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課題背景：本研究經(jīng)復旦大學生命科學學院倫理委員會批準,通過對新發(fā)肺癌患者; 無其他器官惡性腫瘤史; 無性別、年齡及病理類型的限制, 共784 例患者作為實驗組。自同一時期相應社區(qū)健康體檢者,其籍貫分布地區(qū)(城鄉(xiāng))、性別、年齡(±5 歲)與病例頻數(shù)匹配, 共782 例作為對照組進行研究。（注：所有人群均為漢族人群）來尋找出染色體8p11(CHRNB3-CHRNA6)區(qū)域基因多態(tài)性與中國漢族人群肺癌易感性的相關(guān)性。 研究方法：通過HapMap 數(shù)據(jù)庫Ⅱ期數(shù)據(jù), 設置最小等位基因頻率(Minor allele frequency, MAF)≥0.05, 關(guān)聯(lián)強度r2≥0.8。來在染色體8p11 區(qū)從42 671 719 bp 到42 742 776 bp共71 kb 區(qū)域內(nèi)選取6 個tag SNP。接下來對樣本進行DNA提取，由上海天昊公司采用連接酶檢測反應(Ligase detectionreaction, LDR)原理進行基因分型。對其進行統(tǒng)計分析（其中應用了卡方檢驗，Haploview軟件，χ2 檢驗，Logistic 回歸）。 研究結(jié)果：rs16891561 位點TT 基因型在60 歲以上人群、女性人群、非吸煙人群中對肺癌發(fā)生具有保護效應; rs4236926 位點TT 基因型在60 歲以上人群、非吸煙人群中對肺癌發(fā)生具有保護效應, 這兩種保護效應主要是與腺癌相關(guān)。并且含有3~4 個變異等位基因型的非吸煙者罹患肺癌的風險顯著降低,含有3~4 個變異等位基因型的個體累計吸煙量與其他個體相比顯著降低。證明人染色體8p11區(qū)域基因多態(tài)性與中國漢族人群肺癌易感性和吸煙行為相關(guān)。 參考文獻： Abstract: To investigate the association between chromosome 8p11 (CHRNB3-CHRNA6) polymorphisms and lung cancersusceptibility in Chinese Han population, we genotyped 6 tag SNPs variants of this region among 784 patients with lungcancer and 782 age- and sex-matched cancer-free control participants to screen for any risk-associated SNPs. The resultsrevealed that rs16891561 TT genotype had a protective effect against lung cancer in people over 60 years old (adjustedOR=0.42, 95% CI=0.20-0.88; P=0.022), female groups (adjusted OR=0.34, 95% CI=0.13-0.87; P=0.025), and non-smokingpeople (adjusted OR=0.32, 95% CI=0.13-079; P=0.013). Additionally, rs4236926 TT genotype had a protective effectagainst lung cancer in people over 60 years old (adjusted OR=0.48, 95% CI=0.23-0.99; P=0.048) and non-smoking people(adjusted OR=0.32, 95% CI=0.13-0.80; P=0.014). According to pathological type of lung cancer, these two SNPs wereassociated with adenocarcinomas susceptibility. As to cumulative effect of rs4236926 and rs16891561, in non-smokersstrata, lung cancer risk was significantly reduced in those who had 3-4 mutant alleles (adjusted OR=0.29, 95% CI=0.11-0.71;P=0.007). Furthermore, people containing 3-4 mutant alleles had lower level of smoking doses (mean pack-year=13.2)compared with others. In conclusion, 8p11 (CHRNB3-CHRNA6) polymorphisms are related to smoking behavior and lung cancer susceptibility in Chinese Han population. Keywords: 8p11; CHRNB3; CHRNA6; single nucleotide polymorphism; lung cancer susceptibility |
