Trkova Marie, Prochazkova Kamila, Krutilkova Vera, Sumerauer David, Sedlacek Zdenek
Department of Biology and Medical Genetics, Charles University 2nd Medical School and University Hospital Motol, Prague, Czech Republic.
Cancer. 2007 Aug 1;110(3):694-702. doi: 10.1002/cncr.22834.
A decrease in the age at cancer onset and increase in cancer incidence in successive generations in Li-Fraumeni syndrome (LFS) families with germline TP53 mutations have been previously described. In the current study a possible relation was analyzed between telomere length and cancer onset in TP53 mutation carriers.
Telomere length was measured using real-time quantitative polymerase chain reaction (PCR) in 20 carriers of germline TP53 mutations and in 83 unrelated healthy individuals. According to the age at blood sampling, patients and controls were divided into 2 age groups, children and adults. Telomere length was correlated to TP53 mutation status and telomere shortening in patients to the age at cancer onset. A t-test and linear regression were used to analyze the data.
Compared with healthy controls, telomere length was significantly shorter both in the child (P = .001) and adult (P = .034) germline T53 mutation carriers. Although a statistically significant correlation between telomere shortening and the age at cancer onset was not observed, there was a trend of shorter telomeres in mutation carriers affected in childhood compared with those affected later in life. Neither cancer therapy nor sex differences were likely to affect the results.
The findings suggest a possible link between the carriership of a germline TP53 mutation, telomere length, predisposition to early-onset cancer, and anticipation in LFS.
先前已有报道，在携带种系TP53突变的李-弗劳梅尼综合征（LFS）家族中，癌症发病年龄下降且连续几代人的癌症发病率上升。在本研究中，分析了TP53突变携带者的端粒长度与癌症发病之间的可能关系。
使用实时定量聚合酶链反应（PCR）测量了20名种系TP53突变携带者和83名无关健康个体的端粒长度。根据采血年龄，将患者和对照分为儿童和成人两个年龄组。将端粒长度与TP53突变状态相关联，并将患者的端粒缩短与癌症发病年龄相关联。使用t检验和线性回归分析数据。
与健康对照相比，儿童（P = .001）和成人（P = .034）种系T53突变携带者的端粒长度均显著缩短。虽然未观察到端粒缩短与癌症发病年龄之间存在统计学显著相关性，但与成年后受影响的突变携带者相比，儿童期受影响的突变携带者的端粒有缩短趋势。癌症治疗和性别差异均不太可能影响结果。
研究结果表明，种系TP53突变携带者、端粒长度、早发性癌症易感性以及LFS中的遗传早现之间可能存在联系。
