Breast tumor DNA methylation patterns associated with smoking in the Carolina Breast Cancer Study.
Breast tumor DNA methylation patterns associated with smoking in the Carolina Breast Cancer Study.
复制标题
DOI：
10.1007/s10549-017-4178-8
复制
发表时间：
2017-06
影响因子：
3.8
通讯作者：
Kuan PF
中科院分区：
文献类型：
--
作者：
Conway K;Edmiston SN;Parrish E;Bryant C;Tse CK;Swift-Scanlan T;McCullough LE;Kuan PF
吸烟是几种癌症的危险因素，但它在乳腺癌中作为可能的病因暴露或不良预后因素的作用尚不清楚。DNA甲基化改变有助于乳腺癌的发展，并可能在吸烟和导致癌症发生或进展的基因表达变化之间提供一种机械联系。使用以癌症为重点的阵列，我们在卡罗莱纳乳腺癌研究中检查了517个浸润性乳腺癌中933个CPGS的甲基化，以确定甲基化模式是否因暴露于烟草烟雾而不同。多变量广义线性回归模型被用来比较吸烟者和从不吸烟者之间的肿瘤甲基化情况，总体上或按激素受体(HR)状态分层。在P<；0.05中，与从不吸烟者相比，现在吸烟者或曾经吸烟者的乳腺肿瘤患者的CpG甲基化水平略有不同。在分层分析中，吸烟者的HR−肿瘤与从不吸烟者的肿瘤相比，主要表现为低甲基化；在更均匀的基底样亚型中也同样检测到低甲基化。大多数目前与吸烟相关的CpG基因座在既往吸烟者中表现出甲基化水平，介于现在吸烟者和从不吸烟者之间，并随着吸烟时间的延长表现出甲基化的渐进性变化。在既往吸烟者中，随着戒烟时间的延长，甲基化水平恢复到基线水平(从不吸烟)。此外，在来自黑人的HR+乳腺肿瘤中，吸烟相关的高甲基化比白人更强。我们的结果表明，乳腺癌甲基化模式与吸烟暴露不同；然而，还需要更多的研究来证实这些发现。
Tobacco smoking is a risk factor in several cancers, yet its roles as a putative etiologic exposure or poor prognostic factor in breast cancer are less clear. Altered DNA methylation contributes to breast cancer development and may provide a mechanistic link between smoking and gene expression changes leading to cancer development or progression. Using a cancer-focused array, we examined methylation at 933 CpGs in 517 invasive breast tumors in the Carolina Breast Cancer Study to determine whether methylation patterns differ by exposure to tobacco smoke. Multivariable generalized linear regression models were used to compare tumor methylation profiles between smokers and never smokers, overall, or stratified on hormone receptor (HR) status. Modest differences in CpG methylation were detected at p < 0.05 in breast tumors from current or ever smokers compared with never smokers. In stratified analyses, HR− tumors from smokers exhibited primarily hypomethylation compared with tumors from never smokers; hypomethylation was similarly detected within the more homogeneous basal-like subtype. Most current smoking-associated CpG loci exhibited methylation levels in former smokers that were intermediate between those in current and never smokers and exhibited progressive changes in methylation with increasing duration of smoking. Among former smokers, restoration of methylation toward baseline (never smoking) levels was observed with increasing time since quitting. Moreover, smoking-related hypermethylation was stronger in HR+ breast tumors from blacks than in whites. Our results suggest that breast tumor methylation patterns differ with tobacco smoke exposure; however, additional studies are needed to confirm these findings.
登录
查看更多内容
DOI：
10.1158/1055-9965.epi-15-0874
发表时间：
2016-03
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Allott EH;Cohen SM;Geradts J;Sun X;Khoury T;Bshara W;Zirpoli GR;Miller CR;Hwang H;Thorne LB;O'Connor S;Tse CK;Bell MB;Hu Z;Li Y;Kirk EL;Bethea TN;Perou CM;Palmer JR;Ambrosone CB;Olshan AF;Troester MA
通讯作者：
Troester MA
影响因子：
3.8
作者：
Bardowell, Sabrina A.;Parker, Joel;Fan, Cheng;Crandell, Jamie;Perou, Charles M.;Swift-Scanlan, Theresa
通讯作者：
Swift-Scanlan, Theresa
影响因子：
8.8
作者：
Cooper, J A;Rohan, T E;Cant, E L;Horsfall, D J;Tilley, W D
通讯作者：
Tilley, W D
影响因子：
4.3
作者：
Askari, Marjan;Sobti, Ranbir Chander;Sharma, Suresh C.
通讯作者：
Sharma, Suresh C.
影响因子：
3.8
作者：
Dressler, LG;Geradts, J;Newman, B
通讯作者：
Newman, B