一項(xiàng)來(lái)自JAMA的最新研究披露，那些有著較高風(fēng)險(xiǎn)評(píng)分的婦女（這些評(píng)分是由攜帶某些類型的與乳腺癌有著最強(qiáng)關(guān)聯(lián)的基因變異體所組成的）與罹患乳腺癌的風(fēng)險(xiǎn)增加有關(guān)聯(lián),，而這些評(píng)分也對(duì)雌激素受體陽(yáng)性疾病有著高度的預(yù)測(cè)準(zhǔn)確性,。
文章的作者寫道：“來(lái)自基因組范圍內(nèi)相關(guān)性研究（GWAS）的發(fā)現(xiàn)加上對(duì)特殊候選多態(tài)性[基因變異]的分析使得人們辨識(shí)出了數(shù)種肯定或可能與罹患乳腺癌風(fēng)險(xiǎn)有關(guān)的基因變異體。另外還有日益增多的證據(jù)顯示,，某些遺傳因子對(duì)乳腺癌的不同亞型具有不同的影響,。”
>>>借著上海世博會(huì)的良好契機(jī)，"第一屆腫瘤基礎(chǔ)和轉(zhuǎn)化醫(yī)學(xué)國(guó)際研討會(huì)"將于2010年10月12日在中國(guó)上海盛大開幕,，這將為廣大活躍在腫瘤基礎(chǔ)和轉(zhuǎn)化醫(yī)學(xué)第一線的科研工作者提供一個(gè)互動(dòng)交流的平臺(tái),。
會(huì)議官方網(wǎng)站：www.cancerasia.org
Cancer Epidemiology Unit, University of Oxford, U.K.的Gillian K. Reeves, Ph.D.及其同僚開展了一項(xiàng)研究，旨在分析乳腺癌風(fēng)險(xiǎn)（總體及各個(gè)腫瘤亞型的風(fēng)險(xiǎn)）與14種個(gè)體的單核苷酸多態(tài)性（SNPs）以及一個(gè)多基因（與一種由幾種基因在同一時(shí)間所控制的可遺傳特征的關(guān)系）風(fēng)險(xiǎn)評(píng)分之間的關(guān)系,。 該研究中包括了1萬(wàn)306名罹患乳腺癌的婦女（平均診斷年齡為58歲）和1萬(wàn)393名沒有患乳腺癌的婦女,，這些人在2005-2008年期間提供了基因定型的血樣本,。 研究人員對(duì)個(gè)體SNPs的每個(gè)等位基因的風(fēng)險(xiǎn)比（OR）以及到70歲時(shí)的累計(jì)乳腺癌發(fā)病率與某一多基因風(fēng)險(xiǎn)評(píng)分之間的關(guān)系進(jìn)行了評(píng)估（基于與乳腺癌風(fēng)險(xiǎn)最具強(qiáng)烈關(guān)聯(lián)的4、7,、或10個(gè)SNPs）,。
研究人員發(fā)現(xiàn)，乳腺癌風(fēng)險(xiǎn)比最大的SNPs是FGFR2-rs2981582 和 TNRC9-rs3803662,，對(duì)這2種SNPs來(lái)說(shuō),，其發(fā)生雌激素受體（ER）陽(yáng)性的幾率要比雌激素受體陰性的幾率顯著要高；這兩種情況都存在于此項(xiàng)研究的數(shù)據(jù)以及其它發(fā)表數(shù)據(jù)的薈萃分析之中,。 下一個(gè)具有最強(qiáng)關(guān)聯(lián)性的SNP 是2q-rs13387042,其每個(gè)等位基因的發(fā)生雙側(cè)性乳腺癌的OR要比發(fā)生單側(cè)性乳腺癌的OR顯著要高,，發(fā)生小葉狀瘤的可能性要比發(fā)生導(dǎo)管性瘤的可能性顯著要高。
文章的作者寫道：“在這些數(shù)據(jù)中,，當(dāng)與乳腺癌總體風(fēng)險(xiǎn)具有最強(qiáng)關(guān)聯(lián)的7個(gè)SNPs的效應(yīng)用一種多基因風(fēng)險(xiǎn)評(píng)分進(jìn)行綜合的話,，女性在70歲時(shí)的乳腺癌累計(jì)風(fēng)險(xiǎn)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%）。 ”
研究人員得出結(jié)論：“某些公認(rèn)的乳腺癌風(fēng)險(xiǎn)因子對(duì)乳腺癌發(fā)病率的影響要比所見到的在最高五分之一 vs.最低五分之一的女性多基因風(fēng)險(xiǎn)評(píng)分之間的差別具有類似甚或更大的影響,。確實(shí),，我們對(duì)在70歲時(shí)乳腺癌的累計(jì)發(fā)病率的估計(jì)發(fā)現(xiàn)，在發(fā)達(dá)國(guó)家的多基因風(fēng)險(xiǎn)評(píng)分的最高五分之一的女性（8.8%）與有一位罹患乳腺癌的一等親屬的女性（9.1%）相似,，而要比那些有2位罹患乳腺癌一等親（15.4%）的女性顯著要少,。此外，在這里被調(diào)查的基因的影響與乳腺癌的其它風(fēng)險(xiǎn)因子之間沒有發(fā)現(xiàn)存在著相互作用,。因此,，正如其他人所提出的，在這一階段,，根據(jù)多基因風(fēng)險(xiǎn)對(duì)女性進(jìn)行進(jìn)一步的劃分對(duì)基于人群的乳腺癌篩檢計(jì)劃不是一種有用的工具,，但它可能對(duì)了解疾病的機(jī)制有用。”(生物谷Bioon.com)
生物谷推薦原文出處：
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.
