Trends in diffuse type of gastric cancer: focus on younger women.

BACKGROUND: Gastric cancer (GC) incidence has been decreasing over the last decades; however, there are uncertainties in trends and proportional distribution of the diffuse type. METHODS: GC incidence data were extracted from the population-based Friuli Venezia Giulia Cancer Registry. GC types (diffuse vs. others) were compared in relation to age at diagnosis, calendar years, and sexes. RESULTS: Between 1995 and 2021, diffuse GC accounted for 10.2% of all GCs. The proportion was greater among individuals aged <45 years, 34.0% in women and 25.7% in men. An increasing proportion over time was observed, in particular in women (from 9.9% in 1995-2000 to 14.10% during 2011-2021). In the last decade (2011-2021), a decreasedincidence of all GC was observed, reaching an age-standardized rate (world standard) of 1.4/100,000 for men and 1.2/100,000 for women. Rates of diffuse GC were 0.3/100,000 in younger population. CONCLUSION: Although the overall GC incidence is decreasing, the percentage of diffuse GC is increasing in the younger population, particularly in women. Reasons for the increased proportion of diffuse-type GC within younger women remain uncertain, possibly related to the decreased exposure to risk factors for other GC histotypes.

Physical activity and exercise health benefits: cancer prevention, interception, and survival.

Physical activity (PA) has an established role in the promotion of health and fitness and the prevention of disease. Expected overall benefits include reduction of all-cause morbidity and death, weight control, improved quality of life, improved bone health and decreased falls of elderly subjects, , deeper cognition, and reduced risk of depression, anxiety, and sleeplessness. Currently, PA is a mainstay in the management of cardiovascular diseases, metabolic syndrome, diabetes, and bone health. Recently, the perception of its role in primary and secondary prevention, interception, and treatment of cancer, however, is also gaining importance. Regular walking, the simplest type of PA, is associated with reduced all-cause and cardiovascular disease mortality, and a role in cancer prevention is of increasing interest. Furthermore, PA improves the quality of life of cancer patients, attenuating side effects of chemotherapy, decreasing sarcopenia, increasing fitness, and inhibiting the recurrence and progression of some cancer types. It promotes emotional and psychological benefits in patients, inducing positive changes. While mechanisms, effective levels and useful amount of PA practice are well established in cardiology, they are yet to be fully determined in oncology. Nevertheless, PA is recommended to reduce cancer risk in the general population, and it has been introduced in programs for the prevention of second cancers. In perspective, it will help as integrative therapy in cancer patients and for cancer survivors. The number of beneficial effects in the cancer continuum is highlighted in this review.

Invasive lobular breast cancer: Focus on prevention, genetics, diagnosis, and treatment.

Invasive lobular cancer (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast malignancies. The distinctive biological features of ILC include the loss of the cell adhesion molecule E-cadherin, which drives the tumor's peculiar discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, such tumors originate in the lobules, are more commonly bilateral compared to invasive ductal cancer (IDC) and require a more accurate diagnostic examination through imaging. They are luminal in molecular subtype, and exhibit estrogen and progesterone receptor positivity and HER2 negativity, thus presenting a more unpredictable response to neoadjuvant therapies. There has been a significant increase in research focused on this distinctive breast cancer subtype, including studies on its pathology, its clinical and surgical management, and the high-resolution definition of its genomic profile, as well as the development of new therapeutic perspectives. This review will summarize the heterogeneous pattern of this unique disease, focusing on challenges in its comprehensive clinical management and on future insights and research objectives.

Fiber-type prebiotics and gynecological and breast cancers risk: the PrebiotiCa study.

