Decoding the Link Between Body Shapes and Colorectal Cancer Risk: Groundbreaking Insights Revealed

In a groundbreaking study published in Science Advances, researchers unveiled novel insights into the relationship between body shape phenotypes and the risk of colorectal cancer (CRC), offering a fresh perspective on the distinct molecular pathways involved. The study led by Laia Peruchet-Noray from the International Agency for Research on Cancer (IARC/WHO) and colleagues, utilized a comprehensive approach combining an observational analysis, genome-wide association studies (GWAS), and Mendelian randomization (MR) analyses.

The study analyzed 329,828 participants from the UK Biobank, identifying 3,728 CRC cases during the follow-up period. Researchers derived four distinct multi-trait body shape phenotypes based on BMI, height, weight, waist-to-hip ratio, and waist and hip circumference using principal components analysis. They found that two particular body shapes - a generally obese body shape and a tall, centrally obese body shape - were both significantly associated with increased CRC risk.

Moving beyond observational analysis, the researchers conducted GWAS in a larger group of 460,198 UK Biobank participants, discovering 3,414 genetic variants across the four body shapes. Notably, 570 of these variants were novel in relation to anthropometric traits. The MR analysis further confirmed the positive associations of the generally obese and tall, centrally obese phenotypes with CRC risk, utilizing data from large CRC genetic consortia including 52,775 cases and 45,940 controls.

The study's tissue expression enrichment analysis revealed that the genetic instruments for the generally obese body shape were predominantly related to brain tissue, highlighting a potential neural regulation of obesity and its link to CRC. Conversely, the tall, centrally obese body shape was primarily driven by adipose tissue–specific genetic instruments, emphasizing distinct putative causal pathways between adiposity subtypes and CRC.

The findings from this multi-faceted study underscore the complexity of the obesity-CRC relationship and highlight the importance of considering specific body shapes in cancer risk assessments. By identifying molecular targets for intervention, the research might further our understanding of obesity’s contribution to CRC and open new avenues for prevention and treatment.

This study, titled "Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer," was conducted by a team of international researchers, with its copyright © 2024 held by the authors and a Creative Commons Attribution NonCommercial License (CC BY-NC) applied. The full text is available at Science.org and was accessed on April 25, 2024.

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