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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; Ptrend = 0.048). After we corrected for multiple comparisons, none of the examined biomarkers were associated with pancreatic cancer risk at P-value 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.

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.

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 ( 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.

Purpose: Alcohol use is causally linked to multiple cancer sites. We present global, regional and national estimates of alcohol-attributable cancer burden in 2020 to inform alcohol policy and cancer control across different settings globally. Methods: In this population-based study, we calculated population attributable fractions (PAFs) using relative risk estimates and alcohol use prevalence by age, sex, and country. Assuming a 10-year latency period between alcohol consumption and cancer occurrence, we used alcohol consumption prevalence from 2010 and GLOBOCAN 2020 data to estimate new cancer cases attributable to alcohol consumption. We also calculated the contribution of moderate (60 g per day) drinking to the total alcohol-attributable cancer burden. Results: Globally, an estimated 702 900, or 3.9%, of all new cases of cancer in 2020 were attributable to alcohol consumption. Males represented 71.1% of the total alcohol-attributable cancer cases. The cancer sites which contributed the most alcohol-attributable cases were cancers of the esophagus (183 000 cases), liver (142 600 cases), and breast (114 300 cases). PAFs were lowest in Northern Africa and Western Asia (less than 1%) in both sexes, and highest in Eastern Asia (7.7%) and Central and Eastern Europe (6.9%) in men, and in Central and Eastern Europe (3.8%), Western Europe (3.5%) and Australia and New Zealand (3.55%) in women. Risky and heavy drinking contributed most to the burden of alcohol-attributable cancers (42.6% and 42.5%, respectively), and moderate drinking contributed 14.9%. Conclusion: Our findings highlight the need for effective policy and interventions to increase awareness of cancer risks associated with alcohol use and decrease overall alcohol consumption to avoid future rises in alcohol-attributable cancer burden in several regions of the world. Citation Format: Harriet Rumgay, Kevin Shield, Hadrien Charvat, Pietro Ferrari, Bundit Sornpaisarn, Isidore Obot, Farhad Islami, Valery Lemmens, Jürgen Rehm, Isabelle Soerjomataram. Global Burden of Cancer in 2020 Attributable to Alcohol Consumption: A Population-Based Study [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 43.