N. N. Olaya-Galán, S. P. Salas-Cárdenas, A. P. Corredor-Figueroa, G. Buehring, H. Shen, M. Patarroyo, Fernanda Gutierrez Ma
{"title":"4220:在患有和不患有乳腺癌的哥伦比亚妇女中检测到牛白血病病毒基因的证据:一种人畜共患感染","authors":"N. N. Olaya-Galán, S. P. Salas-Cárdenas, A. P. Corredor-Figueroa, G. Buehring, H. Shen, M. Patarroyo, Fernanda Gutierrez Ma","doi":"10.1158/1538-7445.AM2019-4220","DOIUrl":null,"url":null,"abstract":"Bovine leukemia virus (BLV), is an oncogenic virus that infects cattle worldwide and is the causative agent of leukemias, lymphomas and persistent lymphocytosis. BLV has also been found in humans and has recently been proposed as a risk factor for developing breast cancer in the USA and Australia. In Colombia, there is evidence of infection in women but no correlation with breast cancer. This study was aimed at comparing the presence of the virus in breast tissue from different sources: necropsies of women without tumor development (normal breast tissue), and surgeries of benign and malignant tumors, to better understand the role of BLV in Colombia. A cross-sectional study was designed in which 315 participants were included. Paired samples of breast tissue and blood were obtained from surgeries and necropsies in Bogota city. The presence of BLV was determined by nested PCR and in situPCR targeting different viral genes. For the nested PCR, DNA was extracted from fresh tissues and blood samples, and human GAPDH amplification was carried out to assess DNA quality for the PCRs. Afterwards, different BLV genes were detected by nested PCR. In situ PCR was directed to the tax region of the virus and was done to FFPE sections of the same samples. Positive samples were considered when at least one of the techniques was positive for the virus and were confirmed by Sanger sequencing. Correlation with other risk factors related with breast cancer (HER2, PR, ER and KI67) and the presence of the virus were determined. From the overall population, 40% of the samples were positive for BLV. In the breast cancer population, 37% of the samples were infected with the virus; similar distributions were found in the other groups (pre-malignant, 33%; benign tumors, 27%). Interestingly, almost 60% of the samples were infected in the no-tumor group. 22% of the samples were positive for both breast tissue and blood from the same patients. All the positive samples were confirmed to have BLV by Sanger sequencing of different gene regions of the virus. When correlating viral presence with other risk factors of breast cancer, it was found that most of the positive BLV samples were also positive for progesterone (79%) and estrogen (93%) receptors and were negative for the HER2 mutation. It could thus be possible that the hormonal profile could be linked with the presence of the virus. This study shows that irrespective of the breast pathology, BLV can be found in Colombian women both in breast tissue and blood. Sanger sequencing showed that the virus found in humans is similar to previously reported sequences obtained from cattle with high identity percentages. Even when the biology of the virus remains unknown in humans, it is a big concern to find the presence of an oncogenic virus coming from animals. Further studies are needed to understand the viral mechanisms related with cancer in humans. Citation Format: Nury N. Olaya-Galan, Sandra P. Salas-Cardenas, Adriana P. Corredor-Figueroa, Gertrude C. Buehring, HuaMin Shen, Manuel A. Patarroyo, Ma, Fernanda Gutierrez. Evidence of bovine leukemia virus genes detected in Colombian women with and without breast cancer: A zoonotic infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. 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In situ PCR was directed to the tax region of the virus and was done to FFPE sections of the same samples. Positive samples were considered when at least one of the techniques was positive for the virus and were confirmed by Sanger sequencing. Correlation with other risk factors related with breast cancer (HER2, PR, ER and KI67) and the presence of the virus were determined. From the overall population, 40% of the samples were positive for BLV. In the breast cancer population, 37% of the samples were infected with the virus; similar distributions were found in the other groups (pre-malignant, 33%; benign tumors, 27%). Interestingly, almost 60% of the samples were infected in the no-tumor group. 22% of the samples were positive for both breast tissue and blood from the same patients. All the positive samples were confirmed to have BLV by Sanger sequencing of different gene regions of the virus. When correlating viral presence with other risk factors of breast cancer, it was found that most of the positive BLV samples were also positive for progesterone (79%) and estrogen (93%) receptors and were negative for the HER2 mutation. It could thus be possible that the hormonal profile could be linked with the presence of the virus. This study shows that irrespective of the breast pathology, BLV can be found in Colombian women both in breast tissue and blood. Sanger sequencing showed that the virus found in humans is similar to previously reported sequences obtained from cattle with high identity percentages. Even when the biology of the virus remains unknown in humans, it is a big concern to find the presence of an oncogenic virus coming from animals. Further studies are needed to understand the viral mechanisms related with cancer in humans. Citation Format: Nury N. Olaya-Galan, Sandra P. Salas-Cardenas, Adriana P. Corredor-Figueroa, Gertrude C. Buehring, HuaMin Shen, Manuel A. 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引用次数: 0