Prebiotics may influence the risk of hormone-related female cancers by modulating the gut microbiota involved in estrogens metabolism. We evaluated the association of fiber-type prebiotic intake with breast, endometrial, and ovarian cancers. Data derived from a network of Italian hospital-based case-control studies (1991-2006), including 2560 cases of cancer of the breast (2588 controls), 454 of the endometrium (908 controls) and 1031 of the ovary (2411 controls). Inulin-type fructans (ITFs), and selected fructo-oligosaccharides (FOSs, nystose, kestose and 1F-ß-fructofuranosylnystose) and galacto-oligosaccharides (GOSs, raffinose and stachyose) were quantified in food products. Prebiotic intake was estimated by multiplying food frequency questionnaire intake by the foods' prebiotic content. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were derived by multiple logistic regression models. Nystose intake was marginally directly associated with breast (OR for the 4th versus the 1st quartile 1.20, 95% CI: 1.00-1.45), ovarian (OR 1.39, 95% CI: 1.04-1.84) and endometrial cancer risk (OR 1.32, 95% CI: 0.85-2.03). High 1F-ß-fructofuranosylnystose intake was inversely associated with ovarian cancer (OR 0.67, 95% CI: 0.52-0.85). ITFs, kestose, raffinose and stachyose were not associated with the three cancers. The intake of most fiber-type prebiotics was not appreciably and consistently associated with breast, endometrial and ovarian cancer risks.

Fruits and vegetables intake and bladder cancer risk: a pooled analysis from 11 case-control studies in the BLadder cancer Epidemiology and Nutritional Determinants (BLEND) consortium.

PURPOSE: High consumption of fruits and vegetables decrease the risk of bladder cancer (BC). The evidence of specific fruits and vegetables and the BC risk is still limited. METHODS: Fruit and vegetable consumptions in relation to BC risk was examined by pooling individual participant data from case-control studies. Unconditional logistic regression was used to estimate study-specific odds ratio's (ORs) with 95% confidence intervals (CIs) and combined using a random-effects model for intakes of total fruits, total vegetables, and subgroups of fruits and vegetables. RESULTS: A total of 11 case-control studies were included, comprising 5637 BC cases and 10,504 controls. Overall, participants with the highest intakes versus the lowest intakes of fruits in total (OR 0.79; 95% CI 0.68-0.91), citrus fruits (OR 0.81; 95% CI 0.65-0.98), pome fruits (OR 0.76; 95% CI 0.65-0.87), and tropical fruits (OR 0.84; 95% CI 0.73-0.94) reduced the BC risk. Greater consumption of vegetables in total, and specifically shoot vegetables, was associated with decreased BC risk (OR 0.82; 95% CI 0.68-0.96 and OR 0.87; 95% CI 0.78-0.96, respectively). Substantial heterogeneity was observed for the associations between citrus fruits and total vegetables and BC risk. CONCLUSION: This comprehensive study provides compelling evidence that the consumption of fruits overall, citrus fruits, pome fruits and tropical fruits reduce the BC risk. Besides, evidence was found for an inverse association between total vegetables and shoot vegetables intake.

Ultraprocessed foods and cancer risk: the importance of distinguishing ultraprocessed food groups.

Several case-control, cohort studies, and meta-analyses found a moderate association between ultraprocessed food consumption and the risk of colorectal and a few other cancers. The evidence is, however, not consistent. A reason for such inconsistence is that the NOVA classification of ultraprocessed foods may include unfavorable but also favorable dietary components, and it may vary across different populations.

The protective effect of dietary folate intake on gastric cancer is modified by alcohol consumption: A pooled analysis of the StoP Consortium.

Dietary folate intake has been identified as a potentially modifiable factor of gastric cancer (GC) risk, although the evidence is still inconsistent. We evaluate the association between dietary folate intake and the risk of GC as well as the potential modification effect of alcohol consumption. We pooled data for 2829 histologically confirmed GC cases and 8141 controls from 11 case-control studies from the international Stomach Cancer Pooling Consortium. Dietary folate intake was estimated using food frequency questionnaires. We used linear mixed models with random intercepts for each study to calculate adjusted odds ratios (OR) and 95% confidence interval (CI). Higher folate intake was associated with a lower risk of GC, although this association was not observed among participants who consumed >2.0 alcoholic drinks/day. The OR for the highest quartile of folate intake, compared with the lowest quartile, was 0.78 (95% CI, 0.67-0.90, P-trend = 0.0002). The OR per each quartile increment was 0.92 (95% CI, 0.87-0.96) and, per every 100 µg/day of folate intake, was 0.89 (95% CI, 0.84-0.95). There was a significant interaction between folate intake and alcohol consumption (P-interaction = 0.02). The lower risk of GC associated with higher folate intake was not observed in participants who consumed >2.0 drinks per day, ORQ4v Q1 = 1.15 (95% CI, 0.85-1.56), and the OR100 µg/day = 1.02 (95% CI, 0.92-1.15). Our study supports a beneficial effect of folate intake on GC risk, although the consumption of >2.0 alcoholic drinks/day counteracts this beneficial effect.

