A common p73 polymorphism is associated with a reduced incidence of oesophageal carcinoma.
A common p73 polymorphism is associated with a reduced incidence of oesophageal carcinoma.
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DOI：
10.1054/bjoc.2001.2066
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发表时间：
2001-11-16
影响因子：
8.8
通讯作者：
Kelleher D
中科院分区：
文献类型：
--
作者：
Ryan BM;McManus R;Daly JS;Carton E;Keeling PW;Reynolds JV;Kelleher D
食管腺癌的发病率正在上升；到目前为止，还没有发现易感基因。P73是一种新的p53同源基因，定位于染色体1p36，这是食道癌中常见的缺失区域。P73具有一定的P53样活性，但也可能在胃肠上皮炎性反应中发挥作用。非编码p73多态(表示为AT或GC)可能在功能上具有重要意义。我们调查了这种多态是否可能在食道癌的发病机制中起作用。这是一项病例对照、回溯性研究。对84例食道癌(鳞癌25例，腺癌59例)和152例正常对照人群进行了基因分型。提供信息的病例检查了肿瘤内的p73杂合性缺失。AT/AT纯合子在食道癌人群中的发生率(1/84=1.2%)明显低于对照组(15/152=9.9%)(P<；0.02)，对应的优势比为0.11(95%C.I.0.02-0.6，P<；0.02)，或风险降低9倍。此外，在癌症人群中，AT/AT纯合子的发生率明显低于哈代-温伯格假说下的预期(P=0.0099)。在所研究的AT/GC杂合子中，37.8%(14/37)的AT/GC杂合子存在p73基因的杂合性缺失，所有病例均存在AT等位基因缺失。我们的发现表明，p73AT/AT纯合子似乎对食道癌的发生具有保护作用。在临床上，这一观察结果可能有助于识别高危的巴雷特食道患者。http://www.bjcancer.com 2001年癌症研究活动
The incidence of oesophageal adenocarcinoma is rising; to date, no susceptibility genes have been identified. p73, a novel p53 homologue, maps to chromosome 1p36, a region commonly deleted in oesophageal cancers. p73 shares some p53-like activity, but in addition, may also play a role in gastrointestinal epithelial inflammatory responses. A non-coding p73 polymorphism (denoted AT or GC) may be functionally significant. We investigated whether this polymorphism might play a role in the aetiopathogenesis of oesophageal cancer. This was a case–control, retrospective study. 84 cases of oesophageal cancer (25 squamous and 59 adenocarcinoma) and 152 normal population controls were genotyped for this polymorphism. Informative cases were examined for p73 LOH within the tumour. AT/AT homozygotes were significantly less prevalent in the oesophageal cancer population (1/84 = 1.2%) compared to controls (15/152 = 9.9%) (P < 0.02), corresponding to an odds ratio of 0.11 (95% C.I. 0.02–0.6, P < 0.02), or 9-fold reduced risk. Moreover, AT/AT homozygotes were significantly less frequent in the cancer population than would be expected under the Hardy–Weinberg hypothesis (P = 0.0099). LOH at the p73 locus was observed in 37.8% (14/37) of the AT/GC heterozygotes studied; in all cases there was loss of the AT allele. Our findings indicate that p73 AT/AT homozygotes appear to be protected against the development of oesophageal cancer. Clinically, this observation could have implications in aiding identification of high-risk Barrett's oesophagus patients.© 2001 Cancer Research Campaign http://www.bjcancer.com
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影响因子：
4.7
作者：
Chen, BS;Wang, MR;Wu, M
通讯作者：
Wu, M
影响因子：
8
作者：
Ichimiya, S;Nimura, Y;Nakagawara, A
通讯作者：
Nakagawara, A
影响因子：
8
作者：
Yokomizo, A;Mai, M;Liu, WG
通讯作者：
Liu, WG
影响因子：
30.8
作者：
Barrett, MT;Sanchez, CA;Reid, BJ
通讯作者：
Reid, BJ
具有不同转录活性的两个新的P73剪接变体伽马和三角洲。
影响因子：
15.3
作者：
De Laurenzi, V;Costanzo, A;Barcaroli, D;Terrinoni, A;Falco, M;Annicchiarico-Petruzzelli, M;Levrero, M;Melino, G
通讯作者：
Melino, G