Department of Epidemiology and Biostatistics, Guiling Medical University School of Public Health, Guilin, China.
PLoS One. 2012;7(7):e41853. doi: 10.1371/journal.pone.0041853. Epub 2012 Jul 27.
Excision repair cross-complementation group 4 gene (ERCC4/XPF) plays an important role in nucleotide excision repair and participates in removal of DNA interstrand cross-links and DNA double-strand breaks. Single nucleotide polymorphisms (SNPs) in ERCC4 may impact repair capacity and affect cancer susceptibility.
METHODOLOGY/PRINCIPAL FINDINGS: In this case-control study, we evaluated associations of four selected potentially functional SNPs in ERCC4 with risk of squamous cell carcinoma of the head and neck (SCCHN) in 1,040 non-Hispanic white patients with SCCHN and 1,046 cancer-free matched controls. We found that the variant GG genotype of rs2276466 was significantly associated with a decreased risk of SCCHN (OR = 0.69, 95% CI 0.50-0.96), and that the variant TT genotype of rs3136038 showed a borderline significant decreased risk with SCCHN (OR = 0.76, 95% CI: 0.58-1.01) in the recessive model. Such protective effects were more evident in oropharyngeal cancer (OR = 0.61, 95% CI: 0.40-0.92 for rs2276466; OR = 0.69, 95% CI: 0.48-0.98 for rs3136038). No significant associations were found for the other two SNPs (rs1800067 and rs1799798). In addition, individuals with the rs2276466 GG or with the rs3136038 TT genotypes had higher levels of ERCC4 mRNA expression than those with the corresponding wild-type genotypes in 90 Epstein-Barr virus-transformed lymphoblastoid cell lines derived from Caucasians.
These results suggest that these two SNPs (rs2276466 and rs3136038) in ERCC4 may be functional and contribute to SCCHN susceptibility. However, our findings need to be replicated in further large epidemiological and functional studies.
切除修复交叉互补基因 4 （ERCC4/XPF）在核苷酸切除修复中发挥重要作用，并参与 DNA 链间交联和 DNA 双链断裂的清除。ERCC4 中的单核苷酸多态性（SNP）可能影响修复能力并影响癌症易感性。
方法/主要发现：在这项病例对照研究中，我们评估了 ERCC4 中四个选定的潜在功能 SNP 与 1040 名非西班牙裔白人头颈部鳞状细胞癌（SCCHN）患者和 1046 名无癌症匹配对照者的 SCCHN 风险之间的关联。我们发现，rs2276466 的变异 GG 基因型与 SCCHN 风险降低显著相关（OR=0.69，95%CI 0.50-0.96），rs3136038 的变异 TT 基因型在隐性模型中与 SCCHN 风险呈临界性降低相关（OR=0.76，95%CI：0.58-1.01）。这种保护作用在口咽癌中更为明显（OR=0.61，95%CI：0.40-0.92 用于 rs2276466；OR=0.69，95%CI：0.48-0.98 用于 rs3136038）。对于其他两个 SNP（rs1800067 和 rs1799798），未发现显著相关性。此外，在 90 个源自白种人的 Epstein-Barr 病毒转化的淋巴母细胞系中，与相应野生型基因型相比，携带 rs2276466 GG 或 rs3136038 TT 基因型的个体 ERCC4 mRNA 表达水平更高。
这些结果表明，ERCC4 中的这两个 SNP（rs2276466 和 rs3136038）可能具有功能，并有助于 SCCHN 的易感性。然而，我们的研究结果需要在进一步的大型流行病学和功能研究中得到验证。
