Genetic risk, metabolic syndrome, and gastrointestinal cancer risk: A prospective cohort study

Abstract

Background Gastrointestinal (GI) cancer risk has been associated with metabolic syndrome (MetS), a surrogate indicator for unhealthy lifestyles, and a number of genetic loci, but the combined effect of MetS and genetic variants on GI cancer risk is uncertain. Methods We included 430,036 participants with available MetS and genotype data from UK Biobank. During the follow‐up time, 5494 incident GI cancer cases, including esophageal cancer, gastric cancer, and colorectal cancer, were identified. We created a GI polygenic risk score (GI‐PRS) for overall GI cancer derived from three site‐specific cancer PRSs. Cox proportional hazards regression was used to estimate the associations of MetS and GI‐PRS with the risk of GI cancer. Results MetS was significantly associated with 28% increment in GI cancer risk (hazard ratio [HR] MetS vs. non‐MetS : 1.28, 95% confidence interval [CI]: 1.21–1.35, p < 0.0001), whereas a high GI‐PRS (top quintile) was associated with 2.28‐fold increase in risk (HR high vs. low : 2.28, 95% CI: 2.09–2.49, p < 0.0001). Compared with participants without MetS and at low genetic risk (bottom quintile of GI‐PRS), those with MetS and at high genetic risk had 2.75‐fold increase in GI cancer risk (HR: 2.75, 95% CI: 2.43–3.12, p < 0.0001). Additionally, MetS in comparison with no MetS had 1.49‰, 2.75‰, and 3.37‰ absolute risk increases in 5 years among participants at low, intermediate (quintiles 2–4 of GI‐PRS) and high genetic risk, respectively, representing the number of subjects diagnosed as MetS causing a new GI cancer case in 5 years were 669, 364, and 296, respectively. Conclusions Metabolic and genetic factors may jointly contribute to GI cancer risk and may serve as predictors by quantitative measurements to identify high‐risk populations of GI cancer for precise prevention.

Association of a Healthy Lifestyle with All-Cause, Cause-Specific Mortality and Incident Cancer among Individuals with Metabolic Syndrome: A Prospective Cohort Study in UK Biobank

“…Nearly one-fifth of deaths among populations with MetS could be attributed to nonadherence to six to seven recommended lifestyle behaviours. Notably, the contributing beneficial effect of adherence to six to seven health lifestyle behaviours to respiratory and digestive diseases is better than cancer and CVD diseases, possibly due to the other diseases, such as cancer, are more susceptible to genetic or other lifestyle factors [ 17 ]. Meanwhile, when participants with MetS had a favourable lifestyle, the risk of developing overall cancer incidence and site-specific cancer incidence in the digestive organs, breast, respiratory, and intrathoracic organs was reduced.…”

“…Research on all-cause and cause-specific mortality and the overall incidence of cancer are limited. Given the high mortality and cancer risk in individuals with MetS [ 5 , 17 ], it is critical to investigate the potential of modifiable lifestyles to prevent death and cancer incidence in individuals with MetS.…”

Healthy Diet, Polygenic Risk Score, and Upper Gastrointestinal Cancer Risk: A Prospective Study from UK Biobank

“…Then, we built a UGI-PRS to assess UGI cancer risk by summing site-specific PRSs weighted by ESC and GC age-standardized incidence rate in the UK population [ 35 ]. Cancer site-specific PRS has been proven to effectively identify individuals with high risk of overall cancers and gastrointestinal cancer risk [ 36 , 37 ]. The UGI-PRS was divided into three levels of genetic risk: low (lowest quintile), moderate (quintiles 2–4), and high (top quintile).…”

Metabolisches Syndrom und gastrointestinale Krebsvorsorge

“…beim HDL-Cholesterin ein zu niedriger Wert vor oder werden bereits Medikamente zur Normalisierung dieser Werte eingenommen, spricht man vom metabolischen Syndrom. MetS-Patienten haben ein erhöhtes Risiko, an Adenokarzinomen von Speiseröhre, Magen, Bauchspeicheldrüse, Leber, Gallenwegen und Darm zu erkranken und daran zu versterben [4,5,6,7,8,9,10,11]. Je mehr Komponenten des MetS jemand hat, desto stärker steigt sein spezifisches Krebsrisiko [5,12,13,14,15].…”