CDKN2B-AS1基因多型性及環境因子對肺癌易感性之影響

肺癌的形成主要分為小細胞肺癌 (small cell lung cancer, SCLC) 與非小細胞肺癌 (non-small cell lung cancer, NSCLC)，NSCLC組織型態分類為腺癌 (adenocarcinoma)、鱗狀細胞癌 (Squamous-cell carcinoma)與大細胞肺癌 (Large cell lung carcinoma, LCC)，此外腺癌的形成原因與DNA突變或缺失有關。根據衛生福利部109年十大死因統計，在台灣每十萬人口中約有40.8人死於肺癌。因此肺癌在台灣為死亡率及癌症類別佔比最高的疾病。根據全基因組關聯分析 (Genome-wide association study, GAWS) 的資料顯示CDKN2B-AS1位於CDKN2A/B基因座的 9p21.3，此長鏈非編碼RNA (Long non-coding RNA, LncRNA) 其單核苷酸多型性變異與許多疾病或癌症相關，因此我們針對LncRNA CDKN2B-AS1中的基因多型性rs2151280、rs1537373、rs1333048、rs8181047、rs564398與環境因子的相關性探討對肺腺癌易感性之影響。本論文共收集275位肺腺癌患者，包含125位男性與150位女性，平均年齡約為65歲，將檢體收集並且分離血漿後，將DNA萃取並且以分光光度計標定濃度並保存。分析CDKN2B-AS1之基因多型性，rs2151280、rs1537373、rs1333048、rs8181047、rs564398與肺腺癌患者之相關性。研究結果發現，CDKN2B-AS1基因多型性在表皮生長因子 (Epidermal growth factor receptor, EGFR) 突變與否的肺癌個案皆無顯著相關，但進一步分析發現，CDKN2B-AS1 rs564398攜帶TC+CC的變異在腫瘤大小的結果對於EGFR未突變的肺腺癌患者有顯著差異。因此我們的研究結果顯示在CDKN2B-AS1之基因多型性rs564398對於腫瘤的進展似乎有較小的風險形成較大的腫瘤 (T3+T4)。CDKN2B-AS1單核苷酸多型性或許可以做為預測肺腺癌病程進展與預後的腫瘤標記。

關鍵字

肺癌；表皮生長因子；單核苷酸多態性

並列摘要

The formation of lung cancer is mainly divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Squamous-cell carcinoma) and large cell lung carcinoma (LCC), and the formation of adenocarcinoma is related to DNA mutation or deletion.According to the statistics of the top ten causes of death in 2020 by the ministry of Health and Welfare of Taiwan, about 40.8 people died of trachea, bronchus and lung cancer per 100,000 popμLations. Therefore, lung cancer is the disease with the highest mortality rate and cancer category in Taiwan. According to the Genome-wide association study (GAWS) indicated that CDKN2B-AS1 is located at 9p21.3 of the CDKN2A/B locus, and the single-nucleotide polymorphism of this long non-coding RNA is associated with many diseases or cancers. Thus, we targeted lncRNA CDKN2B-AS1 rs2151280, rs1537373, rs1333048, rs8181047, rs564398 and environmental factors in and their effects on the susceptibility of lung adenocarcinoma. A total of 275 lung adenocarcinoma patients, including 125 males and 150 females, with an average age of about 65 years old, were collected. The CDKN2B-AS1 rs2151280, rs1537373, rs1333048, rs8181047, rs564398 were analysed with real-time polymerase chain reaction. Our resμLts demonstrated that the presence of at least one C genotype (TC and CC) allele on CDKN2B-AS1 rs564398 was exhibited significant associations with the size of primary tumors in lung adenocarcinoma patients with the EGFR wild type. CDKN2B-AS1 single nucleotide polytypes may be used as tumor markers to predict the progression and prognosis of lung adenocarcinoma.Our resμLts show that the genotype of rs564398 in CDKN2B-AS1 appears to have a lower risk for tumor progression to form larger tumors (T3+T4). CDKN2B-AS1 single nucleotide polytypes may be used as tumor markers to predict the progression and prognosis of lung adenocarcinoma.

並列關鍵字

lung cancer ； SNP ； EGFR ； LncRNA ； CDKN2B-AS1 ； ANRIL

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