A genome wide linkage search for breast cancer susceptibility genes.
A genome wide linkage search for breast cancer susceptibility genes.
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DOI：
10.1002/gcc.20330
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发表时间：
2006-07
影响因子：
3.7
通讯作者：
Stratton, Michael R
中科院分区：
文献类型：
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作者：
Smith, Paula;McGuffog, Lesley;Easton, Douglas F;Mann, Graham J;Pupo, Gulietta M;Newman, Beth;Chenevix-Trench, Georgia;Szabo, Csilla;Southey, Melissa;Renard, Helene;Odefrey, Fabrice;Lynch, Henry;Stoppa-Lyonnet, Dominique;Couch, Fergus;Hopper, John L;Giles, Graham G;McCredie, Margaret R E;Buys, Saundra;Andrulis, Irene;Senie, Ruby;Goldgar, David E;Oldenburg, Rogier;Kroeze-Jansema, Karin;Kraan, Jaennelle;Meijers-Heijboer, Hanne;Klijn, Jan G M;van Asperen, Christi;van Leeuwen, Inge;Vasen, Hans F A;Cornelisse, Cees J;Devilee, Peter;Baskcomb, Linda;Seal, Sheila;Barfoot, Rita;Mangion, Jon;Hall, Anita;Edkins, Sarah;Rapley, Elizabeth;Wooster, Richard;Chang-Claude, Jenny;Eccles, Diana;Evans, D Gareth;Futreal, P Andrew;Nathanson, Katherine L;Weber, Barbara L;Rahman, Nazneen;Stratton, Michael R
已知乳腺癌易感基因的突变占该疾病家族聚集性的一小部分。为了进一步寻找乳腺癌易感基因，我们对四个全基因组连锁筛选进行了联合分析，其中包括总共149个多例乳腺癌家族。所有家庭中至少有三例60岁以下的乳腺癌患者，其中至少有一人经过检测，发现没有携带BRCA1或BRCA2突变。使用参数连锁分析来评估连锁的证据，假设有显性和隐性遗传模式，并使用非参数方法。在优势模型下，在4号染色体上靠近标记D4S392的区域，在任何组合数据的分析中获得的最高LOD分数为1.80。在参数分析中确定了三个进一步的LOD分数超过1，在非参数分析中确定了两个。在年龄小于50岁且有4例或更多乳腺癌病例的家庭中，在2p染色体臂上的LOD评分最高为2.40。连锁峰的数目与偶然期望的数目没有差别。这些结果提示可能存在新的乳腺癌易感基因的区域。他们还指出，没有一个单一的基因可以解释大部分不是由BRCA1或BRCA2突变引起的乳腺癌家族聚集。
Mutations in known breast cancer susceptibility genes account for a minority of the familial aggregation of the disease. To search for further breast cancer susceptibility genes, we performed a combined analysis of four genome-wide linkage screens, which included a total of 149 multiple case breast cancer families. All families included at least three cases of breast cancer diagnosed below age 60 years, at least one of whom had been tested and found not to carry a BRCA1 or BRCA2 mutation. Evidence for linkage was assessed using parametric linkage analysis, assuming both a dominant and a recessive mode of inheritance, and using nonparametric methods. The highest LOD score obtained in any analysis of the combined data was 1.80 under the dominant model, in a region on chromosome 4 close to marker D4S392. Three further LOD scores over 1 were identified in the parametric analyses and two in the nonparametric analyses. A maximum LOD score of 2.40 was found on chromosome arm 2p in families with four or more cases of breast cancer diagnosed below age 50 years. The number of linkage peaks did not differ from the number expected by chance. These results suggest regions that may harbor novel breast cancer susceptibility genes. They also indicate that no single gene is likely to account for a large fraction of the familial aggregation of breast cancer that is not due to mutations in BRCA1 or BRCA2.