RANTES-403 polymorphism is associated with reduced risk of gastric cancer in women.
BACKGROUND
Men are more susceptible to gastric cancer (GC) than women. However, the genetic factors associated with the sex difference are not well understood. Chemokines have been shown to modulate tumor behavior, and the sex-specific effect of the chemokine polymorphisms on the host susceptibility to several diseases has been reported. We aimed to determine the role of chemokine polymorphisms on host susceptibility to GC, with special interest on their sex-specific effect.


METHODS
A hospital-based case-control study, including 177 patients with GC and 217 age-matched unaffected healthy controls, was performed in three major tertiary care hospitals. Genotyping for regulated upon activation, normal T-cell expressed and secreted (RANTES) -403 A/G and -28 C/G, CC chemokine receptor 5 (CCR5) deletion, and CCR2-V64I was performed using peripheral blood DNA.


RESULTS
The RANTES -403 GA and AA genotypes were independently associated with a 2.3-fold reduced risk of developing GC (OR=0.44, 95% CI 0.22-0.90, P=0.025) compared with GG genotype in women, but not in men. The RANTES -28C/G and CCR2-V64I polymorphisms were not associated with different risk of developing GC. The tumor stage, histological features, and survival rate were not different when stratified by RANTES -403 and -28 and CCR2-V64I genotypes.


CONCLUSIONS
Our data indicate that women who inherit A allele at RANTES -403 may be at reduced risk of GC.
Liou
Jyh-Ming
JM
Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, No. 7, Chung-Shan S. Road, Taipei, Taiwan.
Lin
Jaw-Town
JT
Huang
Shih-Pei
SP
Wu
Chun-Ying
CY
Wang
Hsiu-Po
HP
Lee
Yi-Chia
YC
Chiu
Han-Mo
HM
Shun
Chia-Tung
CT
Lin
Ming-Tsan
MT
Wu
Ming-Shiang
MS
D000368:Aged; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011110:Polymorphism, Genetic; D054390:Receptors, CCR2 / Q000235:genetics; D018570:Risk Assessment; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D016019:Survival Analysis
C515334:CCR2 protein, human; D018946:Chemokine CCL5; D054390:Receptors, CCR2