摘要
牛白血病病毒(BLV)是一种全球感染牛的致癌病毒,是白血病、淋巴瘤和持续性淋巴细胞增多症的病原体。BLV也在人类中被发现,最近在美国和澳大利亚被认为是患乳腺癌的一个危险因素。在哥伦比亚,有证据表明妇女受到感染,但与乳腺癌没有关联。这项研究的目的是比较来自不同来源的乳腺组织中病毒的存在:没有肿瘤发展的妇女的尸检(正常乳腺组织),以及良性和恶性肿瘤的手术,以更好地了解BLV在哥伦比亚的作用。设计了一项横断面研究,其中包括315名参与者。从波哥大市的手术和尸检中获得了乳房组织和血液的成对样本。通过巢式PCR和定位不同病毒基因的原位PCR检测BLV的存在。对于巢式PCR,从新鲜组织和血液样本中提取DNA,并进行人GAPDH扩增以评估PCR的DNA质量。然后用巢式PCR检测不同BLV基因。将原位PCR定向到病毒的税区,并对相同样品的FFPE切片进行。当至少有一种技术对病毒呈阳性,并经桑格测序证实时,即视为阳性样本。确定与乳腺癌相关的其他危险因素(HER2、PR、ER和KI67)和病毒存在的相关性。从总体人群来看,40%的样本呈BLV阳性。在乳腺癌人群中,37%的样本感染了该病毒;其他组也有类似的分布(恶性前,33%;良性肿瘤,27%)。有趣的是,在无肿瘤组中,几乎60%的样本被感染。22%的样本对同一患者的乳腺组织和血液都呈阳性。所有阳性样本均经病毒不同基因区的Sanger测序证实为BLV。当将病毒的存在与乳腺癌的其他危险因素相关联时,发现大多数阳性BLV样本的孕激素受体(79%)和雌激素受体(93%)也呈阳性,HER2突变呈阴性。因此,荷尔蒙状况可能与病毒的存在有关。这项研究表明,无论乳房病理如何,在哥伦比亚妇女的乳房组织和血液中都可以发现BLV。Sanger测序显示,在人类中发现的病毒与先前报道的从牛中获得的具有高同一性百分比的序列相似。即使这种病毒在人类身上的生物学特性尚不清楚,发现来自动物的致癌病毒的存在也是一个很大的问题。需要进一步的研究来了解与人类癌症相关的病毒机制。引用格式:Nury N. Olaya-Galan, Sandra P. Salas-Cardenas, Adriana P. Corredor-Figueroa, Gertrude C. Buehring, HuaMin Shen, Manuel A. Patarroyo, Ma, Fernanda Gutierrez。在患有和不患有乳腺癌的哥伦比亚妇女中检测到牛白血病病毒基因的证据:一种人畜共患感染[摘要]。摘自:2019年美国癌症研究协会年会论文集;2019年3月29日至4月3日;亚特兰大,乔治亚州。费城(PA): AACR;癌症杂志,2019;79(13增刊):4220。
Abstract 4220: Evidence of bovine leukemia virus genes detected in Colombian women with and without breast cancer: A zoonotic infection
Bovine leukemia virus (BLV), is an oncogenic virus that infects cattle worldwide and is the causative agent of leukemias, lymphomas and persistent lymphocytosis. BLV has also been found in humans and has recently been proposed as a risk factor for developing breast cancer in the USA and Australia. In Colombia, there is evidence of infection in women but no correlation with breast cancer. This study was aimed at comparing the presence of the virus in breast tissue from different sources: necropsies of women without tumor development (normal breast tissue), and surgeries of benign and malignant tumors, to better understand the role of BLV in Colombia. A cross-sectional study was designed in which 315 participants were included. Paired samples of breast tissue and blood were obtained from surgeries and necropsies in Bogota city. The presence of BLV was determined by nested PCR and in situPCR targeting different viral genes. For the nested PCR, DNA was extracted from fresh tissues and blood samples, and human GAPDH amplification was carried out to assess DNA quality for the PCRs. Afterwards, different BLV genes were detected by nested PCR. In situ PCR was directed to the tax region of the virus and was done to FFPE sections of the same samples. Positive samples were considered when at least one of the techniques was positive for the virus and were confirmed by Sanger sequencing. Correlation with other risk factors related with breast cancer (HER2, PR, ER and KI67) and the presence of the virus were determined. From the overall population, 40% of the samples were positive for BLV. In the breast cancer population, 37% of the samples were infected with the virus; similar distributions were found in the other groups (pre-malignant, 33%; benign tumors, 27%). Interestingly, almost 60% of the samples were infected in the no-tumor group. 22% of the samples were positive for both breast tissue and blood from the same patients. All the positive samples were confirmed to have BLV by Sanger sequencing of different gene regions of the virus. When correlating viral presence with other risk factors of breast cancer, it was found that most of the positive BLV samples were also positive for progesterone (79%) and estrogen (93%) receptors and were negative for the HER2 mutation. It could thus be possible that the hormonal profile could be linked with the presence of the virus. This study shows that irrespective of the breast pathology, BLV can be found in Colombian women both in breast tissue and blood. Sanger sequencing showed that the virus found in humans is similar to previously reported sequences obtained from cattle with high identity percentages. Even when the biology of the virus remains unknown in humans, it is a big concern to find the presence of an oncogenic virus coming from animals. Further studies are needed to understand the viral mechanisms related with cancer in humans. Citation Format: Nury N. Olaya-Galan, Sandra P. Salas-Cardenas, Adriana P. Corredor-Figueroa, Gertrude C. Buehring, HuaMin Shen, Manuel A. Patarroyo, Ma, Fernanda Gutierrez. Evidence of bovine leukemia virus genes detected in Colombian women with and without breast cancer: A zoonotic infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4220.