title: The mTOR Pathway and the Role of Energy Balance Throughout Life in Colorectal Cancer Etiology and Prognosis: Unravelling Mechanisms Through a Multidimensional Molecular Epidemiologic Approach.
abstract: Timing of exposure to lifestyle factors that influence energy balance may differentially affect colorectal cancer (CRC) risk and prognosis. Caloric restriction in youth and short stature, as markers of early-life exposures, have shown to decrease CRC risk, whereas large body size and low physical activity levels in adulthood are established risk factors for CRC. Regarding prognosis, overweight, sarcopenia, and their co-occurrence (sarcopenic obesity) may negatively influence the health and quality of life of CRC survivors. There is mechanistic support for disruption of the mammalian target of rapamycin (mTOR) pathway as an underlying mechanism possibly driving these associations, because mTOR integrates signals from growth factors, nutrients, mutagens, and hormones to induce cell proliferation, resistance to apoptosis, and autophagy. However, epidemiologic evidence connecting mTOR to energy-balance-related CRC throughout the lifespan is scarce. This perspective proposes how multidimensional molecular epidemiologic studies can shed light on the etiology and prognosis of energy-balance-related CRC.
authors: Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, P.O. Box 616, Maastricht, 6200 MD The Netherlands.
authors: Matty P
authors: MP
authors: Weijenberg
authors: Laura A E
authors: LA
authors: Hughes
authors: Martijn J L
authors: MJ
authors: Bours
authors: Colinda C J M
authors: CC
authors: Simons
authors: Manon
authors: M
authors: van Engeland
authors: Piet A
authors: PA
authors: van den Brandt
keywords: Adolescent; Biomarkers; Cancer prognosis; Cancer risk; Cancer survivor; Childhood; Colon; Diet; Dietary protein; Elderly; Energy balance; Energy restriction; Epigenetic; Etiology; Genetic variation; Gut microbiota; Immunohistochemical expression; Molecular epidemiology; Neoplasm; Obesity; Overweight; Physical activity; Rectum; Sarcopenia; Somatic mutations; mTOR pathway
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