Genetic risk, incident colorectal cancer, and the benefits of adhering to a healthy lifestyle: A prospective study using data from UK Biobank and FinnGen

Abstract

BackgroundGenetic factors increase the individual risk of colorectal cancer (CRC); however, the extent to which a healthy lifestyle can offset increased genetic risk is unknown. This study investigated whether a healthy lifestyle is associated with lower CRC risk, regardless of genetic risk.MethodsWe recruited 390,365 participants without cancer at baseline (2006–2010) from the UK Biobank. The primary outcome was CRC incidence. A healthy lifestyle score constructed using 16 factors of six dimensions (smoking, drinking, body mass index, diet, exercise, and sleep) was categorized into three risk categories: favorable, intermediate, and unfavorable. To calculate the polygenic risk scores (PRSs) of UK Biobank participants, we extracted 454,678 single nucleotide polymorphisms (SNPs) from the UK Biobank and FinnGen Biobank after quality control. Cox proportional hazards regression was performed to evaluate the associations and was expressed as hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsDuring a median follow-up of 10.90 years, 4,090 new CRC cases were reported in the UK Biobank. The “best-fit” PRSs were constructed using 59 SNPs based on the UK Biobank cohort and FinnGen genome-wide association study summary data (R2 = 0.23%) and were divided into low (lowest quintile), intermediate (including second–fourth quintile), and high (highest quintile) genetic risk categories. The multivariate-adjusted Cox model revealed that participants with favorable lifestyles had HRs of 0.66 (95% CI = 0.60–0.72) for developing CRC vs. those with unfavorable lifestyles; low genetic risk was associated with a decreased risk of CRC (HR = 0.67, 95% CI =0.61–0.74) compared with those with high genetic risk. The HRs for low genetic risk participants with favorable lifestyles were 0.44 (95% CI =0.36–0.55) vs. participants with high genetic risk and unfavorable lifestyles. Among the participants with low, intermediate, or high genetic risk, the HRs of favorable vs. unfavorable lifestyles were 0.74, 0.64, and 0.72 (all p< 0.05).ConclusionsLow genetic risk and a favorable lifestyle were significantly associated with a decreased risk of CRC. A favorable lifestyle was associated with a lower CRC risk, regardless of genetic risk.

Associations of Diet with Health Outcomes in the UK Biobank: A Systematic Review

“…Dietary data were collected using the FFQ during the initial assessment visit (2006–2010). Several studies have utilised UK Biobank dietary data from the FFQ to find an association of disease risk not only with individual food types [ 19 , 21 , 24 , 26 , 28 , 39 , 41 , 42 , 44 ], but also with dietary patterns [ 13 , 29 , 31 ] and dietary indices [ 16 , 17 , 30 , 35 , 37 , 40 ].…”

“…This result is similar to those reported by the European Prospective Investigation into Cancer and Nutrition (EPIC) [ 55 ]. However, the results obtained by Wu et al [ 30 ] suggest that genetics may be more important than diet in preventing colorectal cancer, as they observed a lower hazard ratio (HR) of 0.44 for low genetic risk and favourable lifestyle, compared to 0.73 for high genetic risk and favourable lifestyle, and 0.92 for healthy diet alone.…”

“…Moreover, some diet types that limit or exclude meat consumption (such as fish eaters and vegetarians) showed a beneficial effect on lowering cancer risk [29]. Studies that followed a healthy diet (with adequate fruits, vegetables, fish, and whole grains, and limited processed and red meats and refined grains) also observed a lower colorectal cancer risk [29,30]. This result is similar to those reported by the European Prospective Investigation into Cancer and Nutrition When the basis of association is on a single food group or macronutrient, the outcome can be different for the same type of food.…”

High polygenic risk score is a risk factor associated with colorectal cancer based on data from the UK Biobank

“…Studies also evaluated whether a healthy lifestyle can offset increased genetic risk in CRC [ 39 , 40 ]. Healthy lifestyle scores were constructed using numbers of lifestyle factors, and were categorized into unhealthy (unfavorable), intermediate, and healthy (favorable) groups.…”