Haplotype-based association studies of IGFBP1 and IGFBP3 with prostate and breast cancer risk:: The multiethnic cohort
Haplotype-based association studies of IGFBP1 and IGFBP3 with prostate and breast cancer risk:: The multiethnic cohort
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DOI：
10.1158/1055-9965.epi-06-0361
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发表时间：
2006-10-01
影响因子：
3.8
通讯作者：
Freedman, Matthew L.
中科院分区：
文献类型：
--
作者：
Cheng, Iona;Penney, Kathryn L.;Freedman, Matthew L.
集体证据表明，胰岛素样生长因子(IGF)系统在前列腺癌和乳腺癌风险中发挥作用。胰岛素样生长因子结合蛋白(IGFBP)是调节IGF-I在血液循环和组织中的生物利用度的主要调节分子。为了检验IGFBP1和IGFBP3基因的遗传差异是否会影响前列腺癌和乳腺癌的易感性，我们对非裔美国人、夏威夷原住民、日裔美国人、拉丁美洲人和白人进行了两项基于人群的大型关联研究。为了彻底评估这两个基因座之间的遗传变异，我们(A)对95例侵袭性前列腺癌和95例晚期乳腺癌患者的IGFBP1和IGFBP3外显子进行了测序，以确保我们已经确定了所有常见的错义变异，并(B)通过对5个种族/民族的349名对照受试者的36个跨越71kb的单核苷酸多态(SNP)进行基因分型(上游类似于20kb，下游类似于40kb)，确定了连锁不平衡模式和常见的单倍型。未发现新的错义SNPs。我们确定了三个强连锁不平衡区域，并选择了23个标签SNPs的子集，可以准确预测常见的IGFBP1和IGFBP3单倍型以及其余13个SNPs。我们在多种族队列中嵌套的两项大型病例对照研究中测试了IGFBP1和IGFBP3基因及其单倍型与前列腺癌和乳腺癌风险的相关性[前列腺癌病例/对照=2,320/2,290；乳腺癌病例/对照=1,615/1,962]。我们没有观察到IGFBP1和IGFBP3基因或单倍型与前列腺癌或乳腺癌的风险有很强的相关性。我们的结果表明，IGFBP1和IGFBP3基因中常见的遗传变异对前列腺癌和乳腺癌的易感性没有实质性影响。
Collective evidence suggests that the insulin-like growth factor (IGF) system plays a role in prostate and breast cancer risk. IGF-binding proteins (IGFBP) are the principal regulatory molecules that modulate IGF-I bioavailability in the circulation and tissues. To examine whether inherited differences in the IGFBP1 and IGFBP3 genes influence prostate and breast cancer susceptibility, we conducted two large population-based association studies of African Americans, Native Hawaiians, Japanese Americans, Latinos, and Whites. To thoroughly assess the genetic variation across the two loci, we (a) sequenced the IGFBP1 and IGFBP3 exons in 95 aggressive prostate and 95 advanced breast cancer cases to ensure that we had identified all common missense variants and (b) characterized the linkage disequilibrium patterns and common haplotypes by genotyping 36 single nucleotide polymorphisms (SNP) spanning 71 kb across the loci (similar to 20 kb upstream and similar to 40 kb downstream, respectively) in a panel of 349 control subjects of the five racial/ethnic groups. No new missense SNPs were found. We identified three regions of strong linkage disequilibrium and selected a subset of 23 tagging SNPs that could accurately predict both the common IGFBP1 and IGFBP3 haplotypes and the remaining 13 SNPs. We tested the association between IGFBP1 and IGFBP3 genotypes and haplotypes for their associations with prostate and breast cancer risk in two large case-control studies nested within the Multiethnic Cohort [prostate cases/controls = 2,320/2,290; breast cases (largely postmenopausal)/controls = 1,615/1,962]. We observed no strong associations between IGFBP1 and IGFBP3 genotypes or haplotypes with either prostate or breast cancer risk. Our results suggest that common genetic variation in the IGFBP1 and IGFBP3 genes do not substantially influence prostate and breast cancer susceptibility.