Serum pepsinogens and Helicobacter pylori in relation to the risk of esophageal squamous cell carcinoma in the alpha-tocopherol, beta-carotene cancer prevention study.
BACKGROUND
Helicobacter pylori can induce gastric atrophy in humans, which in turn increases gastric cancer risk. Whether H. pylori and gastric atrophy also affect the risk of esophageal squamous cell carcinoma (ESCC), however, remains unresolved.


METHODS
We performed a nested case-control study within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to assess these relationships. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study is composed of 29,133 Finnish male smokers, ages 50 to 69 years, who were recruited during 1985-1988. Using baseline sera, we assessed H. pylori status (via immunoglobulin G antibodies against whole-cell and CagA antigens) and gastric atrophy status [via the biomarkers pepsinogen I (PGI) and pepsinogen II (PGII)] in 79 ESCC cases and 94 controls. Logistic regression with adjustment for age, date of blood draw, education, cigarette smoking, alcohol, body mass index, and fruit and vegetable intake was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI).


RESULTS
Gastric atrophy (PGI/PGII <4) was associated with ESCC (OR, 4.58; 95% CI, 2.00-10.48). There was no evidence for an association between H. pylori and ESCC (OR, 0.94; 95% CI, 0.40-2.24).


CONCLUSIONS
These results could be explained by misclassification of H. pylori status due to serologic amnesia, ESCC risk being dependent on the functional consequences or interactions of H. pylori rather than the infection per se, gastric atrophy having a different histogenesis in ESCC without being primarily dependent on H. pylori acquisition, or a lack of statistical power to detect an effect.


CONCLUSIONS
Validation of these results may warrant mechanistic studies to determine the route of association between gastric atrophy and ESCC.
Cook
Michael B
MB
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health/DHHS, 6120 Executive Boulevard, Bethesda, MD 20852-7234, USA. michael.cook@nih.gov
Dawsey
Sanford M
SM
Diaw
Lena
L
Blaser
Martin J
MJ
Perez-Perez
Guillermo I
GI
Abnet
Christian C
CC
Taylor
Philip R
PR
Albanes
Demetrius
D
Virtamo
Jarmo
J
Kamangar
Farin
F
D000368:Aged; D001284:Atrophy; D015415:Biomarkers / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000453:epidemiology* / Q000382:microbiology; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000382:microbiology; D005387:Finland / Q000453:epidemiology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010435:Pepsinogens / Q000097:blood*; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D012907:Smoking; D013270:Stomach / Q000473:pathology*; D024502:alpha-Tocopherol; D019207:beta Carotene
D015415:Biomarkers; D010435:Pepsinogens; D019207:beta Carotene; D024502:alpha-Tocopherol