Joint effects of germ-line p53 mutation and sex on cancer risk in Li-Fraumeni syndrome
Joint effects of germ-line p53 mutation and sex on cancer risk in Li-Fraumeni syndrome
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DOI：
10.1158/0008-5472.can-05-4247
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发表时间：
2006-08-15
期刊：
影响因子：
11.2
通讯作者：
Strong, Louise C.
中科院分区：
文献类型：
--
作者：
Wu, Chih-Chieh;Shete, Sanjay;Strong, Louise C.
在大多数患有Li-Fraumeni综合征（LFS）的家族中已经鉴定出生殖细胞精细p53突变。对于生殖系p53突变携带者，在癌症发病年龄和肿瘤类型方面存在相当大的变异性，这表明额外的遗传效应影响临床严重程度和肿瘤谱。为了确定可能导致观察到的发病时间异质性的因素，我们使用分离分析来分析生殖系p53突变和风险修饰因子对癌症发病率的联合影响。我们研究了159名儿童软组织肉瘤的先证者，这些先证者在16岁之前被诊断为儿童软组织肉瘤，在诊断后存活> 3年，并在德克萨斯大学医学博士接受治疗。安德森癌症中心（休斯顿，德克萨斯州），1944年至1975年。这个独特的队列已经系统地随访了20年以上，并在先证者和大家庭成员中进行了生殖系p53突变检测。分析显示，生殖系p53突变和性别对癌症风险有显著影响：携带p53突变的男性患癌症的几率比没有突变的男性高151倍[95%置信区间（95%CI），60 - 380]，携带p53突变的女性患癌症的几率比没有突变的女性高1,075倍（95%CI，358 - 3，229）和7.1倍的几率患癌症比男性突变（95%CI，2.5 - 20.3）。这些发现为LFS家庭提供了定量的癌症风险评估。
Germ-fine p53 mutations have been identified in most families with Li-Fraumeni syndrome (LFS). For germ-line p53 mutation carriers, there is considerable variability with respect to age of cancer onset and tumor type, suggesting that additional genetic effects influence the clinical severity and tumor spectrum. To identify factors that might contribute to the observed heterogeneity in time to onset, we used segregation analysis to analyze the joint effects of germ-line p53 mutations and risk modifier(s) on cancer incidence. We studied 159 kindreds, ascertained through probands who had been diagnosed with childhood soft-tissue sarcoma before 16 years of age, survived > 3 years after diagnosis, and treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX) from 1944 to 1975. This unique cohort has been followed systematically for > 20 years and has had germ-line p53 mutation testing in probands and extended family members. The analyses revealed that germ-line p53 mutations and sex had significant effects on cancer risk: men with p53 mutations had 151-fold higher odds of developing cancer than did those without mutations [95% confidence interval (95% Cl), 60-380], and women with p53 mutations had 1,075-fold higher odds than did those without mutations (95% Cl, 358-3,229) and 7.1-fold higher odds of having cancer than did men with mutations (95% Cl, 2.5-20.3). These findings provide quantitative cancer risk assessments for LFS families.