Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.
Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.
Int J Epidemiol. 2021 Mar 3;50(1):105-115. doi: 10.1093/ije/dyaa210.
Prenatal exposure to maternal smoking is detrimental to child health but its association with risk of cancer has seldom been investigated. Maternal smoking induces widespread and long-lasting DNA methylation changes, which we study here for association with risk of cancer in adulthood.
Eight prospective case-control studies nested within the Melbourne Collaborative Cohort Study were used to assess associations between maternal-smoking-associated methylation marks in blood and risk of several cancers: breast (n = 406 cases), colorectal (n = 814), gastric (n = 166), kidney (n = 139), lung (n = 327), prostate (n = 847) and urothelial (n = 404) cancer and B-cell lymphoma (n = 426). We used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between cancer and five methylation scores calculated as weighted averages for 568, 19, 15, 28 and 17 CpG sites. Models were adjusted for confounders, including personal smoking history (smoking status, pack-years, age at starting and quitting) and methylation scores for personal smoking.
All methylation scores for maternal smoking were strongly positively associated with risk of urothelial cancer. Risk estimates were only slightly attenuated after adjustment for smoking history, other potential confounders and methylation scores for personal smoking. Potential negative associations were observed with risk of lung cancer and B-cell lymphoma. No associations were observed for other cancers.
We found that methylation marks of prenatal exposure to maternal smoking are associated with increased risk of urothelial cancer. Our study demonstrates the potential for using DNA methylation to investigate the impact of early-life, unmeasured exposures on later-life cancer risk.
母亲在怀孕期间吸烟对儿童健康有害，但很少有研究调查其与癌症风险的关系。母亲吸烟会引起广泛而持久的 DNA 甲基化变化，我们在这里研究这些变化与成年后患癌症的风险之间的关系。
我们使用墨尔本合作队列研究中的 8 项前瞻性病例对照研究，评估血液中与母亲吸烟相关的甲基化标记物与多种癌症风险之间的关联：乳腺癌（n=406 例）、结直肠癌（n=814 例）、胃癌（n=166 例）、肾癌（n=139 例）、肺癌（n=327 例）、前列腺癌（n=847 例）和膀胱癌（n=404 例）和 B 细胞淋巴瘤（n=426 例）。我们使用条件逻辑回归模型来估计癌症与五个甲基化评分之间的比值比（OR）和 95%置信区间（CI），这些评分是通过对 568、19、15、28 和 17 个 CpG 位点的加权平均值计算得出的。模型调整了混杂因素，包括个人吸烟史（吸烟状况、吸烟年数、开始和戒烟年龄）和个人吸烟的甲基化评分。
所有与母亲吸烟相关的甲基化评分均与膀胱癌风险呈强烈正相关。在调整了吸烟史、其他潜在混杂因素和个人吸烟的甲基化评分后，风险估计值略有降低。与肺癌和 B 细胞淋巴瘤的风险呈负相关。未观察到与其他癌症的关联。
我们发现，母亲吸烟的产前暴露甲基化标记物与膀胱癌风险增加有关。我们的研究表明，使用 DNA 甲基化来研究早期未被测量的暴露对晚年癌症风险的影响具有潜力。
