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

Authors: MIRANTI, EUGENIA - National Institutes Of Health (NIH); FREEDMAN, NEAL - National Institutes Of Health (NIH); WEINSTEIN, STEPHANIE - National Institutes Of Health (NIH); ABNET, CHRISTIAN - National Institutes Of Health (NIH); SELHUB, JACOB - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MURPHY, GWEN - National Institutes Of Health (NIH); DIAW, LENA - National Institutes Of Health (NIH); MANNISTO, SATU - National Institute For Health And Welfare (HELSINKI); TAYLOR, PHILIP - National Institutes Of Health (NIH); ALBANES, DEMETRIUS - National Institutes Of Health (NIH); STOLZENBERG-SOLOMON, RACHAEL - National Institutes Of Health (NIH)

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/30/2016
Publication Date: 8/17/2016
Citation: Miranti, E.H., Freedman, N.D., Weinstein, S.J., Abnet, C.C., Selhub, J., Murphy, G., Diaw, L., Mannisto, S., Taylor, P.R., Albanes, D., Stolzenberg-Solomon, R.Z. 2016. Prospective study of serum cysteine and cysteinylglycine and cancer of the head and neck, esophagus, and stomach in a cohort of male smokers. American Journal of Clinical Nutrition. https://doi.org/10.3945/ajcn.115.125799.

Interpretive Summary: Cysteine is a non-essential amino acid found in proteins that we digest and is also formed in the body. Cysteinylglycine is a structure of two amino acids, cysteine and glycine, which is formed when glutathione is degraded. Glutathione is formed in the body and is a major protector against oxidative stress. In this study we looked at the relationships between blood levels of cysteine and cysteinylglycine and risk of development of certain cancers in male smokers. The data obtained suggest that both low and high cysteine concentrations in plasma are associated with developing stomach cancer. High levels of cysteinylglycine in serum may be inversely related to the development of cancer in the upper part of the stomach.

Technical 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.