WWOX基因的遺傳變異分佈與子宮頸癌的關係

據我們所知，目前並沒有研究調查雙色胺酸功能區氧化還原酶 (ww domain-containing oxidoreductase ; WWOX) 基因的遺傳變異分佈與侵襲性癌症、臨床病理特徵和子宮頸癌患者對於台灣婦女存活率的關聯，因此我們進行台灣女性WWOX基因多型性與子宮頸癌臨床病理特徵和存活率之間相關性的探討。本研究納入131名患有子宮頸侵襲癌患者與93名癌前病變患者，以及316名健康對照婦女。利用即時聚合酶鏈式反應來測定WWOX基因中rs73569323 [exon 8, mRNA position 1683 C>T; 3’ untranslated region (3’UTR)]、rs383362 (exon 8, 1738 G>T; 3’UTR)、rs11545028 (exon 1, 362 C>T; 5’UTR)、rs3764340 (exon 7, 1210 C>G) and rs12918952 (exon 5, 901 G>A)的變異。研究結果發現在5個WWOX遺傳變異中，只有WWOX rs3764340在子宮頸侵襲癌患者與正常控制組有相關性。子宮頸癌患者帶有WWOX rs12918952 GA/AA表現型與子宮旁侵犯和骨盆腔淋巴結轉移有相關。另外，在單一變量分析發現WWOX rs73569323和rs11545028與病人的存活率有相關性，然而多變量分析顯示，在5個WWOX遺傳變異中，只有rs11545028 CT/TT可以預測更好地總體存活率。總之，台灣女性WWOX rs3764340 帶有CG/GG基因表現型者，較容易罹患子宮頸侵襲癌。rs12918952 帶有GA/AA基因型者，有較高的危險性發展成子宮旁侵犯與盆腔淋巴結轉移。在5個WWOX遺傳變異中，只有rs11545028是與病人存活率有相關，其中帶有CT/TT基因型者，可以預測台灣女性更好的整體存活期。

To our knowledge, no study investigates the association of genetic variant distributions of WW domain-containing oxidoreductase (WWOX) gene with development of invasive cancer, clinicopathologic variables and patient survival in uterine cervical cancer for Taiwanese women. We therefore conducted this study to explore the clinical involvements of WWOX single nucleotide polymorphisms (SNPs) in cervical cancer. One hundred and thirty-one patients with cervical invasive cancer and 93 patients with precancerous lesions as well as 316 control women were consecutively enrolled. The genotypic frequencies of WWOX genetic variants rs73569323, rs383362, rs11545028, rs3764340 and rs12918952 were determined by real-time polymerase chain reaction. The results revealed that only WWOX SNP rs3764340 was associated between patients with cervical invasive cancer and normal controls among 5 WWOX genetic variants. Cervical cancer patients with genotypes GA/AA in WWOX SNP rs12918952 were associated with parametrium invasion and pelvic lymph node metastasis. Univariate analysis found that WWOX SNPs rs73569323 and rs11545028 were associated with patient survival, whereas multivariate analysis revealed CT/TT in rs11545028 was the only genetic variant, which could predict better overall survival, among 5 WWOX SNPs in Taiwan. In conclusion, Taiwanese women with CG/GG in WWOX SNP rs3764340 are susceptible to cervical invasive cancer. Cervical cancer patients with GA/AA in rs12918952 tend to have more risk to develop parametrium invasion and pelvic lymph node metastasis. Among 5 WWOX SNPs, rs11545028 is the only genetic variant associated with patient survival, in which CT/TT could predict better overall survival in Taiwanese women.