patterns and oesophageal cancer: a multi-country latent class analysis.

BACKGROUND: The considerable differences in food consumption across countries pose major challenges to the research on diet and cancer, due to the difficulty to generalise and reproduce the dietary patterns identified in a specific population. METHODS: We analysed data from a multicentric case-control study on oesophageal squamous cell carcinoma (ESCC) carried out between 1992 and 2009 in three Italian areas and in the Canton of Vaud, Switzerland, which included 505 cases and 1259 hospital controls. Dietary patterns were derived applying LCA on 24 food groups, controlling for country membership, and non-alcoholic energy intake. A multiple logistic regression model was used to derive odds ratio (ORs) and corresponding 95% CIs for ESCC according to the dietary patterns identified, correcting for classification error. RESULTS AND CONCLUSION: We identified three dietary patterns. The 'Prudent' pattern was distinguished by a diet rich in fruits and vegetables. The 'Western' pattern was characterised by low consumption of these food groups and higher intakes of sugar. The 'Lower consumers-combination pattern' exhibited a diet poor in most of the nutrients, preferences for fish, potatoes, meat and a few specific types of vegetables. Differences between Italy and Switzerland emerged for pattern sizes and for specific single food preferences. Compared to the 'Prudent' pattern, the 'Western' and the 'Lower consumers-combination' patterns were associated with an increased risk of ESCC (OR=3.04, 95% CI=2.12-4.38 and OR=2.81, 95% CI=1.65-4.76).

Frequency of Pregnancy-Associated Cancer: A Systematic Review of Population-Based Studies.

Despite numerous available resources of evidence, the results about the frequency of pregnancy-associated cancer (PAC) still show poor comparability due to dissimilarities in the study design and methodology, inclusion criteria, incoherent duration of follow-up and a heterogeneous reference population. We conducted a systematic review of population-based studies on PAC published up to December 2019, to provide updated research on this topic, highlighting strengths and limitations. Of the 24 papers included, 11 considered all types of tumors and 13 dealt with specific types of cancer. Differences in the procedures for estimating the frequency of PAC emerged even among population studies. However, we found consistent results for overall frequency of PAC- around 1/1000 pregnancies. Our review suggests that about 25% of PAC cases are diagnosed during pregnancy, confirming the hypothesis of an excess of diagnosis in the postpregnancy period. Sparse and inconsistent results were found regarding a potential increase in the frequency of PAC over calendar years. Alignments in the strategy to identify PAC are needed to overcome methodological weaknesses.

Reproducibility of A Posteriori Dietary Patterns across Time and Studies: A Scoping Review.

Few studies have considered if a posteriori dietary patterns (DPs) are generalizable across different centers or studies, or if they are consistently seen over time. To date, no systematic search of the literature on these topics has been carried out. A scoping review was conducted through a systematic search on the PubMed database. In the current review, we included the 34 articles examining the extent to which a posteriori DPs were consistently seen: 1) across centers from the same study or across different studies potentially representing different populations or countries (here indicated as cross-study reproducibility) and 2) over longer time periods (i.e., ≥2 y) (here indicated as stability over time). Selected articles (published in 1981-2019, 32% from 2010 onwards) were based on observational studies, mostly from Europe and North America. Five articles were based on children and/or adolescents and 14 articles included adults (2 men; 12 women, of whom 3 were pregnant women). A posteriori DPs were mostly derived (32 articles) with principal component or factor analyses. Among the 9 articles assessing DP reproducibility across studies (number of centers/studies: 2-27; median: 3), 5 provided a formal assessment using statistical methods (4 index-based approaches of different complexity, 1 statistical model). A median of 4 DPs was reproduced across centers/studies (range: 1-7). Among the 25 articles assessing DP stability over time (number of time-occasions: 2-6; median: 3), 19 provided a formal assessment with statistical methods (17 index-based and/or test-based approaches, 1 statistical model, 1 with both strategies). The number and composition of DPs remained mostly stable over time. Based on the limited evidence collected, most identified DPs showed good reproducibility across studies and stability over time. However, when present within the single studies, the criteria for the formal assessment of cross-study reproducibility or stability over time were generally very basic.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research Recommendations and the Risk of Breast Cancer.

