Abstract
Colorectal cancer (CRC) is the third most common cancer in economically developed countries and a major cause of cancer-related mortality. The importance of lifestyle and diet as major determinants of CRC risk is suggested by differences in CRC incidence between countries and in migration studies. Previous observational epidemiological studies have identified associations between modifiable environmental risk factors and CRC, but these studies can be susceptible to reverse causation and confounding, and their results can therefore conflict. Mendelian randomisation (MR) analysis represents an approach complementary to conventional observational studies examining associations between exposures and disease. The MR strategy employs allelic variants as instrumental variables (IVs), which act as proxies for non-genetic exposures. These allelic variants are randomly assigned during meiosis and can therefore inform on life-long exposure, whilst not being subject to reverse causation. In previous studies MR frameworks have associated several modifiable factors with CRC risk, including adiposity, hyperlipidaemia, fatty acid profile and alcohol consumption. In this review we detail the use of MR to investigate and discover CRC risk factors, and its future applications.
Highlights
Colorectal cancer (CRC) is one of the most common cancers in economically developed countries and a major cause of cancer-related mortality (Forman et al, 2014)
Given the importance of these factors in CRC risk, the modification of lifestyle and diet through public health initiatives offers the prospect of significant impact on CRC incidence
To reduce CRC incidence through public health initiatives, it is imperative to determine which factors associated with CRC risk are causally related, and which are correlated
Summary
Colorectal cancer (CRC) is one of the most common cancers in economically developed countries and a major cause of cancer-related mortality (Forman et al, 2014). The disease is currently diagnosed in over one million individuals worldwide annually; its incidence is set to rise in developing countries with the adoption of western lifestyles and diets (Haggar and Boushey, 2009). The importance of lifestyle and diet as major determinants of CRC risk have been strongly suggested by geographical differences in CRC incidence and demonstrated in migration studies (Kamangar et al, 2006). Given the importance of these factors in CRC risk, the modification of lifestyle and diet through public health initiatives offers the prospect of significant impact on CRC incidence. The full compendium of exposures affecting CRC risk, and their relative contributions, has yet to be elucidated necessitating further work to discover and validate risk factors
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