No evidence of linkage for chromosome 1q42.2-43 in prostate cancer.
No evidence of linkage for chromosome 1q42.2-43 in prostate cancer.
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没有证据表明前列腺癌中染色体 1q42.2-43 存在连锁。
DOI：
10.1086/302457
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发表时间：
1999
影响因子：
9.8
通讯作者：
Hsieh,CL
中科院分区：
文献类型：
--
作者：
Whittemore,AS;Lin,IG;Oakley-Girvan,I;Gallagher,RP;Halpern,J;Kolonel,LN;Wu,AH;Hsieh,CL
在对47个患有前列腺癌的法国和德国家庭进行全基因组搜索的基础上，Berthon等人(1998)报告了与染色体区域1q42的关联。2-43(多点非参数Z得分3.1，标记D1S2785)。这一发现很有趣，因为尽管D1S2785距离1q24-25区域相当远--由Smith等人(1996)鉴定为包含假定的遗传性前列腺癌基因HPC1--但它距离标记D1S235只有14厘米，后者在Smith等人的扫描中也产生了高Z分数。为了证实Berthon等人的发现，我们评估了与1q42中的三个标记的连锁。97个无血缘关系的家系中的2-43个区域，包含三个或三个以上经医学证实的一级或二级亲属的前列腺癌诊断。在这些家庭中，有82个符合前列腺癌可能是遗传性的家庭的一个或多个拟议标准(即，一个核心家庭中有三个或更多受影响的个人，连续三代受影响的个人，和/或两个或更多年龄在55岁的受影响个人)。七个家庭是非裔美国人，四个是日裔美国人，三个是华裔美国人。这些家庭是从谢家华等人(1997年)描述的几个来源确定的。每个家庭的平均患病人数和基因分型人数为2.6人(范围2-5)，所有患者的平均确诊年龄为66.9岁(白人家庭为67.0岁，非裔美国人家庭为64.1岁，亚裔美国人家庭为69.2岁)。受基因分型影响的个人总数和确诊时的总平均年龄与Berthon等人(1998)报告的家系相似。共有382个样本进行了这三个标记的基因分型。基因分型是由马什菲尔德医学基金会的NHLBI(国家心肺和血液研究所)哺乳动物基因分型服务进行的(袁等人。1997)，通过使用ABI 377测序仪来读取用于PCR产物的荧光标记的引物。我们对基因不明确或缺失的个体进行了重新分型，并对每个个体的一个或多个亲属进行了重新分型，以确保实验室间的可比性。所有样本都是在不知道疾病状况的情况下进行分类的。参数LOD分数、非参数Z分数和单尾P值由软件GENEHUNTER(Krugarak等人)获得。1996年)。对于参数分析，我们假设疾病易感等位基因具有频率的常染色体显性遗传模式。003和由Carter等人(1992)在分离分析中估计的渗透率。对于多点分析，假设这三个标记的顺序如表1所示。我们使用软件Fastlink(Cottingham等人)估计了这三个标记在家族创始人中的等位基因频率。1993年；Schaffer等人。(1994年)。
On the basis of a genomewide search involving 47 French and German families with multiple cases of prostate cancer, Berthon et al.(1998) reported linkage to chromosomal region 1q42. 2-43 (multipoint nonparametric Z score of 3.1, at marker D1S2785). P. 001 This finding is interesting because, although D1S2785 is considerably distal to the region 1q24-25—identified by Smith et al.(1996) as containing the putative hereditary prostate cancer locus HPC1—it is only 14 cM away from the marker D1S235, which also produced an elevated Z score in the scan by Smith et al. In an attempt to confirm the finding by Berthon et al., we have evaluated linkage to three markers in the 1q42. 2-43 region in 97 unrelated families containing three or more medically verified diagnoses of prostate cancer in first-or second-degree relatives. Eighty-two of these families fulfilled one or more of the proposed criteria for families whose prostate cancer is likely to be hereditary (ie, three or more affected individuals within one nuclear family, affected individuals in three successive generations, and/or two or more individuals affected at age! 55 years). Seven families were African American, four were Japanese American, and three were Chinese American. The families were identified from several sources, described by Hsieh et al.(1997). The mean number, per family, of affected and genotyped individuals was 2.6 (range 2–5), and the mean age at diagnosis of all affected individuals was 66.9 years (67.0 years in white families, 64.1 years in African American families, 69.2 years in Asian American families). The overall number of genotyped affected individuals and the overall mean age at diagnosis are similar to those found for the families reported by Berthon et al.(1998). A total of 382 samples were genotyped for the three markers. Genotyping was performed by the NHLBI (National Heart, Lung, and Blood Institute) Mammalian Genotyping Service at the Marshfield Medical Foundation (Yuan et al. 1997), by use of an ABI 377 sequencer to read fluorescently labeled primers for PCR products. We retyped individuals with ambiguous or missing genotypes and also retyped one or more relatives of each such individual to insure interlaboratory comparability. All samples were typed without knowledge of disease status. Parametric LOD scores, nonparametric Z scores, and one-tailed P values were obtained with the software GENEHUNTER (Kruglyak et al. 1996). For the parametric analyses, we assumed an autosomal dominant mode of inheritance of a disease-susceptibility allele with frequency. 003 and with penetrances as estimated in the segregation analysis by Carter et al.(1992). For the multipoint analyses, the three markers were assumed to be in the order shown in table 1. We estimated allele frequencies for the three markers in family founders, using the software FASTLINK (Cottingham et al. 1993; Schaffer et al. 1994).