Abstract

BackgroundSidedness (right/left) of colorectal cancer (CRC) is essential for treatment. Whether carcinogenesis of tobacco varies by sidedness remains unclear. The present study aims to evaluate the sidedness tendency of cigarette smoking and to explore its impact on prognosis.MethodsIn the multi-center retrospective study, data on 46 166 Chinese CRC patients were extracted from a big-data platform. Logistic regression analyses were performed to evaluate qualitative and quantitative associations between smoking and tumor sidedness. Survival analyses were conducted in metastatic CRC.ResultsHistory of smoking was associated with left-sided CRC (LSCRC; Adjusted odds ratio, 1.25; 95% CI, 1.16 − 1.34; P < .001). The sidedness tendency towards LSCRC increased from non-smokers, to ex-smokers, and to current smokers (P for trend < .001). Longer duration (P for trend < .001) and larger total amount of cigarette smoking (P for trend < .001) were more associated with LSCRC, respectively. The association was confirmed in both left-sided colon cancer and rectal cancer, but was stronger for rectal cancer (P = .016). Alcoholism significantly enhanced the association by 7% (P = .027). Furthermore, prognostic advantage of metastatic LSCRC diminished among ever-smokers, with contrary survival impacts of smoking on either side of CRC.ConclusionsHistory of smoking was associated with LSCRC in a positive dose–response relationship, and presented opposite prognostic impacts on right- and left-sided tumors. Smoking potentially plays an instrumental role in the mechanism for sidedness heterogeneity in CRC.

Highlights

  • Colorectal cancer (CRC) is the third most common cancer and its mortality ranks fourth worldwide [1, 2]

  • We evaluated the relationship between cigarette smoking and colorectal cancer (CRC) sidedness based on a multi-center big-data intelligence platform with the aim of exploring potential tendencies for sidedness related to cigarette smoking, and assessed its potential prognostic influence regarding tumor sidedness

  • We further explored the prognostic effects of smoking and tumor sidedness on metastatic CRC (mCRC)

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Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer and its mortality ranks fourth worldwide [1, 2]. Previous studies have demonstrated a significant association of cigarette smoking with CRC incidence and mortality [5, 6]. Yang et al J Transl Med (2021) 19:150 have evaluated the association in subgroups of different primary tumor locations, and some proved it more solid for rectal cancer (RC) rather than colon cancer. This finding implied a differential susceptibility of carcinogenesis by cigarettes between subsites of colorectum. The present study aims to evaluate the sidedness tendency of cigarette smoking and to explore its impact on prognosis

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