Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer.
Henry Rodriguez-BroadbentPhilip J LawAmit SudKimmo PalinSari TuupanenAlexandra GylfeUlrika A HänninenTatiana CajusoTomas TanskanenJohanna KondelinEevi KaasinenAntti-Pekka SarinSamuli RipattiJohan G ErikssonHarri RissanenPaul KnektEero PukkalaPekka JousilahtiVeikko SalomaaAarno PalotieLaura Renkonen-SinisaloAnna LepistöJan BöhmJukka-Pekka MecklinNada A Al-TassanClaire PallesLynn MartinElla BarclaySusan M FarringtonMaria N TimofeevaBrian F MeyerSalma M WakilHarry CampbellChristopher G SmithShelley IdziaszczykTimothy S MaughanRichard KaplanRachel KerrDavid KerrMichael N PassarelliJane C FigueiredoDaniel D BuchananAung-Ko WinJohn L HopperMark A JenkinsNoralane M LindorPolly A NewcombSteven GallingerDavid ContiFred SchumacherGraham CaseyLauri A AaltonenJeremy P CheadleIan P TomlinsonMalcolm G DunlopRichard S HoulstonPublished in: International journal of cancer (2017)
While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP-CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20-1.79, p = 1.68 × 10-4 ). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92-1.18, p = 0.49), 0.94 (95% CI: 0.84-1.05, p = 0.27), and 0.98 (95% CI: 0.85-1.12, p = 0.75) respectively. A genetic risk score for 3-hydoxy-3-methylglutaryl-coenzyme A reductase (HMGCR) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR = 0.69, 95% CI: 0.49-0.99, p = 0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia.