DNA repair genes XPC, XPD, XRCC1, and XRCC3 are associated with risk and survival of squamous cell carcinoma of the head and neck
DNA repair genes XPC, XPD, XRCC1, and XRCC3 are associated with risk and survival of squamous cell carcinoma of the head and neck
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DOI：
10.1016/j.dnarep.2015.05.003
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发表时间：
2015-07-01
期刊：
影响因子：
3.8
通讯作者：
Thunell, Lena K.
中科院分区：
文献类型：
--
作者：
Farnebo, Lovisa;Stjernstrom, Annika;Thunell, Lena K.
头颈部鳞状细胞癌（HNSCC）是一组异质性肿瘤，具有高的早期复发率、第二原发肿瘤率和死亡率。尽管在过去的几十年里诊断和治疗取得了进展，但总体5年生存率仍保持在50%左右。由于头颈部持续暴露于潜在的DNA损伤性外源性和内源性因素，因此可以合理地预期DNA修复基因在HNSCC的发生、进展和结局中发挥作用。本研究的目的是调查SNPs XPC A499 V、XPD K751 Q、XRCC 1 R399 Q和XRCC 3 T241 M作为高加索患者生存的潜在危险因素和指标。169例患者以及344名健康对照者被纳入，并采用PCR-RFLP进行基因分型。我们发现XPC A499 V与HNSCC，尤其是喉癌的风险增加有关。在女性中，XPD K751 Q与口腔SCC风险增加相关。此外，XPD纯合子突变个体的生存时间最短，但在全剂量放疗后生存时间增加。XRCC 3 T241 M的野生型个体表现出较早的发病年龄。HPV阳性从不吸烟者p53突变频率较低。在HNSCC患者中，HPV阳性与XRCC 1 R399 Q纯合突变基因型显著相关。此外，推定风险等位基因的组合似乎具有协同作用，增加了HNSCC的风险。总之，我们的研究结果表明，DNA修复基因XPC，XPD，XRCC 1和XRCC 3的SNP可能会影响HNSCC的风险和生存。(C)2015 Elsevier B. V.版权所有。
Head and neck squamous cell carcinomas (HNSCC) are a heterogenous group of tumors with a high rate of early recurrences, second primary tumors, and mortality. Despite advances in diagnosis and treatment over the past decades, the overall 5-year survival rate remains around 50%. Since the head-and neck-region is continuously exposed to potentially DNA-damaging exogenous and endogenous factors, it is reasonable to expect that the DNA repair genes play a part in the development, progression, and outcome of HNSCC. The aim of this study was to investigate the SNPs XPC A499V, XPD K751Q XRCC1 R399Q and XRCC3 T241M as potential risk factors and indicators of survival among Caucasian patients. One-hundred-sixty-nine patients as well as 344 healthy controls were included and genotyped with PCR-RFLP. We showed that XPC A499V was associated with increased risk of HNSCC, especially laryngeal carcinoma. Among women, XPD K751Q was associated with increased risk of oral SCC. Furthermore, XPD homozygous mutant individuals had the shortest survival time, a survival time that increased however after full dose radiotherapy. Wild-type individuals of XRCC3 T241M demonstrated an earlier age of onset. HPV-positive never smokers had lower frequencies of p53 mutation. Among HNSCC patients, HPV-positivity was significantly associated with XRCC1 R399Q homozygous mutant genotype. Moreover, combinations of putative risk alleles seemed to act synergistically, increasing the risk of HNSCC. In conclusion, our results suggest that SNPs of the DNA repair genes XPC, XPD, XRCC1, and XRCC3 may affect risk and survival of HNSCC. (C) 2015 Elsevier B.V. All rights reserved.