Dietary intake of copper and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Evidence on the potential association between dietary copper intake and gastric cancer (GC) is lacking. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project-an international consortium of epidemiological studies on GC. METHODS: Data from five case-control studies within the StoP Project were included (2448 cases, 4350 controls). We estimated adjusted odds ratios (ORs) and 95% CIs for the association between dietary copper intake and GC using multivariable mixed-effects logistic regression models. We also modelled the dose-response relationship between copper intake and GC using a logistic mixed-effects model with fractional polynomial. RESULTS: The OR for the highest quartile of copper intake compared with the lowest one was 0.78 (95% CI: 0.63-0.95; P for trend = 0.013). Results were similar for non-cardia-type (OR: 0.72; 95% CI: 0.57-0.91), intestinal-type (OR: 0.75; 95% CI: 0.56-0.99) and other histological-type GC (OR: 0.65; 95% CI: 0.44-0.96). The dose-response analysis showed a steep decrease in ORs for modest intakes (<1 mg/day), which were subsequently steady for ≤3 mg/day (OR: 0.09; 95% CI: 0.02-0.41) and slowly increased for higher intakes. CONCLUSIONS: The findings of our large study suggest that copper intake might be inversely associated with GC, although their confirmation by prospective studies is required.

CDH1 Genotype Exploration in Women With Hereditary Lobular Breast Cancer Phenotype.

Importance: Pathogenic or likely pathogenic (P/LP) germline CDH1 variants are associated with risk for diffuse gastric cancer and lobular breast cancer (LBC) in the so-called hereditary diffuse gastric cancer (HDGC) syndrome. However, in some circumstances, LBC can be the first manifestation of this syndrome in the absence of diffuse gastric cancer manifestation. Objectives: To evaluate the frequency of germline CDH1 variants in women with the hereditary LBC (HLBC) phenotype, somatic CDH1 gene inactivation in germline CDH1 variant carriers' tumor samples, and the association of genetic profiles with clinical-pathological data and survival. Design, Setting, and Participants: This single-center, longitudinal, prospective cohort study was conducted from January 1, 1997, to December 31, 2021, with follow-up until January 31, 2023. Women with LBC seen at the European Institute of Oncology were included. Testing for germline CDH1, BRCA1, and BRCA2 genes was performed. Somatic profiling was assessed for germline CDH1 carriers. Main Outcomes and Measures: Accurate estimates of prevalence of germline CDH1 variants among patients with HLBC and the association of somatic sequence alteration with HLBC syndrome. The Kaplan-Meier method and a multivariable Cox proportional hazards regression model were applied for overall and disease-free survival analysis. Results: Of 5429 cases of primary LBC, familial LBC phenotype accounted for 1867 (34.4%). A total of 394 women with LBC were tested, among whom 15 germline CDH1 variants in 15 unrelated families were identified. Among these variants, 6 (40.0%) were P/LP, with an overall frequency of 1.5% (6 of 394). Of the 6 probands with P/LP CDH1 LBC, 5 (83.3%) had a positive family history of BC and only 1 (16.7%) had sporadic juvenile early-onset LBC. No germline BRCA1 and BRCA2 variants were identified in CDH1 carriers. An inactivating CDH1 mechanism (second hit) was identified in 4 of 6 explored matched tumor samples (66.7%) in P/LP germline carriers. The P/LP CDH1 LBC variant carriers had a significantly lower age at diagnosis compared with the group carrying CDH1 variants of unknown significance or likely benign (42.5 [IQR, 38.3-43.0] vs 51.0 [IQR, 45.0-53.0] years; P = .03). Conclusions and Relevance: In this cohort study, P/LP germline CDH1 variants were identified in individuals not fulfilling the classic clinical criteria for HDGC screening, suggesting that identification of these variants may provide a novel method to test women with LBC with early age at diagnosis and/or positive family history of BC.

