Characterizing associations and SNP-environment interactions for GWAS-identified prostate cancer risk markers--results from BPC3.
Characterizing associations and SNP-environment interactions for GWAS-identified prostate cancer risk markers--results from BPC3.
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DOI：
10.1371/journal.pone.0017142
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发表时间：
2011-02-24
期刊：
影响因子：
3.7
通讯作者：
Kraft P
中科院分区：
文献类型：
--
作者：
Lindstrom S;Schumacher F;Siddiq A;Travis RC;Campa D;Berndt SI;Diver WR;Severi G;Allen N;Andriole G;Bueno-de-Mesquita B;Chanock SJ;Crawford D;Gaziano JM;Giles GG;Giovannucci E;Guo C;Haiman CA;Hayes RB;Halkjaer J;Hunter DJ;Johansson M;Kaaks R;Kolonel LN;Navarro C;Riboli E;Sacerdote C;Stampfer M;Stram DO;Thun MJ;Trichopoulos D;Virtamo J;Weinstein SJ;Yeager M;Henderson B;Ma J;Le Marchand L;Albanes D;Kraft P
全基因组关联研究（GWAS）已经确定了与前列腺癌风险相关的多个单核苷酸多态性（SNP）。然而，这些关联是否可以一致地复制，是否随疾病侵袭性（肿瘤分期和分级）而变化和/或与非遗传潜在风险因素或其他SNP相互作用尚不清楚。因此，我们对来自NCI乳腺癌和前列腺癌队列联盟（BPC 3）的10，501例前列腺癌病例和10，831例对照的几种前列腺癌GWAS鉴定的区域的39个SNP进行了基因分型。我们复制了39个SNP中的36个（P值范围为0.01至10 - 28）。与PSA水平相关的两个位于KLK 3附近的SNPs与Gleason分级呈差异性相关（rs 2735839，P = 0.0001和rs 266849，P = 0.0004;仅病例检验），其中与降低的PSA水平相关的等位基因与低级别（如Gleason等级<8所定义的）肿瘤负相关，但与高级别肿瘤正相关。没有其他SNP显示出根据疾病阶段或等级的差异关联。我们没有观察到SNP对诊断时年龄、前列腺癌家族史、糖尿病、BMI、身高、吸烟或饮酒的影响。此外，我们没有发现成对SNP-SNP相互作用的证据。虽然这些SNP代表了前列腺癌的新的独立风险因素，但我们几乎没有看到其他SNP或环境因素影响的证据。
Genome-wide association studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. However, whether these associations can be consistently replicated, vary with disease aggressiveness (tumor stage and grade) and/or interact with non-genetic potential risk factors or other SNPs is unknown. We therefore genotyped 39 SNPs from regions identified by several prostate cancer GWAS in 10,501 prostate cancer cases and 10,831 controls from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We replicated 36 out of 39 SNPs (P-values ranging from 0.01 to 10−28). Two SNPs located near KLK3 associated with PSA levels showed differential association with Gleason grade (rs2735839, P = 0.0001 and rs266849, P = 0.0004; case-only test), where the alleles associated with decreasing PSA levels were inversely associated with low-grade (as defined by Gleason grade <8) tumors but positively associated with high-grade tumors. No other SNP showed differential associations according to disease stage or grade. We observed no effect modification by SNP for association with age at diagnosis, family history of prostate cancer, diabetes, BMI, height, smoking or alcohol intake. Moreover, we found no evidence of pair-wise SNP-SNP interactions. While these SNPs represent new independent risk factors for prostate cancer, we saw little evidence for effect modification by other SNPs or by the environmental factors examined.
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影响因子：
168.9
作者：
Grönberg, H
通讯作者：
Grönberg, H
影响因子：
11.2
作者：
Hsu FC;Sun J;Wiklund F;Isaacs SD;Wiley KE;Purcell LD;Gao Z;Stattin P;Zhu Y;Kim ST;Zhang Z;Liu W;Chang BL;Walsh PC;Duggan D;Carpten JD;Isaacs WB;Grönberg H;Xu J;Zheng SL
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Zheng SL
影响因子：
30.8
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Gudmundsson, Julius;Sulem, Patrick;Gudbjartsson, Daniel F.;Blondal, Thorarinn;Gylfason, Arnaldur;Agnarsson, Bjarni A.;Benediktsdottir, Kristrun R.;Magnusdottir, Droplaug N.;Orlygsdottir, Gudbjorg;Jakobsdottir, Margret;Stacey, Simon N.;Sigurdsson, Asgeir;Wahlfors, Tiina;Tammela, Teuvo;Breyer, Joan P.;McReynolds, Kate M.;Bradley, Kevin M.;Saez, Berta;Godino, Javier;Navarrete, Sebastian;Fuertes, Fernando;Murillo, Laura;Polo, Eduardo;Aben, Katja K.;van Oort, Inge M.;Suarez, Brian K.;Helfand, Brian T.;Kan, Donghui;Zanon, Carlo;Frigge, Michael L.;Kristjansson, Kristleifur;Gulcher, Jeffrey R.;Einarsson, Gudmundur V.;Jonsson, Eirikur;Catalona, William J.;Mayordomo, Jose I.;Kiemeney, Lambertus A.;Smith, Jeffrey R.;Schleutker, Johanna;Barkardottir, Rosa B.;Kong, Augustine;Thorsteinsdottir, Unnur;Rafnar, Thorunn;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
30.8
作者：
Eeles, Rosalind A.;Kote-Jarai, Zsofia;Easton, Douglas F.
通讯作者：
Easton, Douglas F.
影响因子：
8.8
作者：
Bagnardi V;Blangiardo M;La Vecchia C;Corrao G
通讯作者：
Corrao G