Blood biomarkers for early diagnosis of oesophageal cancer: a systematic review

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Oesophageal cancer prognosis remains poor owing to the inability to detect the disease at an early stage. Nontissue (serum, urinary or salivary) biomarkers potentially offer less invasive methods to aid early detection of oesophageal cancer. We aimed to systematically review studies assessing the relationship between nontissue biomarkers and subsequent development of oesophageal cancer.


Using terms for biomarkers and oesophageal cancer, Medline, EMBASE and Web of Science were systematically searched for longitudinal studies, published until April 2016, which assessed the association between nontissue biomarkers and subsequent oesophageal cancer risk. Random effects meta-analyses were used to calculate pooled relative risk (RR) and 95% confidence intervals (CIs), where possible.


A total of 39 studies were included. Lower serum pepsinogen I concentrations were associated with an increased risk of oesophageal squamous cell carcinoma (n=3 studies, pooled RR=2.20, 95% CI: 1.31–3.70). However, the association for the pepsinogen I : II ratio was not statistically significant (n=3 studies, pooled RR=2.22, 95% CI: 0.77–6.40), with a large degree of heterogeneity observed (I2=68.0%). Higher serum glucose concentrations were associated with a modestly increased risk of total oesophageal cancer (n=3 studies, pooled RR=1.27, 95% CI: 1.02–1.57). No association was observed for total cholesterol and total oesophageal cancer risk (n=3 studies, pooled RR=0.95, 95% CI: 0.58–1.54). Very few studies have assessed other biomarkers for meta-analyses.


Serum pepsinogen I concentrations could aid early detection of oesophageal squamous cell carcinoma. More prospective studies are needed to determine the use of other nontissue biomarkers in the early detection of oesophageal cancer.

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