Is the association of overweight and obesity with colorectal cancer underestimated? An umbrella review of systematic reviews and meta-analyses

Abstract

Although high body-mass index (BMI) is associated with increased risk of developing colorectal cancer (CRC), many CRC patients lose weight before diagnosis. BMI is often reported close to diagnosis, which may have led to underestimation or even reversal of direction of the BMI-CRC association. We aimed to assess if and to what extent potential bias from prediagnostic weight loss has been considered in available epidemiological evidence. We searched PubMed and Web of Science until May 2022 for systematic reviews and meta-analyses investigating the BMI-CRC association. Information on design aspects and results was extracted, including if and how the reviews handled prediagnostic weight loss as a potential source of bias. Additionally, we analyzed how individual cohort studies included in the latest systematic review handled the issue. Overall, 18 reviews were identified. None of them thoroughly considered or discussed prediagnostic weight loss as a potential source of bias. The majority (15/21) of cohorts included in the latest review did not exclude any initial years of follow-up from their main analysis. Although the majority of studies reported having conducted sensitivity analyses in which initial years of follow-up were excluded, results were reported very heterogeneously and mostly for additional exclusions of 1–2 years only. Where explicitly reported, effect estimates mostly increased with increasing length of exclusion. The impact of overweight and obesity on CRC risk may be larger than suggested by the existing epidemiological evidence.

Association of Overweight, Obesity, and Recent Weight Loss With Colorectal Cancer Risk

“…These values are close to the estimates we obtained when looking at weight 0 to 2 years before diagnosis or interview in our case-control study, but considerably lower than the estimates obtained when looking at weight a longer time ago. However, a closer look at the individual primary studies included in this meta-analysis revealed that the majority of those studies (15 of 21) did not exclude any initial years of follow-up, and 9 out of 20 studies reporting on obesity had relatively short follow-up times (less than 10 years) . Those that did exclude some first years of follow-up in their sensitivity analyses, did so mostly only for the first 1 or 2 years, and have rarely explicitly reported results from such analyses.…”

“…However, a closer look at the individual primary studies included in this meta-analysis revealed that the majority of those studies (15 of 21) did not exclude any initial years of follow-up, and 9 out of 20 studies reporting on obesity had relatively short follow-up times (less than 10 years). 13 Those that did exclude some first years of follow-up in their sensitivity analyses, did so mostly only for the first 1 or 2 years, and have rarely explicitly reported results from such analyses. Our findings suggest that more rigorous approaches may be needed to fully disclose the association of excess weight with CRC risk, which may be substantially larger than previously assumed.…”

“…Most studies have ascertained body weight at a single point in time, usually close to the time of cancer diagnosis (case-control studies) or participant enrollment (cohort studies), ie, at the time when cancer-associated weight loss may already have occurred. Furthermore, in a 2023 umbrella review, we have shown that none of the previous 18 reviews looking at the BMI-CRC association considered prediagnostic weight loss as a potential source of bias. This may have led to an underestimation of the association of overweight and obesity with CRC risk in epidemiological studies, but the magnitude of such underestimation is unknown.…”

Ultra-processed food consumption and metabolic disease risk: an umbrella review of systematic reviews with meta-analyses of observational studies

“…), 95% confidence interval (CI), and the number of cases or total population; and (4) studies that included less than three original studies. When more than one meta-analysis on the same association was eligible, only the latest meta-analysis was included ( 29 ). Of note, any comparison of exposure could be included and treated as a unique meta-analysis, such as highest/moderate vs. lowest, and dose–response analysis ( 30–32 ).…”

Single-cell transcriptome analysis reveals immunosuppressive landscape in overweight and obese colorectal cancer

“…The Global Cancer Burden Report shows that the global incidence of CRC ranked third among malignant tumors in 2020 [ 1 ]. Extensive epidemiological and clinical studies have provided evidence that overweight and obesity is a risk factor for developing CRC [ 2 ]. While there is growing evidence indicating a link between overweight, obesity, and CRC, the precise molecular mechanisms underlying this association are still not fully understood [ 3 ].…”