Polymorphisms of XRCC1 and risk of esophageal and gastric cardia cancer.
BACKGROUND
Linxian, a rural county in North Central China, has among the highest rates of esophageal squamous cell carcinoma and gastric cardia adenocarcinoma in the world. In a nested case-cohort study that originated from two cancer prevention trials in Linxian, we examined the relationship between these cancers and two polymorphisms in the DNA repair gene XRCC1.


METHODS
We conducted a case-cohort study among individuals in the cohort who were alive and cancer free in 1991, and had blood samples for DNA extraction. Real time Taqman analyses were conducted to genotype incident cancer cases (n = 221, 131 esophageal and 90 gastric cardia cancer cases) that developed through May 1996, and on an age- and sex-matched reference cohort (n = 454). We used Cox proportional hazard models to estimate relative risks (RR) and 95% confidence intervals (95% CI).


RESULTS
We observed no association between the variant genotype in XRCC1 Arg194Trp (codon 194 arganine to tryptophan substitution) and esophageal or gastric cardia cancer. However, carrying at least one copy of the variant allele in XRCC1 Arg399Gln (codon 399 arganine to glutamine substitution) was associated with reduced risk of gastric cardia cancer (RR: 0.60, 95% CI: 0.37-0.97) and the combined category esophageal/gastric cancer (RR: 0.67, 95% CI: 0.48-0.95). In combined polymorphisms analyses, we observed a significant reduction in risk of combined esophageal/gastric cancer among individuals that had both the XRCC1 Arg194Trp and Arg399Gln variant genotyopes (RR: 0.47, 95% CI: 0.26-0.84).


CONCLUSIONS
Our results suggest that the XRCC1 Arg399Gln variant genotype is associated with reduced risk of upper GI cancer and that individuals with both XRCC1 variant genotypes are also at significantly reduced risk of upper GI cancer in this high-risk Chinese population.
Ratnasinghe
Luke D
LD
Center for Structural Genomics, NCTR, Food and Drug Administration, National Center for Toxicological Research/FDA, 3900 NCTR Drive, Jefferson, Arkansas, AR 72079-9502, USA. lratnasinghe@nctr.fda.gov
Abnet
Christian
C
Qiao
You-Lin
YL
Modali
Rama
R
Stolzenberg-Solomon
Rachael
R
Dong
Zhi-Wei
ZW
Dawsey
Sanford M
SM
Mark
Steven D
SD
Taylor
Philip R
PR
D044466:Asian People / Q000235:genetics; D002299:Cardia / Q000473:pathology*; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics; D011110:Polymorphism, Genetic; D012306:Risk; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human