Marcotte Erin L, Druley Todd E, Johnson Kimberly J, Richardson Michaela, von Behren Julie, Mueller Beth A, Carozza Susan, McLaughlin Colleen, Chow Eric J, Reynolds Peggy, Spector Logan G
Division of Epidemiology & Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN.
Masonic Cancer Center, Minneapolis, MN.
Paediatr Perinat Epidemiol. 2017 Nov;31(6):563-572. doi: 10.1111/ppe.12412. Epub 2017 Sep 22.
Infant leukaemia (IL) is extremely rare with fewer than 150 cases occurring each year in the United States. Little is known about its causes. However, recent evidence supports a role of de novo mutations in IL aetiology. Parental age has been associated with several adverse outcomes in offspring, including childhood cancers. Given the role of older parental age in de novo mutations in offspring, we carried out an analysis of parental age and IL.
We evaluated the relationship between parental age and IL in a case-control study using registry data from New York, Minnesota, California, Texas, and Washington. Records from 402 cases [219 acute lymphoblastic leukaemia (ALL), 131 acute myeloid leukaemia (AML), and 52 other] and 45 392 controls born during 1981-2004 were analysed. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression. Estimates were adjusted for infant sex, birth year category, maternal race, state, and mutually adjusted for paternal or maternal age, respectively.
Infants with mothers' age ≥40 years had an increased risk of developing AML (OR 4.80, 95% CI 1.80, 12.76). In contrast, paternal age <20 was associated with increased risk of ALL (OR 3.69, 95% CI 1.62, 8.41).
This study demonstrates increased risk of infant ALL in relation to young paternal age. Given record linkage, there is little concern with recall or selection bias, although data are lacking on MLL gene status and other potentially important variables. Parent of origin effects, de novo mutations, and/or carcinogenic exposures may be involved in IL aetiology.
婴儿白血病(IL)极为罕见,在美国每年发病例数少于150例。其病因鲜为人知。然而,最近的证据支持新发突变在婴儿白血病病因学中起作用。父母年龄与后代的多种不良结局相关,包括儿童期癌症。鉴于父母年龄较大在后代新发突变中的作用,我们对父母年龄与婴儿白血病进行了分析。
我们在一项病例对照研究中,使用纽约、明尼苏达、加利福尼亚、得克萨斯和华盛顿的登记数据,评估了父母年龄与婴儿白血病之间的关系。分析了1981年至2004年期间出生的402例病例[219例急性淋巴细胞白血病(ALL)、131例急性髓细胞白血病(AML)和52例其他类型]以及45392例对照的记录。通过逻辑回归计算比值比(OR)和95%置信区间(CI)。估计值针对婴儿性别、出生年份类别、母亲种族、州进行了调整,并分别针对父亲或母亲年龄进行了相互调整。
母亲年龄≥40岁的婴儿患AML的风险增加(OR 4.80,95%CI 1.80,12.76)。相比之下,父亲年龄<20岁与ALL风险增加相关(OR 3.69,95%CI 1.62,8.41)。
本研究表明父亲年龄较小会增加婴儿患ALL的风险。鉴于记录链接,尽管缺乏MLL基因状态和其他潜在重要变量的数据,但对回忆或选择偏倚几乎无需担忧。起源亲本效应、新发突变和/或致癌暴露可能与婴儿白血病病因学有关。