Sklavos Martha M, Zhou Cindy Ke, Pinto Ligia A, Cook Michael B
Human Papillomavirus Immunology Laboratory, Leidos Biomedical Research, Incorporated, Frederick National Laboratory for Cancer Research, Frederick, Maryland.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. Department of Epidemiology and Biostatistics, George Washington University, Washington, District of Columbia.
Cancer Epidemiol Biomarkers Prev. 2014 Nov;23(11):2597-602. doi: 10.1158/1055-9965.EPI-14-0803. Epub 2014 Aug 26.
Despite considerable research, the pathogenesis of prostate cancer remains poorly understood. Meanwhile, PSA testing has shifted prostate cancer case populations for study to include a greater proportion of asymptomatic and indolent disease. Thus, efforts to identify prostate cancer biomarkers-particularly for aggressive disease-are required to elucidate pathogenesis and aid screening efficacy. Current evidence suggests that decreased circulating concentrations of the testis-derived, TGFβ family peptide hormone-anti-Müllerian hormone (AMH)-may be associated with prostate cancer pathogenesis. To test this hypothesis, we measured AMH concentrations in prediagnostic (cohort baseline) sera using the Beckman Coulter AMH Gen II ELISA in 1,000 cases and 1,000 controls nested within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Controls were frequency matched to cases on age at entry, enrollment year, and years of follow-up. Unconditional logistic regression models, adjusted for age at randomization, were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). We found that prediagnostic serologic AMH concentrations were not significantly associated with total (ORQ4 vs. Q1 = 1.15; 95% CI, 0.89-1.48; Ptrend = 0.13), aggressive (ORQ4 vs. Q1 = 1.14; 95% CI, 0.80-1.63; Ptrend = 0.51), or nonaggressive (ORQ4 vs. Q1 = 1.22; 95% CI, 0.91-1.63; Ptrend = 0.07) prostate cancer risks. Different definitions of aggressive disease did not meaningfully alter these results. Despite in vitro studies linking AMH to prostate cancer, this first analysis of prediagnostic, circulating AMH concentrations in men provides no evidence for an association with prostate cancer risk.
尽管进行了大量研究，但前列腺癌的发病机制仍未得到充分了解。与此同时，前列腺特异性抗原（PSA）检测已改变了前列腺癌病例的研究人群，使其包括更大比例的无症状和惰性疾病患者。因此，需要努力寻找前列腺癌生物标志物，尤其是侵袭性疾病的生物标志物，以阐明发病机制并提高筛查效果。目前的证据表明，睾丸来源的转化生长因子β（TGFβ）家族肽激素——抗苗勒管激素（AMH）的循环浓度降低可能与前列腺癌发病机制有关。为了验证这一假设，我们在前列腺、肺、结直肠癌和卵巢癌（PLCO）筛查试验中的1000例病例和1000例对照中，使用贝克曼库尔特AMH Gen II酶联免疫吸附测定法（ELISA）测量了诊断前（队列基线）血清中的AMH浓度。对照在入组年龄、入组年份和随访年限方面与病例进行频率匹配。使用针对随机分组时年龄进行调整的无条件逻辑回归模型来估计比值比（OR）和95%置信区间（95%CI）。我们发现，诊断前血清AMH浓度与总体前列腺癌风险（OR Q4与Q1 = 1.15；95%CI，0.89 - 1.48；P趋势 = 0.13）、侵袭性前列腺癌风险（OR Q4与Q1 = 1.14；95%CI，0.80 - 1.63；P趋势 = 0.51）或非侵袭性前列腺癌风险（OR Q4与Q1 = 1.22；95%CI，0.91 - 1.63；P趋势 = 0.07）均无显著关联。对侵袭性疾病的不同定义并未显著改变这些结果。尽管体外研究将AMH与前列腺癌联系起来，但这项对男性诊断前循环AMH浓度的首次分析并未提供AMH与前列腺癌风险相关的证据。
