一项来自JAMA的最新研究披露,那些有着较高风险评分的妇女(这些评分是由携带某些类型的与乳腺癌有着最强关联的基因变异体所组成的)与罹患乳腺癌的风险增加有关联,而这些评分也对雌激素受体阳性疾病有着高度的预测准确性。
文章的作者写道:“来自基因组范围内相关性研究(GWAS)的发现加上对特殊候选多态性[基因变异]的分析使得人们辨识出了数种肯定或可能与罹患乳腺癌风险有关的基因变异体。另外还有日益增多的证据显示,某些遗传因子对乳腺癌的不同亚型具有不同的影响。”
>>>借着上海世博会的良好契机,"第一届肿瘤基础和转化医学国际研讨会"将于2010年10月12日在中国上海盛大开幕,这将为广大活跃在肿瘤基础和转化医学第一线的科研工作者提供一个互动交流的平台。
会议官方网站:www.cancerasia.org
Cancer Epidemiology Unit, University of Oxford, U.K.的Gillian K. Reeves, Ph.D.及其同僚开展了一项研究,旨在分析乳腺癌风险(总体及各个肿瘤亚型的风险)与14种个体的单核苷酸多态性(SNPs)以及一个多基因(与一种由几种基因在同一时间所控制的可遗传特征的关系)风险评分之间的关系。 该研究中包括了1万306名罹患乳腺癌的妇女(平均诊断年龄为58岁)和1万393名没有患乳腺癌的妇女,这些人在2005-2008年期间提供了基因定型的血样本。 研究人员对个体SNPs的每个等位基因的风险比(OR)以及到70岁时的累计乳腺癌发病率与某一多基因风险评分之间的关系进行了评估(基于与乳腺癌风险最具强烈关联的4、7、或10个SNPs)。
研究人员发现,乳腺癌风险比最大的SNPs是FGFR2-rs2981582 和 TNRC9-rs3803662,对这2种SNPs来说,其发生雌激素受体(ER)阳性的几率要比雌激素受体阴性的几率显着要高;这两种情况都存在于此项研究的数据以及其它发表数据的荟萃分析之中。 下一个具有最强关联性的SNP 是2q-rs13387042,其每个等位基因的发生双侧性乳腺癌的OR要比发生单侧性乳腺癌的OR显着要高,发生小叶状瘤的可能性要比发生导管性瘤的可能性显着要高。
文章的作者写道:“在这些数据中,当与乳腺癌总体风险具有最强关联的7个SNPs的效应用一种多基因风险评分进行综合的话,女性在70岁时的乳腺癌累计风险在最高五分之一的女性中要比在最低五分之一的女性中高2倍(8.8% vs. 4.4%)。 ”
研究人员得出结论:“某些公认的乳腺癌风险因子对乳腺癌发病率的影响要比所见到的在最高五分之一 vs.最低五分之一的女性多基因风险评分之间的差别具有类似甚或更大的影响。确实,我们对在70岁时乳腺癌的累计发病率的估计发现,在发达国家的多基因风险评分的最高五分之一的女性(8.8%)与有一位罹患乳腺癌的一等亲属的女性(9.1%)相似,而要比那些有2位罹患乳腺癌一等亲(15.4%)的女性显着要少。此外,在这里被调查的基因的影响与乳腺癌的其它风险因子之间没有发现存在着相互作用。因此,正如其他人所提出的,在这一阶段,根据多基因风险对女性进行进一步的划分对基于人群的乳腺癌筛检计划不是一种有用的工具,但它可能对了解疾病的机制有用。”(生物谷Bioon.com)
生物谷推荐原文出处:
JAMA. 2010;304(4):426-434. doi:10.1001/jama.2010.1042
Incidence of Breast Cancer and Its Subtypes in Relation to Individual and Multiple Low-Penetrance Genetic Susceptibility Loci
Gillian K. Reeves, PhD; Ruth C. Travis, DPhil; Jane Green, DPhil; Diana Bull; Sarah Tipper, MSc; Krys Baker; Valerie Beral, MD, FRS; Richard Peto, MSc, FRS; John Bell, DM, FRS; Diana Zelenika, PhD; Mark Lathrop, PhD; for the Million Women Study Collaborators
Context There is limited evidence on how the risk of breast cancer and its subtypes depend on low-penetrance susceptibility loci, individually or in combination.
Objective To analyze breast cancer risk, overall and by tumor subtype, in relation to 14 individual single-nucleotide polymorphisms (SNPs) previously linked to the disease, and in relation to a polygenic risk score.
Design, Setting, and Participants Study of 10 306 women with breast cancer (mean age at diagnosis, 58 years) and 10 393 women without breast cancer who in 2005-2008 provided blood samples for genotyping in a large prospective study of UK women; and meta-analysis of these results and of other published results.
Main Outcome Measures Estimated per-allele odds ratio (OR) for individual SNPs, and cumulative incidence of breast cancer to age 70 years in relation to a polygenic risk score based on the 4, 7, or 10 SNPs most strongly associated with risk.
Results Odds ratios for breast cancer were greatest for FGFR2-rs2981582 and TNRC9-rs3803662 and, for these 2 SNPs, were significantly greater for estrogen receptor (ER)–positive than for ER-negative disease, both in our data and in meta-analyses of all published data (pooled per-allele ORs [95% confidence intervals] for ER-positive vs ER-negative disease: 1.30 [1.26-1.33] vs 1.05 [1.01-1.10] for FGFR2; interaction P < .001; and 1.24 [1.21-1.28] vs 1.12 [1.07-1.17] for TNRC9; interaction P < .001). The next strongest association was for 2q-rs13387042, for which the per-allele OR was significantly greater for bilateral than unilateral disease (1.39 [1.21-1.60] vs 1.15 [1.11-1.20]; interaction P = .008) and for lobular than ductal tumors (1.35 [1.23-1.49] vs 1.10 [1.05-1.15]; interaction P < .001). The estimated cumulative incidence (95% confidence interval) of breast cancer to age 70 years among women in the top and bottom fifths of a polygenic risk score based on 7 SNPs was 8.8% (8.3%-9.4%) and 4.4% (4.2%-4.8%), respectively. For ER-positive disease the corresponding risks were 7.4% (6.9%-8.0%) and 3.4% (3.1%-3.8%), respectively; while for ER-negative disease they were 1.4% (1.2%-1.6%) and 1.0% (0.8%-1.2%). The findings did not differ materially according to the number of SNPs included in the polygenic risk model.
Conclusions The polygenic risk score was substantially more predictive of ER-positive than of ER-negative breast cancer, particularly for absolute risk.