Genetic variation in the prostate stem cell antigen gene and upper gastrointestinal cancer in white individuals.
OBJECTIVE
An association between gastric cancer and the rs2294008 (C>T) polymorphism in the prostate stem cell antigen (PSCA) gene has been reported for several Asian populations. We set out to determine whether such an association exists in white individuals.


METHODS
We genotyped 166 relatives of gastric cancer patients, including 43 Helicobacter pylori-infected subjects with hypochlorhydria and gastric atrophy, 65 infected subjects without these abnormalities, 58 H pylori-negative relatives, and 100 population controls. Additionally, a population-based study of chronic atrophic gastritis provided 533 cases and 1054 controls. We then genotyped 2 population-based, case-control studies of upper gastrointestinal cancer: the first included 312 gastric cancer cases and 383 controls; the second included 309 gastric cancer cases, 159 esophageal cancer cases, and 211 controls. Odds ratios were computed from logistic models and adjusted for confounding variables.


RESULTS
Carriage of the risk allele (T) of rs2294008 in PSCA was associated with chronic atrophic gastritis (adjusted odds ratio [OR], 1.5; 95% confidence interval [CI]: 1.1-1.9) and noncardia gastric cancer (OR, 1.9; 95% CI: 1.3-2.8). The association was strongest for the diffuse histologic type (OR, 3.2; 95% CI: 1.2-10.7). An inverse association was observed between carriage of the risk allele and gastric cardia cancer (OR, 0.5; 95% CI: 0.3-0.9), esophageal adenocarcinoma (OR, 0.5; 95% CI: 0.3-0.9), and esophageal squamous cell carcinoma (OR, 0.4; 95% CI: 0.2-0.9).


CONCLUSIONS
The rs2294008 polymorphism in PSCA increases the risk of noncardia gastric cancer and its precursors in white individuals but protects against proximal cancers.
Gastrointestinal Research Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland.
Paul
P
Lochhead
Bernd
B
Frank
Georgina L
GL
Hold
Charles S
CS
Rabkin
Michael T H
MT
Ng
Thomas L
TL
Vaughan
Harvey A
HA
Risch
Marilie D
MD
Gammon
Jolanta
J
Lissowska
Melanie N
MN
Weck
Elke
E
Raum
Heiko
H
Müller
Thomas
T
Illig
Norman
N
Klopp
Alan
A
Dawson
Kenneth E
KE
McColl
Hermann
H
Brenner
Wong-Ho
WH
Chow
Emad M
EM
El-Omar
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D005757:Gastritis, Atrophic / Q000453:epidemiology / Q000235:genetics; D005770:Gastrointestinal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000453:epidemiology / Q000235:genetics; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D044465:White People / Q000235:genetics
D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human