Abstract
BACKGROUND: Cancers of the upper gastrointestinal tract remain a significant cause of morbidity and mortality. Cysteine, known to be involved in a myriad of immuno-modulatory, anti-oxidant, and anti-carcinogenic pathways, has not been investigated in the aetiology of oesophageal or gastric cancers. To examine the relationship between serum cysteine concentration and risk of these cancers we conducted a nested case-cohort study within the General Population Nutrition Intervention Trial in Linxian, China. METHODS: 498 oesophageal squamous cell carcinomas (OSCCs) and 255 gastric cardia adenocarcinomas (GCAs) were matched by age and sex to 947 individuals from the wider cohort. We calculated HRs and 95% CIs using the case-cohort estimator for the Cox proportional hazards models, stratified on age and sex, with adjustment for potential confounders. RESULTS: Higher concentrations of serum cysteine were significantly associated with a lower risk of both OSCC and GCA. For those in the highest quartile of serum cysteine, compared to those in the lowest, the multivariate HRs were 0.70 for OSCC (95% CI 0.51 to 0.98) and 0.59 for GCA (95% CI 0.38 to 0.91). These associations were dose dependent (p for trend=0.006 and 0.008, respectively). These inverse associations were not significantly modified by other risk factors, with the exception of age, where a stronger association was noted among persons in the older age strata. CONCLUSION: Higher serum concentrations of cysteine were associated with a significantly reduced risk of OSCC and GCA. Cysteine should be further investigated for its potential as a chemopreventive agent for upper gastrointestinal cancers.