Abstract：
Maternal smoking in pregnancy may increase the risk of testicular germ cell cancer (TGCC) in offspring, but current evidence remains inconclusive. We performed a nested case-control study using cotinine measurements in maternal serum and amniotic fluid as a biomarker for tobacco exposure during pregnancy. A total of 654 males with maternal serum (n = 359, ncases/controls = 71/288) and/or amniotic fluid (n = 295, ncases/controls = 66/229) samples were included. Data on TGCC diagnoses and relevant covariates were derived from nationwide Danish health registries. Cotinine was quantified by liquid chromatography tandem mass spectrometry. An adapted cox regression model estimated the risk of TGCC considering active and inactive tobacco use defined according to cotinine concentrations of <, ≥15 ng/ml. Overall, the concentrations of cotinine were comparable in maternal serum and amniotic fluid (medianserum/amniotic fluid : 2.1/2.6 ng/ml). A strong statistically significant correlation was detected in 14 paired samples (Spearman rho: 0.85). Based on maternal serum cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC in offspring (HR 0.88, 95% CI 0.51; 1.52). Similarly, based on amniotic fluid cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC (HR 1.11, 95% CI 0.64; 1.95). However, different risks were observed for seminomas and nonseminomas in both matrices, but none were statistically significant. Our findings did not provide convincing evidence supporting that exposure to tobacco during pregnancy is associated with TGCC.
摘要：
母亲在怀孕期间吸烟可能会增加后代睾丸生殖细胞癌（TGCC）的风险，但目前的证据还没有定论.我们进行了一项巢式病例对照研究，使用母体血清和羊水中的可替宁测量值作为怀孕期间烟草暴露的生物标志物。总共包括654名男性，其母体血清（n=359，n例/对照=71/288）和/或羊水（n=295，n例/对照=66/229）样本。有关TGCC诊断和相关协变量的数据来自丹麦全国卫生登记处。通过液相色谱串联质谱法定量可替宁。适应的cox回归模型估计了TGCC的风险，考虑了根据可替宁浓度<定义的活性和非活性烟草使用，≥15ng/ml。总的来说,可替宁在母体血清和羊水中的浓度相当(中血清/羊水:2.1/2.6ng/ml).在14个配对样品中检测到强烈的统计学显著相关性(Spearmanrho:0.85)。根据母体血清可替宁浓度，积极使用烟草与后代TGCC风险无关(HR0.88,95%CI0.51;1.52).同样，根据羊水可替宁浓度，主动使用烟草与TGCC风险无关(HR1.11,95%CI0.64;1.95).然而,在两种基质中观察到精原细胞瘤和非精原细胞瘤的风险不同，但没有统计学意义。我们的发现没有提供令人信服的证据支持怀孕期间接触烟草与TGCC相关。
