两个单核苷酸多态位点与北方中国人前列腺癌的关联研究

摘要

背景与目的:近年来在不同人群的研究中,全基因组关联研究已经发现了许多与前列腺癌(prostate cancer,PCa)风险相关的单核苷酸多态性位点(single nucleotide polymorphisms,SNPs).本文探讨了两个SNPs,即rs17021918 (4q22)与rs 10090154 (8q24)和中国北方汉族人PCa的相关性.方法:采用病例对照的研究方法,本研究入选了124例PCa患者和111例健康对照者,采用聚合酶链反应-高分辨熔解曲线(PCRHRM)技术,并结合测序验证法,对rs17021918(4q22)与rs10090154 (8q24)进行基因型及等位基因频率的分析,并探讨其与确诊时的体重指数(body mass index,BMI)、Gleason评分、血清前列腺特异性抗原(prostate specific antigen,PSA)水平、肿瘤分期及年龄等临床特征之间的联系.结果:在风险等位基因、基因型及分层分析中,rs17021918虽然并未观察到有统计学意义的结果,但风险比(the odds ratio,OR)值多＜1,其中在BMI＞27.5 kg/m2(P=0.056； OR=0.292； 95％CI:0.078～1.095)和PSA浓度＜10.0 ng/mL组(P=0.068；OR=0.467； 95％CI:0.204～1.069),CC基因型携带者可能有较低的PCa发病风险；另外发现,rs10090154的T等位基因携带者与较低的肿瘤分期关联(P=0.012； OR=2.512； 95％CI:1.210～5.214),而在较高的肿瘤分期组,T等位基因携带者与非T等位基因携带者之间差异有统计学意义(P=0.039).结论:Rs17021918的CC基因型携带者可能与中国北方人PCa发病风险负关联；而rs10090154的T等位基因携带者可能与中国北方人PCa肿瘤分期正关联.%Background and purpose: Recent genome-wide association studies have identified multiple single nucleotide polymorphisms (SNPs) associated with prostate cancer (Pca) risk in different study populations. This study aims to determine whether two SNPs, rsl7021918 on chromosome 4q22 and rs 10090154 on chromosome 8q24, were associated with Pca risk in the northern Han Chinese population. Methods: We conducted a case- control study comprising of 124 prostate patients and 111 healthy controls. Using polymerase chain reaction-high resolution melting curve (PCR-HRM) combined with gene sequencing methods, genotyping was performed to test for the association between its risk allele and Pca. Their association with body mass index (BMI), tumor grade, prostate-specific antigen (PSA) level and age at diagnosis were also determined. Results: Although our study did not observe any statisticallysignificant results in rsl7021918, it showed odds ratio (OR) <1 in most analysis of risk allele, especially in two group, BMI >27.5 kg/m2 (P=0.056; OR=0.292; 95%C1: 0.078-1.095) and PSA level <10.0 ng/mL(/M)0.068; OR=0.467; 95%C/: 0.204-1.069), which suggests CC genotype might be inversely associated with Pca risk. In addition, T allele carrier of rs 10090154 was significantly associated with a lower tumor grade. But for the higher tumor grade, we only observed a statistical difference between T allele carrier and not T allele carrier (P=0.039). Conclusion: Our study showed that CC genotype carrier of rs 17021918 might be inversely associated with Pca risk. While T allele carrier of rs 10090154 was significantly associated with tumor grade.