Mismatch repair gene polymorphisms and survival in invasive ovarian cancer patients.
Mismatch repair gene polymorphisms and survival in invasive ovarian cancer patients.
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DOI：
10.1016/j.ejca.2008.07.010
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Song H
中科院分区：
文献类型：
--
作者：
Mann A;Hogdall E;Ramus SJ;DiCioccio RA;Hogdall C;Quaye L;McGuire V;Whittemore AS;Shah M;Greenberg D;Easton DF;Ponder BA;Kjaer SK;Gayther SA;Thompson DJ;Pharoah PD;Song H
遗传遗传因素可能有助于部分解释卵巢癌患者生存时间的变异性。特别令人感兴趣的是与DNA修复有关的基因，特别是那些涉及错配修复(MMR)的基因。本研究的目的是探讨MMR基因常见变异与浸润性卵巢癌总生存率之间的可能联系。我们在来自英国(UK)、丹麦和美国加利福尼亚州的三项病例对照研究中，研究了七个MMR基因(MLH1、MLH3、MSH2、MSH3、MSH6、PMS1和PMS2)中标记已知常见变异(微小等位基因频率MMS0.05)的44个变异与侵袭性卵巢癌患者生存的关系。对多达1495名女性的DNA进行了基因分型。按研究分层进行COX回归分析，检验各基因多态与生存的相关性。在PMS2中观察到rs2228006基因与卵巢癌存活率之间名义上的显著关联(P=0.04)。每种罕见等位基因风险比(HR)为0.84(0.71~0.99)，调整多个协变量后差异无统计学意义(P=0.47)。当分析限于浆液性卵巢癌时，两个SNPs显示出边际显著关联；MLH1中rs1799977的每罕见等位基因HR为1.3(1.05-1.6)(P=0.02)，MSH3中rs6151662的每罕见等位基因HR为1.4(1.03-1.9)(P=0.04)。在调整多个协变量后，两者都不显著。在被诊断为卵巢癌后，MMR通路中的常见变异不太可能对生存率有适度的影响。需要进行更大规模的研究，以排除影响较小的常见变异。
Inherited genetic factors may help partially explain variability of survival length amongst ovarian cancer patients. Of particular interest are genes involved in DNA repair, specifically those involved in mismatch repair (MMR). The aim of this study was to investigate the possible association between the common variants in MMR genes and invasive ovarian cancer overall survival. We examined associations between 44 variants that tag the known common variants (minor allele frequency ≥0.05) in seven MMR genes (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2) and survival of invasive ovarian cancer patients in three case–control studies from United Kingdom (UK), Denmark and California of United States of America (USA). DNA from up to 1495 women were genotyped. The genotypes of each polymorphism were tested for association with survival using Cox regression analysis stratified by study. A nominally significant association (P = 0.04) between genotype and ovarian cancer survival was observed for rs2228006 in PMS2. The per-rare allele hazard ratio (HR 95%CI) was 0.84 (0.71–0.99), however, it was not significant after adjusting for multiple covariants (P = 0.47). When the analyses were restricted to serous type ovarian cancer, two SNPs showed marginal significant associations; the per-rare allele HR was 1.3 (1.05–1.6) (P = 0.02) for rs1799977 in MLH1 and 1.4 (1.03–1.9) (P = 0.04) for rs6151662 in MSH3. Neither was significant after adjusting for multiple covariants. It is unlikely that common variants in the MMR pathways examined have moderate effects on survival after diagnosis with ovarian cancer. Much larger studies would be needed to exclude common variants with small effects.
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影响因子：
3.7
作者：
Galic, Vijaya;Willner, Julia;Swisher, Elizabeth M.
通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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254.7
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Parkin, DM;Bray, F;Pisani, P
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