Prospective study of serum cysteine and cysteinylglycine and cancer of the head and neck, esophagus, and stomach in a cohort of male smokers

Abstract

Background: The nonessential amino acid cysteine is known to be involved in many antioxidant and anticarcinogenic pathways. Cysteinylglycine is a pro-oxidant metabolite of glutathione and a precursor of cysteine.

Objective: To examine the relation between serum cysteine and cysteinylglycine and risk of gastric adenocarcinomas, esophageal squamous cell carcinomas, and head and neck squamous cell carcinomas, we conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study of male Finnish smokers aged 50-69 y at baseline.

Design: In total, 170 gastric adenocarcinomas, 68 esophageal squamous cell carcinomas, and 270 head and neck squamous cell carcinomas (identified from the Finnish Cancer Registry) were matched one-to-one with cancer-free control subjects on age and the date of serum collection. We calculated ORs and 95% CIs with the use of a multivariate-adjusted conditional logistic regression.

Results: Cysteine had a U-shaped association with gastric adenocarcinomas; a model that included a linear and a squared term had a significant global P-test (P = 0.036). Serum cysteinylglycine was inversely associated with adenocarcinomas of the gastric cardia (OR for above the median compared with below the median: 0.07; 95% CI: 0.01, 0.70; n = 38 cases) but not for other sites. Both cysteine and cysteinylglycine were not associated with esophageal squamous cell carcinoma or head and neck squamous cell carcinoma.

Conclusions: We observed associations between serum cysteine and cysteinylglycine with upper gastrointestinal cancer risk. Future studies are needed to replicate these findings. This trial was registered at clininicaltrials.gov as NCT00342992.

Keywords: cysteine; esophageal neoplasms; head and neck neoplasms; stomach neoplasms; upper gastrointestinal tract cancers.

© 2016 American Society for Nutrition.

Figures

FIGURE 1

OR (95% CIs) for the association between serum cysteine and cancer risk relative to the median of the first quartile. We calculated estimates from models with both linear and quadratic terms for serum cysteine with adjustment for age, alcohol intake, BMI, energy intake, cigarettes smoked per day, years of cigarette smoking, education, fruit intake, vegetable intake, gastric adenocarcinomas, and Helicobacter pylori seropositivity. For gastric adenocarcinomas, we observed evidence of a nonlinear association with a P value for the quadratic term of 0.037 and the overall 2-df test for an association of 0.036. For esophageal squamous tumors, we showed no evidence of a deviation from linearity (for the quadratic term: P value= 0.46; for the 2-df test: P = 0.19). For head and neck squamous tumors, we showed no evidence of a deviation from linearity (for the quadratic term: P = 0.19; for the 2-df test: P = 0.34). Q, quartile.