[Correlations of XRCC5 polymorphisms to genetic susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in a high incidence region].
OBJECTIVE
XRCC5 is a repair gene for DNA double-strand break. Its abnormal expression and dysfunction is correlated to tumorigenesis and development. This study was to investigate the correlations of XRCC5 polymorphisms to genetic susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of high incidence region, Cixian and Shexian counties of Hebei Province, China.


METHODS
The genotypes of XRCC5 single nucleotide polymorphisms (SNPs), C74468A and G74582A, in 329 ESCC patients, 255 GCA patients, and 631 healthy controls were detected by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) analysis.


RESULTS
The overall genotype and allelotype distributions of XRCC5 C74468A and G74582A in ESCC and GCA patients were not significantly different from those in healthy controls (P>0.05). When stratified by smoking status and family history of upper gastrointestinal cancer (UGIC), A allele (A/C+A/A genotype) of C74468A significantly reduced the risk of developing ESCC and GCA in positive UGIC family history group [age, sex, and smoking status adjusted odds ratios (ORs) were 0.58 and 0.61, 95% confidence intervals (CIs) were 0.38-0.90 and 0.38-0.97, respectively]û G allele (A/G+G/G genotype) of G74582A significantly reduced the risk of developing GCA in positive UGIC family history group (age, sex, and smoking status adjusted OR=0.63, 95% CI=0.40-0.98). Combined analysis of the 2 XRCC5 SNPs showed that the haplotype distribution in ESCC and GCA patients was also not significantly different from that in healthy controls (P> 0.05).


CONCLUSIONS
In the population with positive UGIC family history in the high incidence region of Hebei Province, individuals with A allele of XRCC5 C74468A might have low risk of developing ESCC and GCA, however, individuals with G allele of XRCC5 G74582A might only have low risk of developing GCA.
Dong
Xiu-Juan
XJ
Lab of Molecular Biology, Hebei Provincial Cancer Institute, Shijiazhuang, Hebei, PR China.
Wang
Na
N
Guo
Wei
W
Zhou
Rong-Miao
RM
Zhang
Xiao-Juan
XJ
Li
Yan
Y
D000230:Adenocarcinoma / Q000235:genetics*; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002299:Cardia / Q000473:pathology; D002681:China / Q000453:epidemiology; D016001:Confidence Intervals; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012907:Smoking; D013274:Stomach Neoplasms / Q000235:genetics*
D004265:DNA Helicases; C106893:XRCC5 protein, human; D000072200:Ku Autoantigen