Association of p53 genetic polymorphism (Arg72Pro) with estrogen receptor positive breast cancer risk in Japanese women
Association of p53 genetic polymorphism (Arg72Pro) with estrogen receptor positive breast cancer risk in Japanese women
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DOI：
10.1016/j.canlet.2004.03.031
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发表时间：
2004-07-16
期刊：
影响因子：
9.7
通讯作者：
Noguchi, S
中科院分区：
文献类型：
--
作者：
Noma, C;Miyoshi, Y;Noguchi, S
由于p53基因失活与乳腺癌的发病机制有关，因此认为p53基因第72位密码子多态性（p53（Arg 72 Pro））影响p53的功能可能对乳腺癌的发病风险有影响。因此，在本研究中，我们研究了p53（Arg 72 Pro）多态性与乳腺癌风险的关联。对191例乳腺癌患者和218例健康女性对照进行了病例对照研究。p53（Arg 72 Pro）多态性与乳腺癌的风险进行了研究，调整后的流行病学危险因素。并探讨了p53（Arg 72 Pro）基因多态性与乳腺癌临床病理特征的关系。此外，根据p53（Arg 72 Pro）多态性的基因型，比较体细胞p53突变的频率。与p53（72 Arg/Arg）纯合子相比，p53（72 Pro/Pro）纯合子雌激素受体（ER）阳性乳腺癌的危险性显著增加（校正比值比（OR）= 2.04，P = 0.04），而p53（72 Pro/Pro）纯合子与ER阴性乳腺癌的危险性之间未发现这种关联。根据绝经状态进行的亚组分析显示，p53（72 Pro/Pro）纯合子与绝经后妇女ER阳性乳腺癌的风险显著相关（调整OR = 3.42，P = 0.01），但在绝经前妇女中不相关。p53（72 Pro/Pro）基因型乳腺癌ER阳性率（82.8%）明显高于p53（72 Arg/Arg）基因型乳腺癌（54.5%）（P < 0.01）。p53基因突变分析显示，p53（72 Pro/pro）纯合子的突变频率（3.5%）低于p53（72 Arg/Arg）纯合子（10.5%）。提示p53（Arg 72 Pro）基因多态性与ER阳性乳腺癌的发病风险有关，尤其是绝经后妇女。p53（72 Arg/Arg）纯合子中p53基因突变频率高于p53（72 Pro/Pro）纯合子，这与p53（72 Pro/Pro）功能受损，p53（72 Pro/Pro）纯合子中p53基因需要进一步改变的程度低于p53（72 Arg/Arg）纯合子的论点相一致。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Since it is well established that inactivation of p53 is involved in pathogenesis of breast cancer, it seems to be reasonable to assume that p53 genetic polymorphism at codon 72 (p53(Arg72Pro)) which affects the function of p53 might have an influence on breast cancer risk. Thus, in the present study, we have studied the association of p53(Arg72Pro) polymorphism with breast cancer risk. A case-control study was conducted with 191 breast cancer patients and 218 healthy female controls. p53(Arg72Pro) polymorphism was examined in their association with breast cancer risk after adjustment for the epidemiological risk factors. Relationship between p53(Arg72Pro) polymorphism and clinicopathological characteristics of breast cancers was also studied. In addition, frequency of somatic p53 mutation was compared according to the genotype of p53(Arg72Pro) polymorphism. p53(72Pro/Pro) homozygotes showed a significant increase in the risk of estrogen receptor (ER) positive breast cancer (adjusted odds ratio (OR) = 2.04, P = 0.04) as compared with p53(72Arg/Arg) homozygotes, whereas such an association was not found between p53(72Pro/Pro) homozygotes and ER negative breast cancer risk. Subset analysis according to menopausal status showed that p53(72Pro/Pro) homozygotes were significantly associated with ER positive breast cancer risk in postmenopausal women (adjusted OR = 3.42, P = 0.01) but not in premenopausal women. Frequency of ER positive tumors was significantly (p < 0.01) higher in breast cancer patients with p53(72Pro/Pro) genotype (82.8%) than those with p53(72Arg/Arg) genotype (54.5%). Mutational analysis of p53 in tumors showed that p53(72Pro/pro) homozygotes had a lower frequency of p53 mutation (3.5%) than p53(72Arg/Arg) homozygotes (10.5%). It is suggested that p53(Arg72Pro) polymorphism is associated with ER positive breast cancer risk, especially, in postmenopausal women. The higher frequency of p53 somatic mutation in p53(72Arg/Arg) homozygotes than p53(72Pro/Pro) homozygotes is consistent with the thesis that the function of p53(72Pro/Pro) is impaired so that a further alteration of p53 gene is less required in p53(72Pro/Pro) homozygotes than p53(72Arg/Arg) homozygotes. (C) 2004 Elsevier Ireland Ltd. All rights reserved.