Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer.
Jarvis D., Mitchell JS., Law PJ., Palin K., Tuupanen S., Gylfe A., Hänninen UA., Cajuso T., Tanskanen T., Kondelin J., Kaasinen E., Sarin A-P., Kaprio J., Eriksson JG., Rissanen H., Knekt P., Pukkala E., Jousilahti P., Salomaa V., Ripatti S., Palotie A., Järvinen H., Renkonen-Sinisalo L., Lepistö A., Böhm J., Meklin J-P., Al-Tassan NA., Palles C., Martin L., Barclay E., Farrington SM., Timofeeva MN., Meyer BF., Wakil SM., Campbell H., Smith CG., Idziaszczyk S., Maughan TS., Kaplan R., Kerr R., Kerr D., Buchanan DD., Win AK., Hopper JL., Jenkins MA., Lindor NM., Newcomb PA., Gallinger S., Conti D., Schumacher F., Casey G., Taipale J., Aaltonen LA., Cheadle JP., Dunlop MG., Tomlinson IP., Houlston RS.
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.