Abstract

Simple SummaryMost colorectal cancers assumedly develop from precursor lesions, i.e., colorectal adenomas (adenoma-carcinoma sequence). Epidemiological and clinical data supporting this hypothesis are limited. Therefore, the aim of the present study was to estimate relative dynamics of colorectal adenoma-carcinoma sequence for groups of screenees stratified by body mass. We have analyzed 163,129 individuals that underwent screening colonoscopy and calculated adjusted prevalences of colorectal adenomas and colorectal. Based on that data we have found that obese individuals are more likely to develop adenomas, advanced adenomas and early CRC but less likely to progress to advanced CRC. Therefore, this study provides new evidence that obesity paradox exists for colorectal cancer. Most colorectal cancers (CRC) assumedly develop from precursor lesions, i.e., colorectal adenomas (adenoma-carcinoma sequence). Epidemiological and clinical data supporting this hypothesis are limited. Therefore, the aim of the present study is to estimate relative dynamics of colorectal adenoma-carcinoma sequence for groups of screenees stratified by BMI (body mass index) based on prevalence data from Polish Colonoscopy Screening Program (PCSP). We performed a cross-sectional analysis of database records of individuals who entered the national opportunistic colonoscopy screening program for CRC in Poland. We calculated prevalence of adenomas and CRCs adjusted for sex, 5-year age group, family history of CRC, smoking, diabetes and use of aspirin, hormonal therapy and proton-pump inhibitors use. Thereafter we calculated estimated transition rate (eTR) with confidence intervals (CIs) defined as adjusted prevalence of more advanced lesion divided by adjusted prevalence of less advanced lesion. All analyzes were stratified according to the BMI categories: normal (BMI 18.0 to <25.0), overweight (BMI 25.0 to <30.0) and obese (BMI ≥ 30.0). Results are reported in the same respective order. After exclusions we performed analyses on 147,385 individuals. We found that prevalence of non-advanced adenomas is increasing with BMI category (12.19%, 13.81%, 14.70%, respectively; p < 0.001). Prevalence of advanced adenomas was increasing with BMI category (5.20%, 5.77%, 6.61%, respectively; p < 0.001). Early CRCs prevalence was the highest for obese individuals (0.55%) and the lowest for overweight individuals (0.44%) with borderline significance (p = 0.055). For advanced CRC we found that prevalence seems to be inversely related to BMI category, however no statistically significant differences were observed (0.35%, 0.31%, 0.28%; p = 0.274). eTR for non-advanced adenoma to advanced adenoma is higher for obese individuals than for overweight individuals with bordering CIs (42.65% vs. 41.81% vs. 44.95%) eTR for advanced adenoma to early CRC is highest for normal individuals, however CIs are overlapping with remaining BMI categories (9.02% vs. 7.67% vs. 8.39%). eTR for early CRC to advanced CRC is lower for obese individuals in comparison to both normal and overweight individuals with marginally overlapping CIs (73.73% vs. 69.90% vs. 50.54%). Obese individuals are more likely to develop adenomas, advanced adenomas and early CRC but less likely to progress to advanced CRC. Therefore, this study provides new evidence that obesity paradox exists for colorectal cancer.

Highlights

  • An acclaimed paradigm states that most colorectal cancers (CRC) develop from precursor lesions, i.e., colorectal adenomas (CRA) [1]

  • Obese individuals are more likely to develop adenomas, advanced adenomas and early CRC but less likely to progress to advanced CRC

  • The aim of the present study is to estimate relative dynamics of colorectal adenoma-carcinoma sequence for groups of screenees stratified by BMI based on prevalence data on asymptomatic individuals screened within Polish Colonoscopy Screening Program (PCSP)

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Summary

Introduction

An acclaimed paradigm states that most CRCs develop from precursor lesions, i.e., colorectal adenomas (CRA) [1]. Researchers attempted to assess epidemiology of abovementioned lesions with use of post mortem examinations [4,5,6,7] It is known, that not all CRAs will progress to CRC. It is crucial to assess the probability of that progression as well as to identify lesions that are at the greatest risk of progression and estimate the time of that progression To date this has been only partially accomplished, to some extent due to study design difficulties. Such design enables assessment of prevalence of lesions found in the screened population, what can be used to observe the dynamic of cancer development Facilitating such methodology to analyze adenoma-carcinoma sequence in CRC may benefit the current state of knowledge, especially given the substantial numbers of individuals undergoing screening

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