Cancer mortality predictions for 2024 in selected Asian countries and Australia with focus on stomach cancer.

INTRODUCTION: We estimated cancer mortality figures in five major Asian countries and Australia for 2024, focusing on stomach cancer, a leading cause of cancer-related deaths in Eastern Asia. METHODS: We computed country- and sex-specific annual age-standardized rates (ASRs) for total cancers and the 10 most common cancer sites, using WHO and the United Nations Population Division databases from 1970 to 2021 or the latest available year. We predicted figures for 2024 and estimated the number of avoided cancer deaths in 1994-2024. RESULTS: All cancers combined ASR declined between 2015-2019 and 2024 across considered countries and sexes. In 2024, the lowest predicted male rate is in the Philippines (75.0/100 000) and the highest in Australia (94.2/100 000). The Republic of Korea is predicted to have the lowest female ASR (42.1/100 000) while the Philippines the highest (74.5/100 000). Over the last three decades, 121 300 deaths were estimated to be avoided in Hong Kong SAR, 69 500 in Israel, 1 246 300 in Japan, 653 300 in the Republic of Korea, 303 300 in Australia, and 89 700 among Philippine men. Mortality from stomach cancer has been decreasing since 1970 in all considered countries and both sexes. Significant decreases are at all age groups Male rates remain, however, high in Japan (8.7/100 000) and the Republic of Korea (6.2/100 000). CONCLUSION: Declining cancer mortality is predicted in the considered countries, notably reducing stomach cancer burden. Stomach cancer, however, remains a major public health issue in East Asia.

The association between dietary fiber intake and gastric cancer: a pooled analysis of 11 case-control studies.

PURPOSE: Gastric cancer (GC) is among the leading causes of cancer mortality worldwide. The objective of this study was to investigate the association between dietary fiber intake and GC. METHODS: We pooled data from 11 population or hospital-based case-control studies included in the Stomach Cancer Pooling (StoP) Project, for a total of 4865 histologically confirmed cases and 10,626 controls. Intake of dietary fibers and other dietary factors was collected using food frequency questionnaires. We calculated the odds ratios (OR) and 95% confidence intervals (CI) of the association between dietary fiber intake and GC by using a multivariable logistic regression model adjusted for study site, sex, age, caloric intake, smoking, fruit and vegetable intake, and socioeconomic status. We conducted stratified analyses by these factors, as well as GC anatomical site and histological type. RESULTS: The OR of GC for an increase of one quartile of fiber intake was 0.91 (95% CI: 0.85, 0.97), that for the highest compared to the lowest quartile of dietary fiber intake was 0.72 (95% CI: 0.59, 0.88). Results were similar irrespective of anatomical site and histological type. CONCLUSION: Our analysis supports the hypothesis that dietary fiber intake may exert a protective effect on GC.

Diabetes Risk Reduction Diet and Colorectal Cancer Risk.

BACKGROUND: Diabetes has been associated with colorectal cancer. We evaluated whether adherence to a diabetes risk reduction diet (DRRD) can favorably influence the risk of colorectal cancer. METHODS: Data came from a multicentric Italian case-control study including 1,953 histologically confirmed colorectal cancer cases and 4,154 hospital controls admitted for acute nonneoplastic diseases. Diet was assessed through a validated and reproducible food frequency questionnaire. The DRRD score was computed assigning higher values for higher consumption of cereal fiber, fruit, coffee, nuts and a higher polyunsaturated/saturated fats ratio and for lower glycemic index and lower consumption of red/processed meat and sweetened beverages and fruit juices. The ORs and the corresponding 95% confidence intervals (CI) of colorectal cancer according to the DRRD score were obtained using logistic regression models adjusting for total energy intake and other major confounders. RESULTS: The DRRD was inversely related to colorectal cancer risk. The ORs of colorectal cancer were 0.77 (95% CI, 0.67-0.89) for the third versus first score tertile (Ptrend < 0.001) and 0.92 (95% CI, 0.87-0.96) for a 3-point increment in the score. Inverse associations were observed for colon and rectal cancers and were consistent in strata of sex, age, and other major covariates. CONCLUSIONS: A higher adherence to a DRRD was inversely associated with colorectal cancer risk. IMPACT: Given the high incidence and mortality rates of colorectal cancer, adherence to a DRRD can have relevant prevention and public health implications.

