Volatile Organic Compounds Emitted From Faeces as a Biomarker for Colorectal Cancer

Ashley Bond; Rosemary Greenwood; Stephen Lewis; Bernard Corfe; Sanchoy Sarkar; Paul O'Toole; Paul Rooney; Michael Burkitt; Georgina Hold; Chris Probert

Disclosures

Aliment Pharmacol Ther. 2019;49(8):1005-1012. 

In This Article

Abstract and Introduction

Abstract

Background: Colorectal cancer remains a leading cause of mortality and morbidity. The UK Bowel Cancer Screening Programme (BCSP) has demonstrated that detection of colorectal cancer at an earlier stage and identification of advanced pre-malignant adenomas reduces mortality and morbidity.

Aim: To assess the utility of volatile organic compounds as a biomarker for colorectal neoplasia.

Methods: Faeces were collected from symptomatic patients and people participating in the UK BCSP, prior to colonoscopy. Headspace extraction followed by gas chromatography mass spectrometry was performed on faeces to identify volatile organic compounds. Logistic regression modelling and 10-fold cross-validation were used to test potential biomarkers.

Results: One hundred and thirty-seven participants were included (mean age 64 years [range 22–85], 54% were male): 60 had no neoplasia, 56 had adenomatous polyp(s) and 21 had adenocarcinoma. Propan-2-ol was significantly more abundant in the cancer samples (P < 0.0001, q = 0.004) with an area under ROC (AUROC) curve of 0.76. When combined with 3-methylbutanoic acid the AUROC curve was 0.82, sensitivity 87.9% (95% CI 0.87-0.99) and specificity 84.6% (95% CI 0.65-1.0). Logistic regression analysis using the presence/absence of specific volatile organic compounds, identified a three volatile organic compound panel (propan-2-ol, hexan-2-one and ethyl 3-methyl-butanoate) to have an AUROC of 0.73, with a person six times more likely to have cancer if all three volatile organic compounds were present (P < 0.0001).

Conclusions: Volatile organic compound analysis may have a superior diagnostic ability for the identification of colorectal adenocarcinoma, when compared to other faecal biomarkers, including those currently employed in UK.

Clinical trial details: National Research Ethics Service Committee South West - Central Bristol (REC reference 14/SW/1162) with R&D approval from University of Liverpool and Broadgreen University Hospital Trust (UoL 001098).

Introduction

Colorectal cancer is a leading cause of mortality and morbidity worldwide, with an estimated European incidence of 43.5 per 100 000 in 2012 and mortality of 19.5 per 100 000.[1] The lifetime risk, for UK residents, is 1 in 15 for men or 1 in 19 for women.[2] Across Europe, colorectal cancer is the second most common cause of cancer-related mortality.[1] Colorectal cancer carries a significant financial burden for the National Health Service, with a mean annual cost of £12 000 and £8800 for each patient diagnosed with rectal and nonrectal colon cancer respectively.[3] Data from the UK Bowel Cancer Screening Programme have clearly demonstrated that detection of colorectal cancer at an earlier stage and identification of advanced pre-malignant adenomas can reduce future cancer-associated mortality and morbidity.[4,5]

The UK Bowel Cancer Screening Programme uses a faeces-based screening tool to select patients to take forward to colonoscopy, in line with European guidance.[6] Currently, in England, the guaiac-based faecal occult blood testing (gFOBt) is employed. This test relies on bleeding from neoplastic lesions and can be used to identify people with >10 mL rectal blood loss daily. gFOBt is however, prone to false positive results after ingestion of certain foods.[7] The low sensitivity of gFOBt has led to criticism of its use for population-based screening.[8] The gFOBt is likely to be replaced by faecal immunochemical testing (FIT). FIT detects twice as many advanced cancers as guaiac testing[9] and can provide both qualitative and quantitative results. A recent observational study, from Italy, demonstrated a reduction in colorectal cancer-related mortality in regions where screening with FIT was adopted compared with regions where screening had not yet been implemented.[10,11] Burch et al[4] reported a meta-analysis of 59 studies of FOBT: sensitivities for the detection of all neoplasms ranged from 6.2% to 83.3% for gFOBTs and 5.4% to 62.6% for FITs, depending on the preferred specificity.[12] A review by NICE concluded that FIT has a specificity ranging from 43% to 86%.[13] However, FIT has limitations: the Dutch colorectal cancer screening programme reported 77% sensitivity with FIT based on 18 716 samples (specificity was not reported) and 23% of the patients developed interval cancers.[14]

Several studies have reported volatile organic compounds emitted from different substrates as biomarkers for colorectal cancer. One such study used selected ion flow tube mass spectrometry (SIFT-MS) to detect volatile organic compounds in faeces.[15] Another analysed urine, from patients with colorectal cancer, employing Field Asymmetric Ion Mobility Spectrometer (FAIMS).[16] The third used breath analysed by thermal-desorber gas chromatography–mass spectrometry (GCMS) in an attempt to diagnose colorectal cancer.[17,18] These were mainly proof of concept or feasibility studies that reported output patterns rather than identifying the individual compounds. Therefore, understanding the biological plausibility for patterns of volatile organic compounds can be difficult to interpret.

We undertook a prospective study of the volatile organic compounds emitted from faecal samples obtained from patients at risk of colorectal cancer.

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