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阿根廷东北部多民族人群中的线粒体DNA血统、人乳头瘤病毒感染与宫颈癌风险

Mitochondrial DNA ancestry, HPV infection and the risk of cervical cancer in a multiethnic population of northeastern Argentina.

作者信息

Badano Ines, Sanabria Daiana J, Totaro Maria E, Rubinstein Samara, Gili Juan A, Liotta Domingo J, Picconi Maria A, Campos Rodolfo H, Schurr Theodore G

机构信息

Laboratorio de Biología Molecular Aplicada, Facultad de Ciencias Exactas, Químicas y Naturales, Universidad Nacional de Misiones, Misiones, Argentina.

Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.

出版信息

PLoS One. 2018 Jan 12;13(1):e0190966. doi: 10.1371/journal.pone.0190966. eCollection 2018.

Abstract

BACKGROUND

Misiones Province in northeastern Argentina is considered to be a region with a high prevalence of HPV infection and a high mortality rate due to cervical cancer. The reasons for this epidemiological trend are not completely understood. To gain insight into this problem, we explored the relationship between mitochondrial DNA (mtDNA) ancestry, HPV infection, and development of cervical lesions/cancer in women from the city of Posadas in Misiones Province.

METHODS

Two hundred and sixty-one women, including 92 cases of patients diagnosed with cervical lesions and 169 controls, were analyzed. mtDNA ancestry was assessed through HVS1 sequencing, while the detection and typing of HPV infection was conducted through nested multiplex PCR analysis. Multivariate logistic regression was conducted with the resulting data to estimate the odds ratios (ORs) adjusted by socio-demographic variables.

RESULTS

The study participants showed 68.6% Amerindian, 26.1% European and 5.3% African mtDNA ancestry, respectively. Multiple regression analysis showed that women with African mtDNAs were three times more likely to develop a cervical lesion than those with Native American or European mtDNAs [OR of 3.8 (1.2-11.5) for ancestry and OR of 3.5 (1.0-12.0) for L haplogroups], although the associated p values were not significant when tested under more complex multivariate models. HPV infection and the development of cervical lesions/cancer were significant for all tested models, with the highest OR values for HPV16 [OR of 24.2 (9.3-62.7)] and HPV-58 [OR of 19.0 (2.4-147.7)].

CONCLUSION

HPV infection remains a central risk factor for cervical cancer in the Posadas population. The potential role of African mtDNA ancestry opens a new avenue for future medical association studies in multiethnic populations, and will require further confirmation in large-scale studies.

摘要

背景

阿根廷东北部的米西奥内斯省被认为是HPV感染率高且宫颈癌死亡率高的地区。这种流行病学趋势的原因尚未完全了解。为深入了解这一问题,我们探讨了米西奥内斯省波萨达斯市女性的线粒体DNA(mtDNA)谱系、HPV感染与宫颈病变/癌症发展之间的关系。

方法

对261名女性进行了分析,其中包括92例被诊断为宫颈病变的患者和169名对照。通过HVS1测序评估mtDNA谱系,同时通过巢式多重PCR分析进行HPV感染的检测和分型。对所得数据进行多变量逻辑回归,以估计经社会人口统计学变量调整后的优势比(OR)。

结果

研究参与者的mtDNA谱系分别显示为68.6%的美洲印第安人、26.1%的欧洲人和5.3%的非洲人。多元回归分析表明,具有非洲mtDNA的女性发生宫颈病变的可能性是具有美洲原住民或欧洲mtDNA的女性的三倍[谱系的OR为3.8(1.2 - 11.5),L单倍群的OR为3.5(1.0 - 12.0)],尽管在更复杂的多变量模型下进行测试时,相关p值不显著。HPV感染以及宫颈病变/癌症的发展在所有测试模型中均具有显著性,HPV16的OR值最高[OR为24.2(9.3 - 62.7)],HPV - 58的OR值为19.0(2.4 - 147.7)。

结论

HPV感染仍然是波萨达斯人群宫颈癌的主要危险因素。非洲mtDNA谱系的潜在作用为未来多民族人群的医学关联研究开辟了一条新途径,并且需要在大规模研究中进一步证实。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/5766133/763fcfd08b3f/pone.0190966.g001.jpg

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