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Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development., (© 2024. The Author(s).)

Background: Recent studies have shown that some four in ten cancers are attributable to a few key risk factors. The aim of this study was to estimate cohort-based population attributable fractions (PAFs) in Finland for potentially modifiable cancer risk factors., Methods: Data from eight health studies including 253,953 subjects with 29,802 incident malignant solid tumors were analysed using Bayesian multivariate regression model with multiplicative risk factor effects. We estimated the effects of smoking, excess body weight, alcohol consumption, physical activity, parity and education on cancer incidence and related PAFs by cancer site, accounting for competing mortality., Results: PAF for all cancer sites and exposures combined was 34% (95% credible interval 29%-39%) in men and 24% (19%-28%) in women. In men, 23% (21%-27%) and in women 8% (6%-9%) of all cancers were attributed to smoking. PAF related to excess body weight was 4% (2%-6%) in men and 5% (2%-7%) in women, to alcohol 7% (3%-10%) in men and 4% (0%-7%) in women, and to excess body weight and alcohol combined 10% (6%-15%) in men and 9% (4%-13%) in women., Conclusion: Smoking was the most important factor contributing to cancer burden in Finnish men and women over the last 40 years. The contribution of excess body weight and alcohol consumption together outweighed the role of smoking in women. As the prevalence of overweight is expected to increase, more efficient public health measures supporting adherence to healthy weight are essential to reduce cancer burden., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The prevalence of coeliac disease doubled in Finland from 1980 to 2000., Aims: To investigate whether this increase is continuing and if there are specific patient-related factors predicting the development of coeliac disease at a population level., Methods: We elicited comprehensive health data in the nationwide Health 2000 and Health 2011 surveys. Serum samples were taken for the measurement of tissue transglutaminase antibodies (TGA); subjects who were seropositive were tested for endomysial antibodies (EmA). Coeliac disease was defined either as a reported diagnosis or as positive TGA and EmA. The surveys comprised, respectively, 6379 and 4056 individuals, forming representative samples for 2,946,057 and 2,079,438 Finnish adults. Altogether 3254 individuals participating in both surveys comprised a prospective follow-up cohort., Results: Prevalence of coeliac disease was 2.12% in 2000 and 2.40% in 2011 (p = 0.156). In the prospective cohort, 16 out of the 3254 (0.49%) subjects developed coeliac disease during follow-up from 2000 to 2011, with an annual incidence rate of 45 per 100,000 persons. Positive TGA without EmA (OR: 133, 95% CI: 30.3-584), TGA values in the upper normal range (51.1, 16.0-163), and after adjusting for TGA, previous autoimmune co-morbidity (8.39, 4.98-35.9) in 2000 increased the likelihood of subsequent coeliac disease., Conclusions: The nationwide prevalence of coeliac disease kept on rising from 2.12% in 2000 to 2.40% in 2011 in Finland. Positive TGA without EmA, TGA titres in the upper normal range and a pre-existing autoimmune disease predisposed to coeliac disease during the 10-year follow-up., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)