Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer.
Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer.
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DOI：
10.1001/jamaoncol.2017.0424
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发表时间：
2017-09-01
期刊：
影响因子：
28.4
通讯作者：
Dolinsky JS
中科院分区：
文献类型：
--
作者：
Couch FJ;Shimelis H;Hu C;Hart SN;Polley EC;Na J;Hallberg E;Moore R;Thomas A;Lilyquist J;Feng B;McFarland R;Pesaran T;Huether R;LaDuca H;Chao EC;Goldgar DE;Dolinsky JS
BRCA 1和BRCA 2中的生殖系致病性变异使乳腺癌的终生风险增加。然而，来自多基因遗传性癌症检测组的其他基因中的种系变异的相关性还没有很好地定义。确定与癌症易感基因生殖系变异相关的乳腺癌风险。研究人群为65057例乳腺癌患者，接受遗传性癌症多基因面板的癌症易感基因生殖系遗传检测。在乳腺癌患者和外显子组聚集联盟参考对照的病例对照分析中，估计了非BRCA 1和非BRCA 2易感基因中的致病性变异与乳腺癌风险之间的关联。这些女性在2012年3月15日至2016年6月30日期间接受了测试。非BRCA 1和非BRCA 2易感基因的致病性变异带来的乳腺癌风险纳入分析的65057名女性的平均（SD）诊断年龄为48.5（11.1）岁。在41611例连续检测的患有乳腺癌的白色女性中鉴定的21个面板基因中的致病性变体的频率估计为10.2%。排除BRCA 1、BRCA 2和综合征型乳腺癌基因后（CDH 1，PTEN和TP 53），观察到的16个基因中的5个致病性变异与乳腺癌的高或中度风险增加相关：ATM（OR，2.78; 95% CI，2.22-3.62），BARD 1（OR，2.16; 95%CI，1.31-3.63）、CHEK 2（OR，1.48; 95%CI，1.31-1.67）、PALB 2（OR，7.46; 95%CI，5.12-11.19）和RAD 51D（OR，3.07; 95%CI，1.21-7.88）。相反，BRIP 1和RAD 51 C卵巢癌风险基因的变异; MREHA，RAD 50和NBN MRN复合体基因; MLH 1和PMS 2错配修复基因;和NF 1与乳腺癌风险增加无关。这项研究建立了几个面板基因作为高风险和中等风险的乳腺癌基因，并提供了与这些基因中的致病性变异相关的乳腺癌风险的估计，这些基因在符合临床基因检测的个体中。
Germline pathogenic variants in BRCA1 and BRCA2 predispose to an increased lifetime risk of breast cancer. However, the relevance of germline variants in other genes from multigene hereditary cancer testing panels is not well defined. To determine the risks of breast cancer associated with germline variants in cancer predisposition genes. A study population of 65 057 patients with breast cancer receiving germline genetic testing of cancer predisposition genes with hereditary cancer multigene panels. Associations between pathogenic variants in non-BRCA1 and non-BRCA2 predisposition genes and breast cancer risk were estimated in a case-control analysis of patients with breast cancer and Exome Aggregation Consortium reference controls. The women underwent testing between March 15, 2012, and June 30, 2016. Breast cancer risk conferred by pathogenic variants in non-BRCA1 and non-BRCA2 predisposition genes. The mean (SD) age at diagnosis for the 65 057 women included in the analysis was 48.5 (11.1) years. The frequency of pathogenic variants in 21 panel genes identified in 41 611 consecutively tested white women with breast cancer was estimated at 10.2%. After exclusion of BRCA1, BRCA2, and syndromic breast cancer genes (CDH1, PTEN, and TP53), observed pathogenic variants in 5 of 16 genes were associated with high or moderately increased risks ofbreast cancer: ATM (OR, 2.78; 95% CI, 2.22-3.62), BARD1 (OR, 2.16; 95% CI, 1.31-3.63), CHEK2 (OR, 1.48; 95% CI, 1.31-1.67), PALB2 (OR, 7.46; 95% CI, 5.12-11.19), and RAD51D (OR, 3.07; 95% CI, 1.21-7.88). Conversely, variants in the BRIP1 and RAD51C ovarian cancer risk genes; the MREHA, RAD50, and NBN MRN complex genes; the MLH1 and PMS2 mismatch repair genes; and NF1 were not associated with increased risks of breast cancer. This study establishes several panel genes as high- and moderate-risk breast cancer genes and provides estimates of breast cancer risk associated with pathogenic variants in these genes among individuals qualifying for clinical genetic testing.
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影响因子：
28.4
作者：
Norquist BM;Harrell MI;Brady MF;Walsh T;Lee MK;Gulsuner S;Bernards SS;Casadei S;Yi Q;Burger RA;Chan JK;Davidson SA;Mannel RS;DiSilvestro PA;Lankes HA;Ramirez NC;King MC;Swisher EM;Birrer MJ
通讯作者：
Birrer MJ
DOI：
10.1186/bcr2919
发表时间：
2011-07-25
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Goldgar DE;Healey S;Dowty JG;Da Silva L;Chen X;Spurdle AB;Terry MB;Daly MJ;Buys SM;Southey MC;Andrulis I;John EM;BCFR;kConFab;Khanna KK;Hopper JL;Oefner PJ;Lakhani S;Chenevix-Trench G
通讯作者：
Chenevix-Trench G
DOI：
10.1038/gim.2014.40
发表时间：
2014-11
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1186/bcr3405
发表时间：
2013-03-19
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Win AK;Lindor NM;Jenkins MA
通讯作者：
Jenkins MA
DOI：
10.1073/pnas.1007983107
发表时间：
2010-07-13
影响因子：
11.1
作者：
Walsh, Tom;Lee, Ming K.;King, Mary-Claire
通讯作者：
King, Mary-Claire