Body Mass Index, sex, non-steroidal anti-inflammatory drug medications, smoking and alcohol are differentially associated with World Health Organisation criteria and colorectal cancer risk in people with Serrated Polyposis Syndrome: an Australian case-control study

Abstract

Objective: The unknown aetiology of Serrated Polyposis Syndrome (SPS) impedes risk prediction and prevention. We investigated risk factors for SPS, overall and stratified by World Health Organization (WHO)²⁰¹⁰ clinical criteria and by colorectal cancer (CRC).

Method: A retrospective case-control study involving a cross-sectional analysis from 350 unrelated individuals with SPS from the Genetics of Colonic Polyposis Study and 714 controls from the Australasian Colorectal Cancer Family Registry. Univariate and multivariate logistic regression modelling was used to determine the association between risk factors and SPS and risk factors associated with CRC in SPS.

Results: Female biological sex (odds ratio (OR) = 4.54; 95%Confidence interval (CI) = 2.77-7.45), increasing body mass index (BMI) at age 20 years (OR = 1.09; 95%CI = 1.04-1.13), hormone replacement therapy (OR = 0.44; 95%CI = 0.20.98), and increasing weekly folate intake (OR = 0.82; 95%CI = 0.75-0.90) were associated with SPS by multivariate analysis. Increasing weekly calcium intake (OR = 0.79; 95%CI = 0.64-0.97) and smoking > 10 cigarettes daily (OR = 0.45; 95%CI = 0.23-0.86) were associated with WHO criterion I only. The consumption of 1-100 g of alcohol per week (OR = 0.39; 95%CI = 0.18-0.83) was associated with WHO criterion III only. Smoking 1-5 cigarettes daily (OR = 2.35; 95%CI = 1.09-5.05), weekly non-steroidal anti-inflammatory drug (NSAIDs) intake (OR = 0.88; 95%CI = 0.78-0.99), and increased height (OR = 1.09; 95% = 1.05-1.13), were associated with SPS fulfilling both WHO criteria I and III. Moreover, weekly NSAIDs intake (OR = 0.81; 95%CI = 0.67-0.98) was associated with a reduced likelihood of CRC in SPS.

Conclusion: We identified novel risk and potential protective factors associated with SPS, some specific for certain WHO²⁰¹⁰ criteria. Weekly use of NSAIDs may reduce the risk of CRC in people with SPS.

Keywords: Alcohol; BMI; Calcium; Case-control; Cigarettes; Colorectal cancer; Folate; Height; Hormone replacement therapy; Logistic regression; Medication; Modifiable factors; Multivariate analysis; Multivitamin; NSAIDs; Pregnancy; Serrated polyposis syndrome; Sex; World Health Organization.

Fig. 1

Forest plots summarizing odds ratio (OR) and 95% confidence intervals (CI) for each characteristic and risk factor. A OR and 95% CI for characteristics and risk factors for all SPS (black dots) and stratified by SPS WHO criteria (WHO²⁰¹⁰ criteria I = blue square; WHO²⁰¹⁰ criteria III = green triangle; Both WHO²⁰¹⁰ criteria I and III = red diamond) vs. controls B OR and 95% CI for characteristics and risk factors for all SPS (black dots) and stratified by SPS CRC status (developed CRC = blue square; did not develop CRC = green triangle) vs. controls. C OR and 95% CI for characteristics and risk factors for all SPS (black dots) and stratified by SPS WHO criteria (WHO²⁰¹⁰ criteria I = blue square; WHO²⁰¹⁰ criteria III = green triangle; Both WHO²⁰¹⁰ criteria I and III = red diamond) vs. controls for females only. D OR and 95% CI for characteristics and risk factors for all SPS (black dots) and stratified by SPS CRC status (developed CRC = blue square; did not develop CRC = green triangle) vs. controls for females only. Variables were excluded from the figure if they were not included in the multivariate model (p-value of > 0.15 and > 20% missing data in the univariate analysis)