Campa Daniele, Rizzato Cosmeri, Stolzenberg-Solomon Rachael, Pacetti Paola, Vodicka Pavel, Cleary Sean P, Capurso Gabriele, Bueno-de-Mesquita H B As, Werner Jens, Gazouli Maria, Butterbach Katja, Ivanauskas Audrius, Giese Nathalia, Petersen Gloria M, Fogar Paola, Wang Zhaoming, Bassi Claudio, Ryska Miroslav, Theodoropoulos George E, Kooperberg Charles, Li Donghui, Greenhalf William, Pasquali Claudio, Hackert Thilo, Fuchs Charles S, Mohelnikova-Duchonova Beatrice, Sperti Cosimo, Funel Niccola, Dieffenbach Aida Karina, Wareham Nicholas J, Buring Julie, Holcátová Ivana, Costello Eithne, Zambon Carlo-Federico, Kupcinskas Juozas, Risch Harvey A, Kraft Peter, Bracci Paige M, Pezzilli Raffaele, Olson Sara H, Sesso Howard D, Hartge Patricia, Strobel Oliver, Małecka-Panas Ewa, Visvanathan Kala, Arslan Alan A, Pedrazzoli Sergio, Souček Pavel, Gioffreda Domenica, Key Timothy J, Talar-Wojnarowska Renata, Scarpa Aldo, Mambrini Andrea, Jacobs Eric J, Jamroziak Krzysztof, Klein Alison, Tavano Francesca, Bambi Franco, Landi Stefano, Austin Melissa A, Vodickova Ludmila, Brenner Hermann, Chanock Stephen J, Delle Fave Gianfranco, Piepoli Ada, Cantore Maurizio, Zheng Wei, Wolpin Brian M, Amundadottir Laufey T, Canzian Federico
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Int J Cancer. 2015 Nov 1;137(9):2175-83. doi: 10.1002/ijc.29590. Epub 2015 Jun 19.
A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 × 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D' = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 × 10(-5) ), rs4583925 (p = 4.0 × 10(-5) ) and rs2735948 (p = 5.0 × 10(-5) ). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants.
胰腺癌的少数常见易感基因座已被确定，其中一个以5号染色体p15.33上TERT-CLPTM1L基因区域的rs401681为标记。由于该区域的连锁不平衡程度较低，我们试图确定是否有其他单核苷酸多态性（SNP）与胰腺癌风险相关，且独立于rs401681。我们对端粒酶逆转录酶（TERT）和端粒酶RNA组分（TERC）基因的遗传变异性进行了深入分析，研究对象来自胰腺疾病研究（PANDoRA）和PanScan联盟的5550例胰腺癌患者及7585例对照。我们发现TERT中的一个变异与胰腺癌风险之间存在显著关联（rs2853677，比值比=0.85；95%置信区间=0.80-0.90，p=8.3×10⁻⁸）。对rs2853677针对rs401681进行调整的进一步分析表明，这两个SNP与胰腺癌风险独立相关，正如它们之间较低的连锁不平衡所表明的那样（r²=0.07，D'=0.28）。TERT中的另外三个SNP在多重检验校正后达到统计学显著性：rs2736100（p=3.0×10⁻⁵）、rs4583925（p=4.0×10⁻⁵）和rs2735948（p=5.0×10⁻⁵）。总之，我们证实TERT基因座与胰腺癌风险相关，可能是通过几个独立的变异。
