Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK.
Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, Oslo, Norway.
Andrology. 2017 Sep;5(5):914-922. doi: 10.1111/andr.12388. Epub 2017 Aug 13.
Observational studies have suggested anthropometric traits, particularly increased height are associated with an elevated risk of testicular cancer (testicular germ cell tumour). However, there is an inconsistency between study findings, suggesting the possibility of the influence of confounding factors. To examine the association between anthropometric traits and testicular germ cell tumour using an unbiased approach, we performed a Mendelian randomisation study. We used genotype data from genome wide association studies of testicular germ cell tumour totalling 5518 cases and 19,055 controls. Externally weighted polygenic risk scores were created and used to evaluate associations with testicular germ cell tumour risk per one standard deviation (s.d) increase in genetically-defined adult height, adult BMI, adult waist hip ratio adjusted for BMI (WHRadjBMI), adult hip circumference adjusted for BMI (HIPadjBMI), adult waist circumference adjusted for BMI (WCadjBMI), birth weight (BW) and childhood obesity. Mendelian randomisation analysis did not demonstrate an association between any anthropometric trait and testicular germ cell tumour risk. In particular, despite good power, there was no global evidence for association between height and testicular germ cell tumour. However, three SNPs for adult height individually showed association with testicular germ cell tumour (rs4624820: OR = 1.47, 95% CI: 1.41-1.55, p = 2.7 × 10 ; rs12228415: OR = 1.17, 95% CI: 1.11-1.22, p = 3.1 × 10 ; rs7568069: OR = 1.13, 95% CI: 1.07-1.18, p = 1.1 × 10 ). This Mendelian randomisation analysis, based on the largest testicular germ cell tumour genome wide association dataset to date, does not support a causal etiological association between anthropometric traits and testicular germ cell tumour aetiology. Our findings are more compatible with confounding by shared environmental factors, possibly related to prenatal growth with exposure to these risk factors occurring in utero.
观察性研究表明，人体测量特征，特别是身高增加与睾丸癌（睾丸生殖细胞肿瘤）风险升高有关。然而，研究结果之间存在不一致性，表明可能存在混杂因素的影响。为了使用无偏倚的方法研究人体测量特征与睾丸生殖细胞肿瘤之间的关联，我们进行了一项孟德尔随机化研究。我们使用了总计 5518 例病例和 19055 例对照的睾丸生殖细胞肿瘤全基因组关联研究的基因型数据。创建了外部加权多基因风险评分，并用于评估每个标准偏差（s.d）增加遗传定义的成人身高、成人 BMI、BMI 校正的成人腰臀比（WHRadjBMI）、BMI 校正的成人臀围（HIPadjBMI）、BMI 校正的成人腰围（WCadjBMI）、出生体重（BW）和儿童肥胖与睾丸生殖细胞肿瘤风险之间的关联。孟德尔随机化分析表明，任何人体测量特征与睾丸生殖细胞肿瘤风险之间都没有关联。特别是，尽管具有很好的功效，但身高与睾丸生殖细胞肿瘤之间没有全球关联的证据。然而，三个成人身高的 SNP 单独与睾丸生殖细胞肿瘤相关（rs4624820：OR=1.47，95%CI：1.41-1.55，p=2.7×10；rs12228415：OR=1.17，95%CI：1.11-1.22，p=3.1×10；rs7568069：OR=1.13，95%CI：1.07-1.18，p=1.1×10）。这项基于迄今为止最大的睾丸生殖细胞肿瘤全基因组关联数据集的孟德尔随机化分析，不支持人体测量特征与睾丸生殖细胞肿瘤病因学之间存在因果关系。我们的研究结果更符合共同环境因素的混杂，可能与产前生长有关，这些危险因素在子宫内暴露。
