Stewart T H, Sage R D, Stewart A F, Cameron D W
University of Ottawa at Ottawa Hospital, Ontario, Canada.
Br J Cancer. 2000 Jan;82(2):446-51. doi: 10.1054/bjoc.1999.0941.
Incidence of human breast cancer (HBC) varies geographically, but to date no environmental factor has explained this variation. Previously, we reported a 44% reduction in the incidence of breast cancer in women fully immunosuppressed following organ transplantation (Stewart et al (1995) Lancet 346: 796-798). In mice infected with the mouse mammary tumour virus (MMTV), immunosuppression also reduces the incidence of mammary tumours. DNA with 95% identity to MMTV is detected in 40% of human breast tumours (Wang et al (1995) Cancer Res 55: 5173-5179). These findings led us to ask whether the incidence of HBC could be correlated with the natural ranges of different species of wild mice. We found that the highest incidence of HBC worldwide occurs in lands where Mus domesticus is the resident native or introduced species of house mouse. Given the similar responses of humans and mice to immunosuppression, the near identity between human and mouse MTV DNA sequences, and the close association between HBC incidence and mouse ranges, we propose that humans acquire MMTV from mice. This zoonotic theory for a mouse-viral cause of HBC allows testable predictions and has potential importance in prevention.
人类乳腺癌(HBC)的发病率在地理上存在差异,但迄今为止,尚无环境因素能够解释这种差异。此前,我们报道过器官移植后完全免疫抑制的女性乳腺癌发病率降低了44%(斯图尔特等人,《柳叶刀》,1995年,第346卷:796 - 798页)。在感染小鼠乳腺肿瘤病毒(MMTV)的小鼠中,免疫抑制也会降低乳腺肿瘤的发病率。在40%的人类乳腺肿瘤中检测到了与MMTV有95%同源性的DNA(王等人,《癌症研究》,1995年,第55卷:5173 - 5179页)。这些发现促使我们思考HBC的发病率是否与不同种类野生小鼠的自然分布范围相关。我们发现,全球HBC发病率最高的地区是小家鼠作为本地常住或引入的家鼠种类的地区。鉴于人类和小鼠对免疫抑制的反应相似、人类和小鼠MTV DNA序列近乎相同,以及HBC发病率与小鼠分布范围密切相关,我们提出人类从小鼠身上获得了MMTV。这种关于HBC由小鼠病毒引起的人畜共患病理论能够做出可检验的预测,并且在预防方面具有潜在的重要意义。