Piet A. van Den Brandt

Background: Processed meat is classified as a carcinogen and unprocessed red meat a probable carcinogen, but their associations with stomach cancer are not established. We evaluated intakes of these food groups and poultry, seafood, and eggs in relation to stomach cancer risk. Methods: Individual-level data for 1 100 370 females and 891 919 males from 20 cohorts were analysed. Diet was assessed at baseline by using food-frequency questionnaires or diet histories generally covering the past year and harmonized across studies. We used Cox regression to estimate multivariable-adjusted study- and sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with each food group and combined study-specific estimates by using random-effects meta-analysis. We repeated analyses using an aggregated dataset combining all studies. Results: During follow-up (mean = 8–23 years across studies), 8561 invasive gastric adenocarcinomas were diagnosed. Processed meat intake showed weak evidence of an overall association with stomach cancer risk (HR, 1.15 for ≥45 vs <3 g/day; 95% CI, 1.00–1.32 and HR, 1.03 per 25-g/day increment; 95% CI, 0.99–1.07). This association was limited to current smokers (Pinteraction = .01) and differed by geographic region, with evidence for an association in Australian and European studies and no association observed in Asian studies (Pinteraction = .02). Positive associations with stomach cancer were observed for egg intake; no association was found for unprocessed red meat, poultry, or seafood. Conclusion: Higher processed meat intake was associated with a modestly increased risk of stomach cancer among current smokers, although residual confounding by smoking dose remains possible. Findings for eggs warrant further investigation.

Background: Processed meat and unprocessed red meat are considered carcinogenic and ‘probably carcinogenic’ to humans, respectively, but findings for bladder cancer remain inconsistent. Objectives: We assessed associations between processed meat and unprocessed red meat intake and bladder cancer risk using data from the Pooling Project of Prospective Studies of Diet and Cancer. Methods: Associations with bladder cancer risk were assessed using individual-level data from 30 cohort studies from North America, Europe, Australia and Asia. Diet was assessed at enrolment using validated food frequency questionnaires or diet histories. Following a pre-specified analysis plan, study- and sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression, adjusted for smoking status and duration and other potential confounders, and pooled using inverse-variance-weighted random-effects meta-analysis. Results: During median follow-up across cohorts of 8–29 years, among 2,575,971 participants, 20,780 were diagnosed with bladder cancer. Processed meat intake was associated with increased bladder cancer risk (HR comparing ≥40 with <5 g/day = 1.08; 95% CI: 1.02–1.15; HR per 20 g/day = 1.02; 95% CI: 1.00–1.03). Weaker evidence of association with increased risk was also observed for unprocessed red meat (HR comparing ≥100 with <20 g/day = 1.06; 95% CI: 1.00–1.13; HR per 50 g/day = 1.01; 95% CI: 0.99–1.03). There was no evidence of heterogeneity by study, sex, or region. Conclusions: Higher intakes of processed meat and unprocessed red meat were associated with a small increase in risk of bladder cancer. These findings are consistent with existing public health recommendations to limit consumption of red and processed meat.

Supplementary Table S1. Age-adjusted hazard ratios and 95% confidence intervals for the association between body mass index and risk of SARIFA-positive and SARIFA-negative colorectal cancer, stratified by sex and tumor location.

Supplementary Table S2. Age-adjusted hazard ratios and 95% confidence intervals for the association between lower-body clothing size (as a proxy for adiposity) and risk of SARIFA-positive and SARIFA-negative colorectal cancer, stratified by sex and tumor location.

Background:Stroma AReactive Invasion Front Areas (SARIFA) are a histopathologic biomarker characterized by a direct tumor–adipocyte contact at the tumor invasion front. Although the tumor-promoting effect of tumor–adipocyte interactions has often been linked to obesity, it is unclear whether prediagnostic energy balance–related factors are differentially associated with the risk of SARIFA-positive versus SARIFA-negative colorectal cancers. Methods:We analyzed data from the Netherlands Cohort Study, including 120,852 participants and 1,826 incident colorectal cancer cases with known SARIFA status. Multivariable-adjusted Cox regression was used to estimate associations between baseline prediagnostic body mass index (BMI), lower-body clothing size as a proxy for waist circumference, and nonoccupational physical activity and colon and rectal cancer risk by SARIFA status. Results:In men, BMI was more strongly associated with the risk of SARIFA-positive colon cancer [hazard ratio (HR) per 5 kg/m2, 1.57; 95% confidence interval (CI), 1.20–2.07] than SARIFA-negative tumors (HR, 1.22; 95% CI, 1.01–1.48), with similar patterns for lower-body clothing size. In women, weaker associations were observed, but estimates were again higher for SARIFA-positive tumors than SARIFA-negative tumors. Physical activity was inversely associated with SARIFA-positive colon cancer in women (HR per 30 minutes/day, 0.92; 95% CI, 0.85–1.01), but not SARIFA-negative tumors, with no clear SARIFA-specific patterns in men or for rectal cancer. Conclusions:Findings suggest a stronger role of body fatness in the development of SARIFA-positive than SARIFA-negative colon cancer and provide novel evidence warranting confirmation in other molecular pathologic epidemiology studies. Impact:This study extends previous epidemiologic findings by suggesting that adiposity may influence colon cancer development, resulting in a specific tumor–stroma interaction phenotype.

