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課題背景：本研究經(jīng)復(fù)旦大學(xué)生命科學(xué)學(xué)院倫理委員會(huì)批準(zhǔn),通過(guò)對(duì)新發(fā)肺癌患者; 無(wú)其他器官惡性腫瘤史; 無(wú)性別、年齡及病理類型的限制, 共784 例患者作為實(shí)驗(yàn)組。自同一時(shí)期相應(yīng)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(duì)照組進(jìn)行研究。（注：所有人群均為漢族人群）來(lái)尋找出染色體8p11(CHRNB3-CHRNA6)區(qū)域基因多態(tài)性與中國(guó)漢族人群肺癌易感性的相關(guān)性。 研究方法：通過(guò)HapMap 數(shù)據(jù)庫(kù)Ⅱ期數(shù)據(jù), 設(shè)置最小等位基因頻率(Minor allele frequency, MAF)≥0.05, 關(guān)聯(lián)強(qiáng)度r2≥0.8。來(lái)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(gè)tag SNP。接下來(lái)對(duì)樣本進(jìn)行DNA提取，由上海天昊公司采用連接酶檢測(cè)反應(yīng)(Ligase detectionreaction, LDR)原理進(jìn)行基因分型。對(duì)其進(jìn)行統(tǒng)計(jì)分析（其中應(yīng)用了卡方檢驗(yàn)，Haploview軟件，χ2 檢驗(yàn)，Logistic 回歸）。 研究結(jié)果：rs16891561 位點(diǎn)TT 基因型在60 歲以上人群、女性人群、非吸煙人群中對(duì)肺癌發(fā)生具有保護(hù)效應(yīng); rs4236926 位點(diǎn)TT 基因型在60 歲以上人群、非吸煙人群中對(duì)肺癌發(fā)生具有保護(hù)效應(yīng), 這兩種保護(hù)效應(yīng)主要是與腺癌相關(guān)。并且含有3~4 個(gè)變異等位基因型的非吸煙者罹患肺癌的風(fēng)險(xiǎn)顯著降低,含有3~4 個(gè)變異等位基因型的個(gè)體累計(jì)吸煙量與其他個(gè)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(guó)漢族人群肺癌易感性和吸煙行為相關(guān)。 參考文獻(xiàn)： 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 |