The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) introduced in 2007, and updated in 2018, nutrition-related recommendations for cancer prevention. Previous studies generally reported inverse associations of breast cancer with the 2007 recommendations, while no study has yet evaluated the association with the 2018 guidelines. We investigated the association between adherence to the 2018 WCRF/AICR recommendations and breast cancer risk in a case-control study from Italy and Switzerland (1991-2008) including 3034 incident histologically-confirmed breast cancer cases and 3392 hospital controls. Adherence to the 2018 guidelines was summarized through a score incorporating eight recommendations (body fatness, physical activity, consumption of wholegrains/vegetables/fruit/beans, "fast foods" and other processed foods high in fat, starches, or sugars, red/processed meat, sugar-sweetened drinks, alcohol, breastfeeding), with higher scores indicating higher adherence. Odds ratios (OR) were estimated using multiple logistic regression models. We also conducted a meta-analysis including 15 additional studies using random-effects models. In our case-control study, adherence to the 2018 WCRF/AICR guidelines was inversely associated with breast cancer, with ORs of 0.60 (95% confidence interval (CI), 0.51-0.70) for a score ≥5.5 vs. ≤4.25, and of 0.83 (95% CI, 0.79-0.88) for a 1-point increment. In our study, 25% of breast cancers were attributable to low-to-moderate guideline adherence. In the meta-analysis, the pooled relative risks (RRs) were 0.73 (95% CI, 0.65-0.82, p heterogeneity among studies< 0.001) for the highest vs. the lowest WCRF/AICR score category, and 0.91 (95% CI, 0.88-0.94, p heterogeneity < 0.001) for a 1-point increment. This work provides quantitative evidence that higher adherence to the WCRF/AICR recommendations reduces the risk of breast cancer, thus opening perspectives for prevention.

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-control study (1992-2004) 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 "Animal products", "Starch-rich", "Vitamins and fiber", and "Cooking oils and dressings". Higher intakes of the "Starch-rich" pattern were positively associated with RCC risk (OR = 1.38, 95% CI: 1.04-1.82 for the highest quartile, p = 0.018). The association was inverse with the "Cooking oils and dressings" pattern (OR = 0.61, 95% CI: 0.47-0.80, p < 0.001), whereas no association was found with "Animal products" and "Vitamins and fiber" patterns. CONCLUSIONS: Higher intakes of starch-related foods may increase RCC risk, whereas consumption of olive and seed oils may favorably influence RCC risk.

Reproducibility and Validity of A Posteriori Dietary Patterns: A Systematic Review.

The effective use of dietary patterns (DPs) remains limited. There is a need to assess their consistency over multiple administrations of the same dietary source, different dietary sources, or across different studies. Similarly, their generalizability should be based on a previous assessment of DP construct validity. However, to date, no systematic reviews of reproducibility and validity of a posteriori DPs have been carried out. In addition, several methodological questions related to their identification are still open and prevent a fair comparison of epidemiological results on DPs and disease. A systematic review of the literature on the PubMed database was conducted. We identified 218 articles, 64 of which met the inclusion criteria. Of these, the 38 articles dealing with reproducibility and relative and construct validity of DPs were included. These articles (published in 1999-2017, 53% from 2010 onwards) were based on observational studies conducted worldwide. The 14 articles that assessed DP reproducibility across different statistical solutions examined different research questions. Included were: the number of food groups or subjects; input variable format (as well as adjustment for energy intake); algorithms and the number of DPs to retain in cluster analysis; rotation method; and score calculation in factor analysis. However, we identified at most 3 articles per research question on DP reproducibility across statistical solutions. From another 15 articles, reproducibility of DPs over shorter (≤1 y) time periods was generally good and higher than DP relative validity (as measured across different dietary sources). Confirmatory factor analysis was used in 15 of the included articles. It provided reassuring results in identifying valid dietary constructs characterizing the populations under consideration. Based on the available evidence, only suggestive conclusions can be derived on reproducibility across different statistical solutions. Nevertheless, most identified DPs showed good reproducibility, fair relative validity, and good construct validity.