Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer

• Published in: British journal of cancer Vol. 115; no. 2; pp. 266 - 272
• Main Authors: Jarvis, David, Mitchell, Jonathan S, Law, Philip J, Palin, Kimmo, Tuupanen, Sari, Gylfe, Alexandra, Hänninen, Ulrika A, Cajuso, Tatiana, Tanskanen, Tomas, Kondelin, Johanna, Kaasinen, Eevi, Sarin, Antti-Pekka, Kaprio, Jaakko, Eriksson, Johan G, Rissanen, Harri, Knekt, Paul, Pukkala, Eero, Jousilahti, Pekka, Salomaa, Veikko, Ripatti, Samuli, Palotie, Aarno, Järvinen, Heikki, Renkonen-Sinisalo, Laura, Lepistö, Anna, Böhm, Jan, Meklin, Jukka-Pekka, Al-Tassan, Nada A, Palles, Claire, Martin, Lynn, Barclay, Ella, Farrington, Susan M, Timofeeva, Maria N, Meyer, Brian F, Wakil, Salma M, Campbell, Harry, Smith, Christopher G, Idziaszczyk, Shelley, Maughan, Timothy S, Kaplan, Richard, Kerr, Rachel, Kerr, David, Buchanan, Daniel D, Win, Aung K, Hopper, John L, Jenkins, Mark A, Lindor, Noralane M, Newcomb, Polly A, Gallinger, Steve, Conti, David, Schumacher, Fred, Casey, Graham, Taipale, Jussi, Aaltonen, Lauri A, Cheadle, Jeremy P, Dunlop, Malcolm G, Tomlinson, Ian P, Houlston, Richard S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.07.2016; Nature Publishing Group
• Subjects: 692/499; 692/699/67/1504/1885; 692/699/67/68; 692/700/139/2818; Adiposity - genetics; Adult; Biomedical and Life Sciences; Biomedicine; Birth weight; Body mass index; Cancer Research; Colorectal cancer; Colorectal Neoplasms - complications; Colorectal Neoplasms - genetics; Confounding (Statistics); Drug Resistance; Epidemiology; Female; Genetics and Genomics; Genome-Wide Association Study; Genomes; Humans; Lifestyles; Male; Medicin och hälsovetenskap; Middle Aged; Molecular Medicine; Obesity; Observational studies; Oncology; Polymorphism, Single Nucleotide; Random Allocation; Weight control; adiposity; Mendelian randomisation; colorectal cancer
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/bjc.2016.188

Background: Observational studies have associated adiposity with an increased risk of colorectal cancer (CRC). However, such studies do not establish a causal relationship. To minimise bias from confounding we performed a Mendelian randomisation (MR) analysis to examine the relationship between adiposity and CRC. Methods: We used SNPs associated with adult body mass index (BMI), waist-hip ratio (WHR), childhood obesity and birth weight as instrumental variables in a MR analysis of 9254 CRC cases and 18 386 controls. Results: In the MR analysis, the odds ratios (ORs) of CRC risk per unit increase in BMI, WHR and childhood obesity were 1.23 (95% CI: 1.02–1.49, P =0.033), 1.59 (95% CI: 1.08–2.34, P =0.019) and 1.07 (95% CI: 1.03–1.13, P =0.018), respectively. There was no evidence for association between birth weight and CRC (OR=1.22, 95% CI: 0.89–1.67, P =0.22). Combining these data with a concurrent MR-based analysis for BMI and WHR with CRC risk (totalling to 18 190 cases, 27 617 controls) provided increased support, ORs for BMI and WHR were 1.26 (95% CI: 1.10–1.44, P =7.7 × 10 −4 ) and 1.40 (95% CI: 1.14–1.72, P =1.2 × 10 −3 ), respectively. Conclusions: These data provide further evidence for a strong causal relationship between adiposity and the risk of developing CRC highlighting the urgent need for prevention and treatment of adiposity.