XRCC1 T-77C基因多型性對手術後非小細胞肺癌預後之影響

研究目的：XRCC1是一種鹼基刪除DNA修補 (base excision repair) 基因。已知該基因有十七個基因多型性，其中位於促進子之T-77C基因多型性可調節基因的轉錄與人類肺癌症發生之相關性，在國外只有少數研究報告有提及。 XRCC1之T-77C基因型中具有TC或CC基因型者較TT者有較低轉錄活性，使其DNA修復蛋白複製量減少，故修復傷害的能力降低，因而增加罹患肺癌發生之風險。在此本研究嘗試證明兩點，首先XRCC1之T-77C基因多型性是否會增加台灣地區發生肺癌的風險(預測因子)？再則XRCC1之T-77C基因多型性是否與台灣非小細胞肺癌病患之存活率相關(預後因子)？研究方法及材料：本研究共收集294位原發性肺癌病患之腫瘤周邊正常肺組織與288位非癌症者之血液DNA，以PCR-RFLP方式分析T-77C之基因多型性，並利用羅吉斯回歸分析不同基因型之XRCC1 T-77C與肺癌發生之相關性。本研究又以Kaplan-Meier方法統計分析不同基因型之XRCC1 T-77C與肺癌患者預後的相關性。研究結果：結果發現XRCC1 T-77C基因多型性台灣地區肺癌發生之風險並無統計上之顯著差異。但進一步對非小細胞肺癌之存活分析，發現TT 基因型比 TC及CC基因型有較低的存活率(33.1% 比48.8% ; P= 0.031)。另Cox回歸分析亦顯示TT 基因型比 TC及CC基因型非小細胞肺癌病患死亡的機率增加1.84倍(95% CI, 1.16-2.86; P= 0.008)。結論與建議：本研究的結論為XRCC1 T-77C基因變異型TC及CC可作為手術後非小細胞肺癌預後良好之獨立指標。

關鍵字

XRCC1 T77C基因多型性；非小細胞肺癌；預後

並列摘要

Objective：X-ray cross-complementing group 1 (XRCC1) is a base excision repair (BER) gene. There are 17 polymorphisms of XRCC1 been reported. Among these, the association of lung cancer risk and XRCC1 T-77C has been investigated by reduced transcriptional activity of XRCC1 which reduced the DNA repair capacity. A novel T-77C polymorphism in the promoter region of DNA repair gene X-ray cross-complementing group 1 (XRCC1) may modulate its transcription to increase the risk of lung cancer. However, we attempt to clarify: (1) whether the XRCC1 T-77C polymorphism was associated with lung cancer risk in Taiwanese and (2) whether the XRCC1 T-77C polymorphism could act as a prognostic indicator to predict the clinical outcome of non-small-cell lung cancer (NSCLC) patients. Methods and Materials：294 primary lung cancer patients and 288 non-cancer potential controls were recruited into our study. Clinical data were collected. Adjacent normal lung tissues from lung cancer patients and venous bloods from non-cancer control subjects were enrolled for the collection of genomic DNA. Genotyping of the XRCC1 T-77C polymorphism was performed by polymerase chain reaction amplification. An unconditional multiple logistic regression was performed to obtain the odds ratio and 95% confidence interval for each variable between lung cancer cases and control group to understand the association of lung cancer risk. The association of XRCC1 genotypes with patient’s survival was statistically analyzed by Kaplan-Meier method and assessed using a log-rank test for each variable. Subsequently, a multiple Cox regression model was performed to obtain the adjusted hazard ratio and 95% confidence interval for potential prognostic factors in lung cancer patients. Results：Our data showed that the XRCC1 T-77C polymorphism was not associated with the risk of lung cancer in Taiwanese patients. To verify the impact of the XRCC1 T-77C polymorphism on the clinical outcome of NSCLC, survival analysis showed the patients with TT genotype had a lower survival rate than those with the TC+CC genotypes (33.1% versus 48.8%, P= 0.031). The Cox regression analysis further indicated the patients with the TT genotype had a 1.84-fold risk compared with those with the TC + CC genotype (95%CI, 1.16-2.86; P= 0.008). Conclusion and Suggestion：Our results suggest that XRCC1 T-77C variants (TC+CC) may act as a favorable prognostic indicator of resected NSCLC.

並列關鍵字

XRCC1 T77C polymorphism ； NSCLC ； prognosis

參考文獻

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XRCC1 T-77C基因多型性對手術後非小細胞肺癌預後之影響

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