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Background: Here, we explore the association between excess weight during early to mid-adulthood and survival in patients diagnosed with breast and colorectal cancer, using a pooled analysis of five cohort studies and study participants from 11 countries., Methods: Participant-level body mass index (BMI) trajectories were estimated by fitting a growth curve model using over 2 million repeated BMI measurements from close to 600,000 cohort participants. Cumulative measures of excess weight were derived. Data from over 23,000 patients with breast and colorectal cancer were subsequently analyzed using time-to-event models for death with the date of diagnosis as start of follow-up. Study-specific results were combined through a random effect meta-analysis., Results: We found a significant dose-response relationship ( P trend = 0.013) between the average BMI during early and mid-adulthood and death from breast cancer, with a pooled HR of 1.31 (1.07-1.60) and the time to death shortened by 16% for average BMI above 25 kg/m 2 compared with average BMI less than or equal to 22.5 kg/m 2 , respectively. Similar results were found for categories of cumulative time spent with excess weight. There was no association between excess body fatness during early to mid-adulthood and death in patients with colorectal cancer., Conclusions: Excess body fatness during early to mid-adulthood is associated not only with an increased risk of developing cancer, but also with a lower survival in patients with breast cancer., Impact: Our results emphasize the importance of public health policies aimed at reducing overweight during adulthood and inform future studies on the relationship between excess weight and cancer outcomes., (©2021 American Association for Cancer Research.)

Background: Previous prospective studies of associations between circulating inflammation-related molecules and pancreatic cancer risk have included limited numbers of markers., Methods: We conducted a case-cohort study nested within the Japan Public Health Center-based Prospective Study Cohort II. We selected a random subcohort ( n = 774) from a total of 23,335 participants aged 40 to 69 years who returned a questionnaire and provided blood samples at baseline. During the follow-up period from 1993 to 2010, we identified 111 newly diagnosed pancreatic cancer cases, including one case within the subcohort. Plasma concentrations of 62 inflammatory markers of chemokines, cytokines, and growth factors were measured by a Luminex fluorescent bead-based assay. Cox regression models were applied to estimate HR and 95% confidence intervals (CI) for pancreatic cancer risk for quartiles of marker levels adjusted for potential confounders., Results: The HR (95% CI) for the highest versus the lowest category of C-C motif ligand chemokine 8/monocyte chemoattractant protein 2 (CCL8/MCP2) was 2.03 (1.05-3.93; P trend = 0.048). After we corrected for multiple comparisons, none of the examined biomarkers were associated with pancreatic cancer risk at P -value <0.05., Conclusions: We found no significant associations between 62 inflammatory markers and pancreatic cancer risk., Impact: The suggestive association with circulating levels of leukocyte recruiting cytokine CCL8/MCP2 may warrant further investigation., (©2021 American Association for Cancer Research.)

Background: Metabolic syndrome (MetS) is a systemic inflammatory state. Low physical activity (PA) could modify this patho-physiology or act as an independent contributor to inflammation. Previous studies of both conditions have identified altered levels of inflammation- and immune-related proteins based on limited sets of candidate markers., Methods: We investigated associations of MetS and low PA with circulating inflammation markers in a stratified random sample of Japanese adults ( N = 774, mean age 60.7 years) within the Japan Public Health Center-based Prospective Study (JPHC) Cohort II. AHA/NHLBI criteria were used to define MetS (19%) and the bottom quartile of PA was considered low. 110 circulating biomarkers, including cytokines, chemokines, and soluble receptors were measured by multiplex bead-based and proximity-extension assays. Associations of MetS and low PA with marker quantiles were adjusted for each other and for age, sex, study site, cigarette smoking, alcohol consumption, and blood sample fasting state by ordinal logistic regression. P values were corrected for FDR., Results: MetS was significantly associated with levels of six markers: IL18R1 [odds ratio 2.37; 95% confidence interval (CI), 1.45-3.87], CRP (2.07; 95% CI, 1.48-2.90), SAP (2.08; 95% CI, 1.47-2.95), CCL19/MIP3β (2.06; 95% CI, 1.48-2.88), CXCL12/SDF1α+β (0.48; 95% CI, 0.32-0.65), and CCL28 (0.44; 95% CI, 0.27-0.71). Low PA had no significant marker associations., Conclusions: Positively associated markers with MetS are mostly Th1 immune response-related and acute phase proteins, whereas negatively associated markers are generally Th2-related., Impact: MetS is associated with a broad range of alterations in immune and inflammatory biomarkers that may contribute to risks of various chronic diseases, independent of low PA., (©2020 American Association for Cancer Research.)

Background: The impact of overweight duration and intensity during adulthood on the prognosis after a cancer diagnosis remains largely unknown. We investigated this association in Swedish women with breast and colorectal cancer., Methods: A cohort of 47,051 women from the Swedish Lifestyle and Health Study was included, of whom 1,241 developed postmenopausal breast (mean age at diagnosis, 57.5 years) and 259 colorectal (mean age at diagnosis, 59.1 years) cancer. Trajectories of body mass index (BMI) between ages 20 and 50 years were estimated for the full cohort using a quadratic growth model and studied in relation to risk of death from any cause using multivariate Cox regression models among cancer survivors., Results: Compared with patients with cancer who were never overweight (BMI < 25) during early adulthood (ages 20-50 years), the risk of early death from breast cancer increased by 3% [hazard ratio (HR) = 1.03; 95% confidence interval (CI), 1.01-1.05] and from colorectal cancer by 4% (HR = 1.04; 95% CI, 1.01-1.06) for every year lived with overweight. A higher intensity of overweight (i.e., a combination of duration and degree of overweight-a concept comparable to pack-years of cigarette smoking) further increased the risk of dying in this population. Although risks were slightly more pronounced for women diagnosed with late-stage breast cancer, no clear association was found for colorectal cancer., Conclusions: Our results suggest that adulthood overweight duration and intensity have a long-lasting influence on breast and colorectal cancer survival., Impact: Our study highlights the need for effective prevention of overweight and obesity starting at an early age., (©2019 American Association for Cancer Research.)

Background: Circulating inflammation proteins may be important mediators or markers of carcinogenic mechanisms. There have been few studies with limited numbers of analytes in patients with upper gastrointestinal (GI) tract tumors. We therefore evaluated risk associations of gastric and esophageal cancers with prediagnostic levels of a wide range of these molecules., Methods: We performed a case-cohort analysis within the Japan Public Health Center-Based Prospective Study Cohort II, including incident cases of gastric ( n = 446) and esophageal ( n = 68) cancers and a random subcohort ( n = 774). A total of 64 biomarkers were measured in baseline plasma using Luminex bead-based assays. The median time between blood collection and diagnosis was 8.1 years for gastric cancer and 9.4 years for esophageal cancer. HRs for association with each marker were adjusted for potential confounders using Cox regression., Results: In separate models, sEGFR and TSLP were nominally associated with gastric cancer risk, and CRP, CXCL11/ITAC, and CCL15/MIP1D were associated with esophageal cancer. However, no association satisfied statistical significance after FDR correction. Associations did not differ by time from blood collection to cancer (<5 vs. ≥5 years)., Conclusions: Our study failed to identify associations of circulating inflammation markers with risk of upper GI tract tumors., Impact: To date, this is the largest assessment of inflammation-related proteins with gastric and esophageal cancer risks. However, the evaluated molecules may not fully represent the complex inflammation processes preceding malignant transformation. Further investigation of other markers in prospective studies is warranted, as demonstration of associations may have important implications for prevention and treatment of these cancers., (©2019 American Association for Cancer Research.)