Combined effect of modifiable and non-modifiable risk factors for colorectal cancer risk in a pooled analysis of 11 population-based studies

Abstract

Objective‘Environmental’ factors associated with colorectal cancer (CRC) risk include modifiable and non-modifiable variables. Whether those with different non-modifiable baseline risks will benefit similarly from reducing their modifiable CRC risks remains unclear.DesignUsing 7945 cases and 8893 controls from 11 population-based studies, we combined 17 risk factors to characterise the overall environmental predisposition to CRC (environmental risk score (E-score)). We estimated the absolute risks (ARs) of CRC of 10 and 30 years across E-score using incidence-rate data from the Surveillance, Epidemiology, and End Results programme. We then combined the modifiable risk factors and estimated ARs across the modifiable risk score, stratified by non-modifiable risk profile based on genetic predisposition, family history and height.ResultsHigher E-score was associated with increased CRC risk (ORquartile, 1.33; 95% CI 1.30 to 1.37). Across E-scores, 30-year ARs of CRC increased from 2.5% in the lowest quartile (Q1) to 5.9% in the highest (Q4) quartile for men, and from 2.1% to 4.5% for women. The modifiable risk score had a stronger association in those with high non-modifiable risk (relative excess risk due to interaction=1.2, 95% CI 0.5 to 1.9). For those in Q4 of non-modifiable risk, a decrease in modifiable risk reduced 30-year ARs from 8.9% to 3.4% for men and from 6.0% to 3.2% for women, a level lower or comparable to the average population risk.ConclusionsChanges in modifiable risk factors may result in a substantial decline in CRC risk in both sexes. Those with high inherited risk may reap greater benefit from lifestyle modifications. Our results suggested comprehensive evaluation of environmental factors may facilitate CRC risk stratification.

Nongenetic Determinants of Risk for Early-Onset Colorectal Cancer

“…Our study, including 3767 early-onset CRC and 4049 controls, demonstrated that several nongenetic factors known to be involved in late-onset CRC ( 27 , 37 ) are also relevant for early-onset disease. In particular, not regularly using NSAIDs, greater red meat intake, alcohol abstinence and heavier alcohol use, and lower educational attainment were statistically significantly associated with early-onset CRC.…”

“…For studies that assessed height and BMI via direct measurement, variables were captured at the reference time of each respective study. To ensure comparability of variables across studies, all data underwent a multiphase, iterative harmonization process (see the Supplementary Methods , available online) ( 27 , 37 ). Briefly, variables were grouped into a single dataset with universal definitions, standardized coding, and acceptable values.…”

“…All dietary variables were modeled as sex- and study-specific quartiles. For all variables, the referent level was the category linked to the lowest risk for CRC based on previously published studies such that the effect estimates for each factor would represent an increase in CRC risk ( 27 , 37 ). Family history of CRC was defined as having 1 or more first-degree relatives with CRC.…”

Distinctive Clinico-Pathological Characteristics of Colorectal Cancer in Sabahan Indigenous Populations

“…This study revealed that indigenous patients were three times more likely to get CRC at an earlier age compared to the Chinese patients, and this could be attributed by the interaction of multiple established risk factors associated with colorectal cancer, namely the modifiable and non-modifiable risks, thus leading to an earlier occurrence of CRC within this group (Wang et al, 2019;Jamal et al, 2020). An epidemiological study in the near future could help identify these risk factors and hence improve the community awareness towards this disease, leading to earlier screening for non-modifiable risks and avoidance of certain the modifiable risks (Wang et al, 2019). Having said that, an epidemiological study to identify risk factors could be costly and tedious, unless there is an international collaboration pertaining to assessing these risk factors in the indigenous population globally.…”

“…Instead, it would be more helpful if the cost is used to start a national screening programme for CRC with an emphasis for earlier screening in the indigenous population . Furthermore, risk stratification tools also can be used to aid screening programme by identifying high risk individuals amongst the indigenous population (Wang et al, 2019).…”