Morari Elaine Cristina, Lima Andre Bacellar Costa, Bufalo Natassia Elena, Leite Janaina Luisa, Granja Fabiana, Ward Laura Sterian
Laboratory of Cancer Molecular Genetics, Department of Medicine, Medical Sciences Faculty, State University of Campinas-UNICAMP, Tessalia Vieira de Camargo 126, 13084-970, Campinas, São Paulo, Brazil.
J Cancer Res Clin Oncol. 2006 Aug;132(8):521-8. doi: 10.1007/s00432-006-0099-3. Epub 2006 May 19.
A series of polymorphisms in germ-line DNA have been investigated in an effort to delineate polygenic models of cancer susceptibility and prognosis. As low-penetrance susceptibility genes may combine additively or multiplicatively and contribute to cancer incidence and to the response to chemotherapy, we studied GSTT1, GSTM1, GSTO2, GSTP1 and codon 72 of p53 genotype profiles in ovarian cancer patients.
We compared 69 ovarian cancer patients with 222 control healthy women paired for ethnic and life-style characteristics. Outcome was evaluated in 29 stage III and IV patients submitted to a platinum-based chemotherapy followed-up for 6-29 months (17 +/- 9 months).
GSTT1, GSTM1, GSTO2 and GSTP1 genes presented a similar genotype distribution, but codon 72 of p53 gene wild-type variant was less frequent in ovarian cancer patients than in controls (chi(2); P = 0.0004).
We were unable to demonstrate any association between the GST genotypes studied and the risk of ovarian cancer but the inheritance of a heterozygous Arg/Pro genotype of p53 increased the risk of ovarian cancer more than 2.5 times (OR = 2.571; 95% CI = 1.453-4.550). There was no association of the studied genes to any clinical or pathological feature of the patients or to their response to chemotherapy.
为了描绘癌症易感性和预后的多基因模型，人们对种系DNA中的一系列多态性进行了研究。由于低外显率的易感基因可能以累加或相乘的方式组合，并对癌症发病率和化疗反应产生影响，我们研究了卵巢癌患者中GSTT1、GSTM1、GSTO2、GSTP1基因以及p53基因型谱的第72位密码子。
我们将69例卵巢癌患者与222例按种族和生活方式特征配对的健康对照女性进行了比较。对29例接受铂类化疗的III期和IV期患者进行了6至29个月（17±9个月）的随访，并对结果进行了评估。
GSTT1、GSTM1、GSTO2和GSTP1基因呈现出相似的基因型分布，但卵巢癌患者中p53基因野生型变体的第72位密码子频率低于对照组（χ²；P = 0.0004）。
我们未能证明所研究的GST基因型与卵巢癌风险之间存在任何关联，但p53基因杂合子Arg/Pro基因型的遗传使卵巢癌风险增加了2.5倍以上（OR = 2.571；95% CI = 1.453 - 4.550）。所研究的基因与患者的任何临床或病理特征或化疗反应均无关联。
