據(jù)4月25日發(fā)表在National Cancer Institute雜志上的一項(xiàng)研究證實(shí)：rs1051730-rs16969968基因型和煙草暴露之間的關(guān)系引發(fā)了患肺癌風(fēng)險(xiǎn)增高。
rs1051730-rs16969968基因型與吸煙,、肺癌以及其他與吸煙有關(guān)的后果有一定聯(lián)系。此前的研究一般依靠吸煙者對(duì)吸煙行為的自我報(bào)告,，這可能低估了并掩蓋了吸煙對(duì)肺癌和其他健康結(jié)果這些多態(tài)性疾病的貢獻(xiàn)。
布里斯托爾大學(xué)實(shí)驗(yàn)心理學(xué)博士Marcus R. Munafò和他的同事從六個(gè)獨(dú)立的研究中考察自我報(bào)告的卷煙消費(fèi)量和血漿或血清中可鐵寧水平之間的關(guān)聯(lián),，確定了rs1051730-rs16969968基因型與肺癌風(fēng)險(xiǎn)之間的聯(lián)系,。此外，研究者使用已經(jīng)發(fā)表的數(shù)據(jù)分析了可替寧水平與肺癌風(fēng)險(xiǎn)之間的聯(lián)系,，探討了基因型與肺癌風(fēng)險(xiǎn)之間的關(guān)系,。
研究人員通過測(cè)量可替寧水平發(fā)現(xiàn)rs1051730-rs16969968基因型與煙草暴露強(qiáng)烈有關(guān)。這些數(shù)據(jù)支持rs1051730-rs16969968基因型與肺癌風(fēng)險(xiǎn)的關(guān)系主要是有煙草暴露引起的,。然而研究人員指出,，這項(xiàng)研究還存在某些限制如數(shù)據(jù)來自不同研究的不同人群等。（生物谷：Bioon.com）
doi:10.1093/jnci/djs191
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PMID:
Association Between Genetic Variants on Chromosome 15q25 Locus and Objective Measures of Tobacco Exposure
Marcus R. Munafò, Maria N. Timofeeva, Richard W. Morris, David Prieto-Merino, Naveed Sattar, Paul Brennan, et al.
Background 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.
Methods 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.
Results 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).
Conclusions 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.
