Dong Xiu-Juan, Wang Na, Guo Wei, Zhou Rong-Miao, Zhang Xiao-Juan, Li Yan
Lab of Molecular Biology, Hebei Provincial Cancer Institute, Shijiazhuang, Hebei, PR China.
Ai Zheng. 2007 Mar;26(3):280-4.
BACKGROUND & 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.
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.
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).
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.
XRCC5是一种DNA双链断裂修复基因。其异常表达及功能障碍与肿瘤的发生发展相关。本研究旨在探讨中国河北省磁县和涉县高发地区人群中XRCC5基因多态性与食管鳞状细胞癌（ESCC）和贲门腺癌（GCA）遗传易感性的相关性。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析法检测329例ESCC患者、255例GCA患者及631例健康对照者XRCC5单核苷酸多态性（SNP）C74468A和G74582A的基因型。
ESCC和GCA患者中XRCC5 C74468A和G74582A的总体基因型和等位基因型分布与健康对照者无显著差异（P>0.05）。按吸烟状况和上消化道癌（UGIC）家族史分层时，C74468A的A等位基因（A/C+A/A基因型）在UGIC家族史阳性组中显著降低了发生ESCC和GCA的风险[年龄、性别和吸烟状况校正比值比（OR）分别为0.58和0.61，95%置信区间（CI）分别为0.38 - 0.90和0.38 - 0.97]；G74582A的G等位基因（A/G+G/G基因型）在UGIC家族史阳性组中显著降低了发生GCA的风险（年龄、性别和吸烟状况校正OR = 0.63，95%CI = 0.40 - 0.98）。对2个XRCC5 SNP进行联合分析显示，ESCC和GCA患者的单倍型分布与健康对照者也无显著差异（P>0.05）。
在河北省高发地区UGIC家族史阳性人群中，携带XRCC5 C74468A的A等位基因个体发生ESCC和GCA的风险可能较低，然而，携带XRCC5 G74582A的G等位基因个体可能仅发生GCA的风险较低。
