دورية أكاديمية
Differential DNA methylation in blood as a mediator of the association between cigarette smoking and bladder cancer risk among postmenopausal women
| العنوان: | Differential DNA methylation in blood as a mediator of the association between cigarette smoking and bladder cancer risk among postmenopausal women |
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| المؤلفون: | Kristina M. Jordahl, Amanda I. Phipps, Timothy W. Randolph, Hilary A. Tindle, Simin Liu, Lesley F. Tinker, Karl T. Kelsey, Emily White, Parveen Bhatti |
| المصدر: | Epigenetics, Vol 14, Iss 11, Pp 1065-1073 (2019) |
| بيانات النشر: | Taylor & Francis Group, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Genetics |
| مصطلحات موضوعية: | cigarette smoking, dna methylation, bladder cancer, aryl-hydrocarbon receptor repressor gene (ahrr), g protein-coupled receptor 15 gene (gpr15), f2r like thrombin or trypsin receptor 3 gene (f2rl3), Genetics, QH426-470 |
| الوصف: | Smoking accounts for approximately 52% of bladder cancer incidence among postmenopausal women, but the underlying mechanism is poorly understood. Our study investigates whether changes in DNA methylation, as measured in blood, mediate the impact of smoking on bladder cancer risk among postmenopausal women. We conducted analyses among 206 cases and 251 controls that were current or never smokers at baseline from a previous case-control study of bladder cancer and genome-wide DNA methylation nested within the Women’s Health Initiative. Separate mediation analyses were conducted for three CpG sites demonstrating robust associations with smoking in prior methylome-wide association studies: cg05575921 (AhRR), cg03636183 (F2RL3), and cg19859270 (GPR15). We estimated causal effects using the regression-based, four-way decomposition approach, which addresses the interaction between smoking and each CpG site. The overall proportion of the excess relative risk mediated by cg05575921 was 92% (p-value = 0.004) and by cg19859270 was 79% (p-value = 0.02). The largest component of the excess relative risk of bladder cancer due to 30 pack-years of smoking history in current smokers was the mediated interaction for both cg05575921 (72%, p = 0.02) and cg19859270 (72%, p-value = 0.04), where the mediated interaction is the effect of smoking on bladder cancer that both acts through differential methylation and depends on smoking history. There was little evidence that smoking was mediated through cg03636183. Our results suggest that differential methylation of cg05575921 and cg19859270 mediate the effects of smoking on bladder cancer, potentially revealing downstream effects of smoking relevant for carcinogenesis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1559-2294 1559-2308 15592294 |
| العلاقة: | https://doaj.org/toc/1559-2294Test; https://doaj.org/toc/1559-2308Test |
| DOI: | 10.1080/15592294.2019.1631112 |
| الوصول الحر: | https://doaj.org/article/5d29b3f6b3fa44ac9bbd56d61c101952Test |
| رقم الانضمام: | edsdoj.5d29b3f6b3fa44ac9bbd56d61c101952 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15592294 15592308 |
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| DOI: | 10.1080/15592294.2019.1631112 |