Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure.
Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure.
复制标题
在15q25染色体上的遗传变异与烟草暴露的客观度量之间的关联。
DOI：
10.1093/jnci/djs191
复制
发表时间：
2012-05-16
期刊：
影响因子：
--
通讯作者：
Davey Smith G
中科院分区：
文献类型：
--
作者：
Munafò MR;Timofeeva MN;Morris RW;Prieto-Merino D;Sattar N;Brennan P;Johnstone EC;Relton C;Johnson PC;Walther D;Whincup PH;Casas JP;Uhl GR;Vineis P;Padmanabhan S;Jefferis BJ;Amuzu A;Riboli E;Upton MN;Aveyard P;Ebrahim S;Hingorani AD;Watt G;Palmer TM;Timpson NJ;EPIC Study Group;Davey Smith G
两个单核苷酸多态性rs1051730和rs16969968位于染色体15q25位点的烟碱乙酰胆碱受体基因簇中，与吸烟严重程度、肺癌风险和其他吸烟相关的健康结果有关。以前的研究通常依赖于自我报告的吸烟行为，这可能无法完全捕捉到烟草暴露的个体差异。我们研究了rs1051730和rs16969968基因型（被称为rs1051730 - rs16969968，因为它们是完美的连锁不平衡和可互换的）与吸烟者自我报告的每日卷烟消费量和生化测量的血浆或血清可替宁水平的关系。从6项独立研究中获得了12364名受试者的汇总估计和描述性统计数据，其中包括2932名吸烟者。采用线性回归方法计算每项研究中rs1051730-rs16969968基因型与当前吸烟者的卷烟消费和可替宁水平的每等位基因相关性。采用随机效应法对每等位基因关联进行meta分析。基因型和肺癌风险之间可能产生的关联使用可替宁水平和肺癌风险之间的关联的已发表数据进行了评估。所有统计检验均为双侧检验。合并的每等位基因关联显示，携带一个或两个rs1051730-rs16969968风险等位基因拷贝的当前吸烟者增加了自我报告的卷烟量（每个等位基因每天未调整的卷烟数平均增加= 1.0支，95%可信区间[CI] = 0.57至1.43支，P = 5.22 × 10−6）和可替宁水平（每个等位基因未调整的可替宁水平平均增加= 138.72 nmol/L, 95% CI = 97.91至179.53 nmol/L, P = 2.71 × 10−11）。可替宁水平的增加表明，rs1051730-rs16969968风险等位基因每增加一个拷贝，肺癌的风险就会增加（每等位基因优势比= 1.31,95% CI = 1.21至1.42）。我们的数据显示，与自我报告的卷烟消费相比，rs1051730-rs16969968基因型与烟草暴露的客观测量有更强的关联。这些变异与肺癌风险的关联，如果不是全部，也可能主要是通过烟草暴露介导的。
Two single-nucleotide polymorphisms, rs1051730 and rs16969968, located within the nicotinic acetylcholine receptor gene cluster on chromosome 15q25 locus, are associated with heaviness of smoking, risk for lung cancer, and other smoking-related health outcomes. Previous studies have typically relied on self-reported smoking behavior, which may not fully capture interindividual variation in tobacco exposure. We investigated the association of rs1051730 and rs16969968 genotype (referred to as rs1051730–rs16969968, because these are in perfect linkage disequilibrium and interchangeable) with both self-reported daily cigarette consumption and biochemically measured plasma or serum cotinine levels among cigarette smokers. Summary estimates and descriptive statistical data for 12 364 subjects were obtained from six independent studies, and 2932 smokers were included in the analyses. Linear regression was used to calculate the per-allele association of rs1051730–rs16969968 genotype with cigarette consumption and cotinine levels in current smokers for each study. Meta-analysis of per-allele associations was conducted using a random effects method. The likely resulting association between genotype and lung cancer risk was assessed using published data on the association between cotinine levels and lung cancer risk. All statistical tests were two-sided. Pooled per-allele associations showed that current smokers with one or two copies of the rs1051730–rs16969968 risk allele had increased self-reported cigarette consumption (mean increase in unadjusted number of cigarettes per day per allele = 1.0 cigarette, 95% confidence interval [CI] = 0.57 to 1.43 cigarettes, P = 5.22 × 10−6) and cotinine levels (mean increase in unadjusted cotinine levels per allele = 138.72 nmol/L, 95% CI = 97.91 to 179.53 nmol/L, P = 2.71 × 10−11). The increase in cotinine levels indicated an increased risk of lung cancer with each additional copy of the rs1051730–rs16969968 risk allele (per-allele odds ratio = 1.31, 95% CI = 1.21 to 1.42). Our data show a stronger association of rs1051730–rs16969968 genotype with objective measures of tobacco exposure compared with self-reported cigarette consumption. The association of these variants with lung cancer risk is likely to be mediated largely, if not wholly, via tobacco exposure.
登录
查看更多内容
影响因子：
3.8
作者：
Hammond, David;Fong, Geoffrey T.;McNeill, Ann
通讯作者：
McNeill, Ann
影响因子：
7.7
作者：
Freathy RM;Kazeem GR;Morris RW;Johnson PC;Paternoster L;Ebrahim S;Hattersley AT;Hill A;Hingorani AD;Holst C;Jefferis BJ;Kring SI;Mooser V;Padmanabhan S;Preisig M;Ring SM;Sattar N;Upton MN;Vollenweider P;Waeber G;Sørensen TI;Frayling TM;Watt G;Lawlor DA;Whincup PH;Tozzi F;Davey Smith G;Munafò M
通讯作者：
Munafò M
DOI：
10.1016/0197-2456(86)90046-2
发表时间：
1986-09-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
DERSIMONIAN, R;LAIRD, N
通讯作者：
LAIRD, N
影响因子：
11.2
作者：
Broderick P;Wang Y;Vijayakrishnan J;Matakidou A;Spitz MR;Eisen T;Amos CI;Houlston RS
通讯作者：
Houlston RS
影响因子：
3.5
作者：
Keskitalo, Kaisu;Broms, Ulla;Kaprio, Jaakko
通讯作者：
Kaprio, Jaakko