Supplementary Table S3. Age-adjusted hazard ratios and 95% confidence intervals for the association between non-occupational physical activity and risk of SARIFA-positive and SARIFA-negative colorectal cancer, stratified by sex and tumor location.

Background: Stroma AReactive Invasion Front Areas (SARIFA) are a histopathologic biomarker characterized by a direct tumor-adipocyte interaction at the tumor invasion front. While the tumor promoting effect of tumor-adipocyte interactions has often been linked to obesity, it is unclear whether pre-diagnostic energy balance-related factors are differentially associated with the risk of SARIFA-positive versus SARIFA-negative colorectal cancers (CRC). Methods: We analyzed data from the Netherlands Cohort Study, including 120,852 participants and 1,826 incident CRC cases with known SARIFA status. Multivariable-adjusted Cox regression was used to estimate associations between baseline pre-diagnostic BMI, lower-body clothing size as a proxy for waist circumference, and non-occupational physical activity and colon and rectal cancer risk by SARIFA status. Results: In men, BMI was more strongly associated with risk of SARIFA-positive colon cancer (HR per 5 kg/m²: 1.57, 95%CI 1.20-2.07) than SARIFA-negative tumors (HR: 1.22, 95%CI 1.01-1.48), with similar patterns for lower-body clothing size. In women, weaker associations were observed but estimates were again higher for SARIFA-positive tumors than SARIFA-negative tumors. Physical activity was inversely associated with SARIFA-positive colon cancer in women (HR per 30 min/day: 0.92, 95%CI 0.85-1.01), but not SARIFA-negative tumors, with no clear SARIFA-specific patterns in men or for rectal cancer. Conclusions: Findings suggest a stronger role of body fatness in the development of SARIFA-positive than SARIFA-negative colon cancer, and provide novel evidence warranting confirmation in other molecular pathological epidemiology studies. Impact: This study extends previous epidemiological findings by suggesting that adiposity may influence colon cancer development, resulting in a specific tumor-stroma interaction phenotype.

Although evidence suggests that a positive family history of bladder cancer in first-degree relatives is an important risk factor for bladder cancer occurrence, results remain unclear. The influence of family history of nonbladder cancers and more distant relatives on bladder cancer risk is inconsistent. This research, therefore, aims to increase the understanding of the association between family history and bladder cancer risk based on worldwide case–control studies. In total 4,327 cases and 8,948 non-cases were included. Pooled ORs, with corresponding 95% confidence intervals (CI), were obtained using multilevel logistic regression models, adjusted by age, sex, ethnicity, smoking status, and smoking pack-years. The results show bladder cancer risk increased by having a first- or second-degree relative affected with bladder cancer (OR, 2.72; 95% CI, 1.55–4.77 and OR, 1.71; 95% CI, 1.22–2.40, respectively), and nonurologic cancers (OR, 1.61; 95% CI, 1.19–2.18). Moreover, bladder cancer risk increased by number of cancers affected first-degree relatives (for 1 and >1 first-degree relatives: OR, 1.42; 95% CI, 1.02–2.04; OR, 2.67; 95% CI, 1.84–3.86, respectively). Our findings highlight an increased bladder cancer risk for a positive bladder cancer family history in first- and second-degree relatives, and indicate a possible greater effect for an increment of numbers of affected relatives.Prevention Relevance:This study found a positive association between family history and bladder cancer in first- and second-degree relatives, with an added effect attributed to smoking. Given the detriments of bladder cancer, at-risk individuals should receive family history screening and tobacco cessation and avoidance counseling.

Supplementary Figure from Family History and Risk of Bladder Cancer: An Analysis Accounting for First- and Second-degree Relatives

Supplementary data from Energy Balance–Related Factors and Risk of Colorectal Cancer Expressing Different Levels of Proteins Involved in the Warburg Effect