Cancer Research UK Institute for Cancer Studies, School of Cancer Sciences, University of Birmingham, Birmingham, Edgbaston, B15 2TT, UK.
Br J Cancer. 2011 Apr 26;104(9):1500-4. doi: 10.1038/bjc.2011.113. Epub 2011 Apr 12.
To prove a causal link between an epigenetic change and an environmental or behavioural risk factor for a given disease, it is first necessary to show that the onset of exposure precedes the first detection of that epigenetic change in subjects who are still free of disease.
Towards this end, a cohort of women aged 15-19 years, recruited soon after they first had sexual intercourse, were used to provide sequential observations on the relationship between cigarette smoking and the detection in cervical cytological samples of methylated forms of CDKN2A (p16) using nested methylation-specific polymerase chain reaction.
Among women who remained cytologically normal and who tested negative for human papillomavirus DNA in cervical smears during follow-up, those who first started to smoke during follow-up had an increased risk of acquiring CDKN2A methylation compared with never-smokers (odds ratio=3.67; 95% confidence interval 1.09-12.33; P=0.04).
Smoking initiation is associated with the appearance of methylated forms of CDKN2A.
要证明表观遗传变化与特定疾病的环境或行为风险因素之间存在因果关系，首先需要证明在仍未患病的受试者中，暴露的开始先于该表观遗传变化的首次检测。
为此，使用了一组年龄在 15-19 岁的女性队列，她们在首次发生性行为后不久就被招募，用于提供关于吸烟与宫颈细胞学样本中 CDKN2A（p16）甲基化形式检测之间关系的序贯观察，使用巢式甲基化特异性聚合酶链反应。
在细胞学正常且宫颈涂片 HPV DNA 检测阴性的女性中，与从不吸烟者相比，在随访期间首次开始吸烟的女性获得 CDKN2A 甲基化的风险增加（比值比=3.67；95%置信区间 1.09-12.33；P=0.04）。
吸烟开始与 CDKN2A 甲基化形式的出现有关。
