循环白细胞端粒长度与总体及侵袭性前列腺癌风险
Circulating leukocyte telomere length and risk of overall and aggressive prostate cancer.
作者信息
Julin B, Shui I, Heaphy C M, Joshu C E, Meeker A K, Giovannucci E, De Vivo I, Platz E A
机构信息
1] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA [2] Department of Epidemiology, Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, MA, USA [3] Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
出版信息
Br J Cancer. 2015 Feb 17;112(4):769-76. doi: 10.1038/bjc.2014.640. Epub 2015 Jan 6.
BACKGROUND
Recent large-scale prospective studies suggest that long telomeres are associated with an increase cancer risk, counter to conventional wisdom.
METHODS
To further clarify the association between leukocyte telomere length (LTL) and prostate cancer, and assess genetic variability in relation to both LTL and prostate cancer, we performed a nested case-control study (922 cases and 935 controls). The participants provided blood in 1993-1995 and were followed through August 2004 (prostate cancer incidence) or until 28 February 2013 (lethal or fatal prostate cancer). Relative LTL was measured by quantitative PCR and was calculated as the ratio of telomere repeat copy number to a single gene (36B4) copy number (T/S). Genotyping was performed using the TaqMan OpenArray SNP Genotyping Platform. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of all prostate cancer and subtypes defined by Gleason grade, stage and lethality (metastasis or death).
RESULTS
We observed a positive association between each s.d. increase in LTL and all (multivariable-adjusted OR 1.11, 95% CI: 1.01-1.22), low-grade (OR 1.13, 95% CI:1.01-1.27), and localised (OR 1.12, 95% CI:1.01-1.24) prostate cancer. Associations for other subtypes were similar, but did not reach statistical significance. In subgroup analyses, associations for high grade and advanced stage (OR=2.04, 95% CI 1.00-4.17; Pinteraction=0.06) or lethal disease (OR=2.37, 95% CI 1.19-4.72; Pinteraction=0.01) were stronger in men with a family history of the disease compared with those without. The minor allele of SNP, rs7726159, which has previously been shown to be positively associated with LTL, showed an inverse association with all prostate cancer risk after correction for multiple testing (P=0.0005).
CONCLUSION
In this prospective study, longer LTL was modestly associated with higher risk of prostate cancer. A stronger association for more aggressive cancer in men with a family history of the disease needs to be confirmed in larger studies.
背景
近期大规模前瞻性研究表明，与传统认知相反，长端粒与癌症风险增加相关。
方法
为进一步阐明白细胞端粒长度（LTL）与前列腺癌之间的关联，并评估与LTL和前列腺癌相关的基因变异性，我们开展了一项巢式病例对照研究（922例病例和935例对照）。参与者于1993 - 1995年提供血液样本，并随访至2004年8月（前列腺癌发病率）或直至2013年2月28日（致命性前列腺癌）。通过定量PCR测量相对LTL，并计算为端粒重复拷贝数与单个基因（36B4）拷贝数的比值（T/S）。使用TaqMan OpenArray SNP基因分型平台进行基因分型。采用逻辑回归估计所有前列腺癌以及按Gleason分级、分期和致死性（转移或死亡）定义的亚型的比值比（OR）和95%置信区间（CI）。
结果
我们观察到LTL每增加一个标准差与所有前列腺癌（多变量调整OR 1.11，95% CI：1.01 - 1.22）、低级别前列腺癌（OR 1.13，95% CI：1.01 - 1.27）和局限性前列腺癌（OR 1.12，95% CI：1.01 - 1.24）呈正相关。其他亚型的相关性相似，但未达到统计学显著性。在亚组分析中，有家族病史的男性中，高级别和晚期前列腺癌（OR = 2.04，95% CI 1.00 - 4.17；P交互作用 = 0.06）或致死性疾病（OR = 2.37，95% CI 1.19 - 4.72；P交互作用 = 0.01）的相关性比无家族病史的男性更强。单核苷酸多态性（SNP）rs7726159的次要等位基因，此前已被证明与LTL呈正相关，在多重检验校正后与所有前列腺癌风险呈负相关（P = 0.0005）。
结论
在这项前瞻性研究中，较长的LTL与前列腺癌风险适度相关。有家族病史男性中侵袭性更强的癌症的更强相关性需要在更大规模研究中得到证实。
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