Association of national smoke-free policies with per-capita cigarette consumption and acute myocardial infarction mortality in Europe.

BACKGROUND: Evidence on the association between smoke-free policies and per-capita cigarette consumption and mortality due to acute myocardial infarction (AMI) in Europe is limited. Hence, we aimed to assess this association and to evaluate which factors influence it. METHODS: We performed an interrupted time series analysis, including 27 member states of the European Union and the UK, on per-capita cigarette consumption and AMI mortality.A multivariate meta-regression was used to assess the potential influence of other factors on the observed associations. RESULTS: Around half of the smoke-free policies introduced were associated with a level or slope change, or both, of per-capita cigarette consumption and AMI mortality (17 of 35). As for cigarette consumption, the strongest level reduction was observed for the smoking ban issued in 2010 in Poland (rate ratio (RR): 0.47; 95% CI: 0.41, 0.53). Instead, the largest level reduction of AMI mortality was observed for the intervention introduced in 2012 in Bulgaria (RR: 0.38; 95% CI: 0.34, 0.42).Policies issued more recently or by countries with a lower human development index were found to be associated with a larger decrease in per-capita cigarette consumption. In addition, smoking bans applying to bars had a stronger inverse association with both cigarette consumption and AMI mortality. CONCLUSIONS: The results of our study suggest that smoke-free policies are effective at reducing per-capita cigarette consumption and AMI mortality. It is extremely important to monitor and register data on tobacco, its prevalence and consumption to be able to tackle its health effects with concerted efforts.

Dietary intake of vitamin C and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Previous studies suggest that dietary vitamin C is inversely associated with gastric cancer (GC), but most of them did not consider intake of fruit and vegetables. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project, a consortium of epidemiological studies on GC. METHODS: Fourteen case-control studies were included in the analysis (5362 cases, 11,497 controls). We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the association between dietary intake of vitamin C and GC, adjusted for relevant confounders and for intake of fruit and vegetables. The dose-response relationship was evaluated using mixed-effects logistic models with second-order fractional polynomials. RESULTS: Individuals in the highest quartile of dietary vitamin C intake had reduced odds of GC compared with those in the lowest quartile (OR: 0.64; 95% CI: 0.58, 0.72). Additional adjustment for fruit and vegetables intake led to an OR of 0.85 (95% CI: 0.73, 0.98). A significant inverse association was observed for noncardia GC, as well as for both intestinal and diffuse types of the disease. The results of the dose-response analysis showed decreasing ORs of GC up to 150-200 mg/day of vitamin C (OR: 0.54; 95% CI: 0.41, 0.71), whereas ORs for higher intakes were close to 1.0. CONCLUSIONS: The findings of our pooled study suggest that vitamin C is inversely associated with GC, with a potentially beneficial effect also for intakes above the currently recommended daily intake (90 mg for men and 75 mg for women).

Hypertension and Risk of Endometrial Cancer: A Pooled Analysis in the Epidemiology of Endometrial Cancer Consortium (E2C2).

