11q13 和 12p11 位置的胚系遗传变异可调节肾细胞癌的发病年龄。

Germline genetic variations at 11q13 and 12p11 locus modulate age at onset for renal cell carcinoma.

机构信息

Centre de Recherche pour les Pathologies Prostatiques (FA, GC-T, PB, MA, CG, VO, FT, ARA, MR, OC), Paris, France; Academic Department of Urology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (MR), Université Pierre et Marie Curie (Université Paris 06), Paris, France; ONCOTYPE-Uro (FA, GC-T, MA, CG, VO, MR, OC), Université Pierre et Marie Curie (Université Paris 06), Paris, France; ER 2 (FA, GC-T, MA, FT, KA, OC), Université Pierre et Marie Curie (Université Paris 06), Paris, France; Academic Department of Urology, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris Descartes, University Paris V (FA, AM), Paris, France; Academic Department of Urology, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Groupement Hospitalier Universitaire Est (CG, VO, OC), Paris, France; Centre Hospitalier Universitaire d'Angers, Academic Department of Urology (PB, ARA), Angers, France; Sensors Signal and Information Processing Department, Information Models and Learning Laboratory, CEA LIST Institute, Saclay, France.

出版信息

J Urol. 2014 Feb;191(2):487-92. doi: 10.1016/j.juro.2013.07.064. Epub 2013 Aug 1.

DOI:10.1016/j.juro.2013.07.064

PMID:23911636

Abstract

PURPOSE

Few risk factors have been identified for renal cell carcinoma. We performed a validation study in a population with a European background to identify the most significant variants previously identified in association with renal cell carcinoma risk.

MATERIALS AND METHODS

We performed a case-control validation study after recruiting 463 controls and 463 patients with a histologically confirmed diagnosis of clear cell renal cell carcinoma. For each patient and matched control we genotyped 8 single nucleotide polymorphisms selected from previous studies to evaluate the association between candidate single nucleotide polymorphisms and renal cell carcinoma susceptibility.

RESULTS

After adjusting for patient age, gender, smoking status and body mass index the AG + AA genotypes from rs7105934 (11q13) were associated with a decreased risk of renal cell carcinoma (OR 0.50, 95% CI 0.33-0.75, p = 0.001) and the AC + CC genotypes from rs1049380 (ITPR2) were associated with an increased risk (OR 1.66, 95% CI 1.28-2.16, p <0.001). Kidney cancer developed at an older age in patients carrying the dominant risk allele A for rs7105934 (mean age at diagnosis 73.1 vs 68.9 years, p = 0.002) and at a younger age in those carrying the dominant allele C for rs1049380 (mean 68.1 vs 70.8 years, p = 0.005).

CONCLUSIONS

In what is to our knowledge the first validation study of the main 8 single nucleotide polymorphism variants associated with renal cell carcinoma susceptibility we confirmed the association of 2 single nucleotide polymorphisms with the risk of renal cell carcinoma. Each variant influenced patient age at disease diagnosis.

摘要

目的

目前仅发现少数肾癌的危险因素。我们在欧洲人群中开展了一项验证性研究，以鉴定与肾癌风险相关的最显著变异。

材料与方法

我们招募了 463 名对照者和 463 名经组织学证实为透明细胞肾细胞癌患者，开展了病例对照验证性研究。我们对每个患者和匹配对照者的 8 个单核苷酸多态性进行了基因分型，这些单核苷酸多态性是从前瞻性研究中选择的，旨在评估候选单核苷酸多态性与肾细胞癌易感性之间的关系。

结果

在调整了患者年龄、性别、吸烟状态和体重指数后，rs7105934（11q13）的 AG+AA 基因型与肾癌风险降低相关（OR0.50，95%CI0.33-0.75，p=0.001），rs1049380（ITPR2）的 AC+CC 基因型与肾癌风险升高相关（OR1.66，95%CI1.28-2.16，p<0.001）。携带 rs7105934 风险等位基因 A 的患者的肾癌发病年龄更大（诊断时的平均年龄为 73.1 岁，vs 68.9 岁，p=0.002），而携带 rs1049380 风险等位基因 C 的患者的肾癌发病年龄更小（诊断时的平均年龄为 68.1 岁，vs 70.8 岁，p=0.005）。