Functional genetic variant in the Kozak sequence of WW domain-containing oxidoreductase (WWOX) gene is associated with oral cancer risk.
Functional genetic variant in the Kozak sequence of WW domain-containing oxidoreductase (WWOX) gene is associated with oral cancer risk.
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DOI：
10.18632/oncotarget.12082
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发表时间：
2016-10-25
期刊：
影响因子：
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通讯作者：
Lin CW
中科院分区：
文献类型：
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作者：
Cheng HL;Liu YF;Su CW;Su SC;Chen MK;Yang SF;Lin CW
在台湾，口腔癌是男性第四大癌症，与接触环境致癌物质有关。含WW结构域的氧化还原酶(WWOX)是一种肿瘤抑制基因，与多种癌症的发生发展有关。我们假设WWOX的基因变异会影响口腔癌的易感性。对761例男性口腔癌患者和1199例男性非肿瘤患者的WWOX基因的5个多态性进行了基因分型。我们观察到携带WWOX rs11545028等位基因的个体更容易患口腔癌。此外，与野生型基因相比，晚期口腔癌患者具有变异基因TT的WWOX rs11545028多态频率更高。另一项整合到计算机的分析证实，rs11545028影响WWOX的表达，这与肿瘤的表达显著相关，并随后与肿瘤的发展和侵袭性有关。综上所述，WWOX基因变异有助于口腔癌的发生，有关这些生物标记物的研究结果为风险评估提供了预测模型。
In Taiwan, oral cancer is the fourth leading cancer in males and is associated with exposure to environmental carcinogens. WW domain-containing oxidoreductase (WWOX), a tumor suppressor gene, is associated with the development of various cancers. We hypothesized that genetic variants of WWOX influence the susceptibility to oral cancer. Five polymorphisms of WWOX gene from 761 male patients with oral cancer and 1199 male cancer-free individuals were genotyped. We observed that individuals carrying the polymorphic allele of WWOX rs11545028 are more susceptible to oral cancer. Furthermore, patients with advanced-stage oral cancer were associated with a higher frequency of WWOX rs11545028 polymorphisms with the variant genotype TT than did patients with the wild-type gene. An additional integrated in silico analysis confirmed that rs11545028 affects WWOX expression, which significantly correlates with tumor expression and subsequently with tumor development and aggressiveness. In conclusion, genetic variants of WWOX contribute to the occurrence of oral cancer, and the findings regarding these biomarkers provided a prediction model for risk assessment.