BACKGROUND: The incidence rates of endometrial cancer are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for endometrial cancer. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of endometrial cancer remains unclear. In this study, we evaluated hypertension as an independent risk factor for endometrial cancer and whether this association is modified by other established risk factors. METHODS: We included 15,631 endometrial cancer cases and 42,239 controls matched on age, race, and study-specific factors from 29 studies in the Epidemiology of Endometrial Cancer Consortium. We used multivariable unconditional logistic regression models to estimate ORs and 95% confidence intervals (CI) to evaluate the association between hypertension and endometrial cancer and whether this association differed by study design, race/ethnicity, body mass index, diabetes status, smoking status, or reproductive factors. RESULTS: Hypertension was associated with an increased risk of endometrial cancer (OR, 1.14; 95% CI, 1.09-1.19). There was significant heterogeneity by study design (Phet < 0.01), with a stronger magnitude of association observed among case-control versus cohort studies. Stronger associations were also noted for pre-/perimenopausal women and never users of postmenopausal hormone therapy. CONCLUSIONS: Hypertension is associated with endometrial cancer risk independently from known risk factors. Future research should focus on biologic mechanisms underlying this association. IMPACT: This study provides evidence that hypertension may be an independent risk factor for endometrial cancer.

The global gastric cancer consortium: an update from the Stomach cancer Pooling (StoP) project.

We updated to December 2023 the main findings of the stomach cancer pooling (StoP) project including about 13 000 cases and 31 000 controls from 29 case-control and 5 nested studies. The StoP project quantified more precisely than previously available the positive associations of tobacco smoking, high alcohol consumption, meat intake, selected occupations (e.g. agricultural and miners), gastric ulcer and family history with gastric cancer and the inverse associations with socioeconomic status and selected aspects of diet (fruits, including citrus fruits, vegetables, including allium and mushrooms, and polyphenols). No consistent associations were found with coffee, yoghurt and leisure-time physical activity, metformin or proton pump inhibitors use.

Global trends in cutaneous malignant melanoma incidence and mortality.

Mortality from cutaneous malignant melanoma (CMM) increased in the past, but trends have been favorable in more recent years in many high-income countries. However, incidence has been increasing in several countries. We provided an up-to-date overview of mortality trends from CMM. We analyzed death certification data from the WHO in selected countries worldwide from 1980 to the most recent available calendar years. We also reported incidence data derived from Cancer Incidence in Five Continents from 1990 to 2012. Separate analyses were performed for young adults aged 20-44 and middle-aged adults aged 45-64 years. Mortality from CMM in all age groups showed a favorable pattern in the majority of the countries considered. Mortality trends declined by 40 to 50% in Australia over the last decades, confirming the importance of prevention measures. Considering young adults aged 20-44, Australia, New Zealand and Northern Europe reported the highest death rates for both sexes (>0.90/100 000 in men and >0.60/100 000 in women) while Japan, the Philippines, and Latin America the lowest ones (<0.50/100 000 and <0.35/100 000 in men and women, respectively). Incidence trends were stable or upward in most countries, with higher rates among women. Our study highlights a global reduction of CMM mortality over the last three decades. The increasing awareness of risk factors, mainly related to UV exposure, along with early diagnosis and progress in treatment for advanced disease played pivotal roles in reducing CMM mortality, particularly in Australia.

Legume intake and cancer risk in a network of case-control studies.

Evidence on the relationship between legume consumption and risk of specific cancer sites is inconclusive. We used data from a series of case-controls studies, conducted in Italy and in the Swiss Canton of Vaud between 1991 and 2009 to quantify the association between legume consumption and several cancer sites including oral cavity, esophagus, larynx, stomach, colorectum, breast, endometrium, ovary, prostate and kidney. Multiple logistic regression models controlled for sex, age, education, smoking, alcohol, body mass index, physical activity, comorbidities, and consumption of fruit, vegetables, processed meat and total calorie intake were used to estimate the odds ratios (OR) for different cancer sites and their corresponding 95% confidence intervals(CI). For female hormone-related cancers, the models also included adjustments for age at menarche, menopausal status and parity. Although most of the estimates were below unity, suggesting a protective effect, only colorectal cancer showed a significant association. Compared to no consumption, the OR for consuming at least one portion of legumes was 0.79 (95% CI: 0.68-0.91), the OR for consuming two or more portions was 0.68 (95% CI: 0.57-0.82) and the estimate for an increment of one portion per week was 0.87 (95% CI: 0.81-0.93). The inverse association between legume consumption and colorectal cancer suggests a possible role of legumes in preventing cancer risk.