AHRR methylation in heavy smokers: associations with smoking, lung cancer risk, and lung cancer mortality.
AHRR methylation in heavy smokers: associations with smoking, lung cancer risk, and lung cancer mortality.
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DOI：
10.1186/s12885-020-07407-x
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发表时间：
2020-09-22
期刊：
影响因子：
3.8
通讯作者：
Doherty JA
中科院分区：
文献类型：
--
作者：
Grieshober L;Graw S;Barnett MJ;Thornquist MD;Goodman GE;Chen C;Koestler DC;Marsit CJ;Doherty JA
芳香烃受体阻遏物（AHRR）基因中cg 05575921的低水平甲基化与吸烟密切相关，一些研究已经观察到cg 05575921甲基化与肺癌风险和死亡率增加之间的相关性。为了前瞻性地研究cg 05575921甲基化降低是否可以识别重度吸烟者肺癌筛查的高风险亚群，以及病例的死亡率，我们评估了cg 05575921甲基化与重度吸烟者肺癌风险和死亡率之间的相关性。β-胡萝卜素和视黄醇疗效试验（CARET）纳入了年龄在45-69岁之间、有≥ 20包年吸烟史和/或职业石棉暴露的入组者。CARET参与者的一个子集具有cg 05575921甲基化，其可从病例中肺癌诊断前平均4.3年收集的血液的HumanMethylationEPIC测定中获得。连续处理Cg 05575921甲基化β值，甲基化降低10%，并作为五分位数，其中五分位数1（Q1，参考）代表高甲基化，Q5代表低甲基化。我们在一项巢式病例对照研究中使用条件logistic回归模型来检查肺癌的总体风险和组织型风险，该研究包括316例肺癌病例（诊断至2005年）和316例无肺癌对照，年龄（±5岁），性别，种族/民族，入组年份，当前/既往吸烟，石棉暴露和随访时间匹配。死亡率分析包括1985年至2013年间诊断的372例肺癌病例，这些病例具有可用的甲基化数据。我们使用考克斯比例风险模型来检查总体死亡率和组织型死亡率。cg 05575921甲基化的降低与吸烟密切相关，即使在我们的重度吸烟人群中也是如此。我们没有观察到诊断前cg 05575921甲基化降低与肺癌风险增加之间的相关性，无论是整体还是组织型。我们观察到腺癌和小细胞癌cg 05575921甲基化五分位数下降时肺癌特异性死亡率呈线性增加趋势（P趋势分别= 0.01和0.04）。在我们对重度吸烟者的研究中，cg 05575921甲基化的降低与吸烟密切相关，但与肺癌风险无关。观察到的cg 05575921甲基化与腺癌和小细胞组织型死亡率增加之间的相关性需要进一步研究。我们的研究结果不支持使用降低的cg 05575921甲基化作为肺癌筛查风险分层的生物标志物。
A low level of methylation at cg05575921 in the aryl-hydrocarbon receptor repressor (AHRR) gene is robustly associated with smoking, and some studies have observed associations between cg05575921 methylation and increased lung cancer risk and mortality. To prospectively examine whether decreased methylation at cg05575921 may identify high risk subpopulations for lung cancer screening among heavy smokers, and mortality in cases, we evaluated associations between cg05575921 methylation and lung cancer risk and mortality, by histotype, in heavy smokers. The β-Carotene and Retinol Efficacy Trial (CARET) included enrollees ages 45–69 with ≥ 20 pack-year smoking histories and/or occupational asbestos exposure. A subset of CARET participants had cg05575921 methylation available from HumanMethylationEPIC assays of blood collected on average 4.3 years prior to lung cancer diagnosis in cases. Cg05575921 methylation β-values were treated continuously for a 10% methylation decrease and as quintiles, where quintile 1 (Q1, referent) represents high methylation and Q5, low methylation. We used conditional logistic regression models to examine lung cancer risk overall and by histotype in a nested case-control study including 316 lung cancer cases (diagnosed through 2005) and 316 lung cancer-free controls matched on age (±5 years), sex, race/ethnicity, enrollment year, current/former smoking, asbestos exposure, and follow-up time. Mortality analyses included 372 lung cancer cases diagnosed between 1985 and 2013 with available methylation data. We used Cox proportional hazards models to examine mortality overall and by histotype. Decreased cg05575921 methylation was strongly associated with smoking, even in our population of heavy smokers. We did not observe associations between decreased pre-diagnosis cg05575921 methylation and increased lung cancer risk, overall or by histotype. We observed linear increasing trends for lung cancer-specific mortality across decreasing cg05575921 methylation quintiles for adenocarcinoma and small cell carcinoma (P-trends = 0.01 and 0.04, respectively). In our study of heavy smokers, decreased cg05575921 methylation was strongly associated with smoking but not increased lung cancer risk. The observed association between cg05575921 methylation and increased mortality in adenocarcinoma and small cell histotypes requires further examination. Our results do not support using decreased cg05575921 methylation as a biomarker for lung cancer screening risk stratification.
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影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
影响因子：
5.8
作者：
de Vries M;van der Plaat DA;Nedeljkovic I;Verkaik-Schakel RN;Kooistra W;Amin N;van Duijn CM;Brandsma CA;van Diemen CC;Vonk JM;Marike Boezen H
通讯作者：
Marike Boezen H
影响因子：
39.2
作者：
Moyer, Virginia A.
通讯作者：
Moyer, Virginia A.
影响因子：
11.1
作者：
McCartney DL;Stevenson AJ;Hillary RF;Walker RM;Bermingham ML;Morris SW;Clarke TK;Campbell A;Murray AD;Whalley HC;Porteous DJ;Visscher PM;McIntosh AM;Evans KL;Deary IJ;Marioni RE
通讯作者：
Marioni RE
DOI：
10.1093/jnci/djh320
发表时间：
2004-12-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Goodman, GE;Thornquist, MD;Williams, JH
通讯作者：
Williams, JH