Genome-wide association study identifies multiple loci associated with bladder cancer risk
Genome-wide association study identifies multiple loci associated with bladder cancer risk
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DOI：
10.1093/hmg/ddt519
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发表时间：
2014-03-01
影响因子：
3.5
通讯作者：
Rothman, Nathaniel
中科院分区：
文献类型：
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作者：
Figueroa, Jonine D.;Ye, Yuanqing;Rothman, Nathaniel
候选基因和全基因组关联研究（GWAS）已经确定了11个与膀胱癌风险相关的独立易感基因座。为了发现其他风险变异，我们对2422例膀胱癌病例和5751例对照进行了新的GWAS，随后对两个独立发表的膀胱癌GWAS进行了荟萃分析，结果对6911例欧洲血统病例和11814例对照进行了综合分析。对801例患者和1307例对照者进行随访，对13个有希望的单核苷酸多态性进行TaqMan基因分型，P < 1 × 10（-5）。两个新的位点实现了全基因组的统计学显著性：3q26.2上的rs 10936599（P = 4.53 x 10（-9））和11p15.5上的rs 907611（P = 4.11 x 10（-8））。还鉴定了两个接近全基因组统计学显著性的显著位点：20p12.2上的rs6104690（P = 7.13 x 10（-7））和6p22.3上的rs 4510656（P = 6.98 x 10（-7））;这些需要进一步研究证实。总之，我们的研究已经确定了膀胱癌风险的新的易感等位基因，需要精细定位和实验室研究，这可以进一步了解膀胱癌发生的生物学基础。
Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 x 10(-5) was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 x 10(-9)) and rs907611 on 11p15.5 (P = 4.11 x 10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 x 10(-7)) and rs4510656 on 6p22.3 (P = 6.98 x 10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.