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Is the HERV-K HML-2 Xq21.33, an endogenous retrovirus mutated by gene conversion of chromosome X in a subset of African populations, associated with human breast cancer?
Infectious Agents and Cancer ( IF 3.7 ) Pub Date : 2020-03-07 , DOI: 10.1186/s13027-020-00284-w
Mark H Kaplan 1 , Rafael Contreras-Galindo 2 , Evelyn Jiagge 3 , Sofia D Merajver 4 , Lisa Newman 5 , Galya Bigman 6 , Michael H Dosik 7 , Ganesh S Palapattu 8 , Javed Siddiqui 9, 10 , Arul M Chinnaiyan 9, 10 , Sally Adebamowo 6 , Clement Adebamowo 6, 9, 10
Affiliation  

The human endogenous retroviruses HERV-K HML-2 have been considered a possible cause of human breast cancer (BrC). A HERV-K HML-2 fully intact provirus Xq21.33 was recently identified in some West African people. We used PCR technology to search for the Xq21.33 provirus in DNA from Nigerian women with BrC and controls. to see if Xq21.33 plays any role in predisposing to BrC. This provirus was detected in 27 of 216 (12.5%) women with BrC and in 22 of 219 (10.0%) controls. These results were not statistically significant. The prevalence of provirus in premenopausal control women 44 years or younger [18/157 (11.46%)} vs women with BrC [12/117 (10.26%)] showed no statistical difference. The prevalence of virus in postmenopausal control women > 45 yrs. was 7.4% (4/54) vs 15.31% (15/98) in postmenopausal women with BrC. These changes were not statistically significant at <.05, but the actual p value of <.0.079, suggests that Xq21.33 might play some role in predisposing to BrC in postmenopausal women. Provirus was present in Ghanaian women (6/87), in 1/6 Pygmy populations and in African American men (4/45) and women (6/68), but not in any Caucasian women (0/109). Two BrC cell lines (HCC 70 and DT22) from African American women had Xq21.33. E nv regions of the virus which differed by 2–3 SNPs did not alter the protein sequence of the virus. SNP at 5730 and 8529 were seen in all persons with provirus, while 54% had an additional SNP at 7596.Two Nigerian women and 2 Ghanaian women had additional unusual SNPs. Homozygosity was seen in (5/27) BrC and (2/22) control women. The genetic variation and homozygosity patterns suggested that there was gene conversion of this X chromosome associated virus. The suggestive finding in this preliminary data of possible increased prevalence of Xq21.33 provirus in post-menopausal Nigerian women with BrC should be clarified by a more statistically powered study sample to see if postmenopausal African and/or African American women carriers of Xq21.33 might show increased risk of BrC. The implication of finding such a link would be the development of antiretroviral drugs that might aid in preventing BrC in Xq21.33+ women.

中文翻译:

HERV-K HML-2 Xq21.33 是一种内源性逆转录病毒,它是在非洲人群的一个子集中通过染色体 X 的基因转换而突变的,它与人类乳腺癌有关吗?

人类内源性逆转录病毒 HERV-K HML-2 被认为是人类乳腺癌 (BrC) 的可能原因。最近在一些西非人中发现了一种 HERV-K HML-2 完全完整的原病毒 Xq21.33。我们使用 PCR 技术从患有 BrC 和对照的尼日利亚女性的 DNA 中寻找 Xq21.33 前病毒。看看 Xq21.33 是否在诱发 BrC 中起任何作用。在 216 名 BrC 女性中的 27 名(12.5%)和 219 名对照者中的 22 名(10.0%)中检测到这种原病毒。这些结果没有统计学意义。前病毒在 44 岁或以下的绝经前对照女性 [18/157 (11.46%)} 与 BrC 女性 [12/117 (10.26%)] 中的流行没有统计学差异。绝经后对照妇女中病毒的流行率 > 45 岁。在患有 BrC 的绝经后女性中为 7.4% (4/54) 与 15.31% (15/98)。这些变化在 <.05 时没有统计学意义,但实际 p 值 <.0.079,表明 Xq21.33 可能在绝经后妇女易患 BrC 方面发挥一定作用。原病毒存在于加纳女性 (6/87)、1/6 侏儒族群以及非裔美国男性 (4/45) 和女性 (6/68) 中,但不存在于任何白种女性 (0/109)。来自非洲裔美国女性的两个 BrC 细胞系(HCC 70 和 DT22)具有 Xq21.33。有 2-3 个 SNP 不同的病毒 Env 区不会改变病毒的蛋白质序列。5730 和 8529 的 SNP 在所有前病毒患者中都可见,而 54% 的人在 7596 处有额外的 SNP。两名尼日利亚妇女和两名加纳妇女有额外的不寻常 SNP。在 (5/27) BrC 和 (2/22) 对照女性中观察到纯合子。遗传变异和纯合模式表明这种 X 染色体相关病毒存在基因转换。该初步数据中关于 Xq21.33 前病毒在患有 BrC 的绝经后尼日利亚女性中的流行率可能增加的暗示性发现应通过更具统计效力的研究样本来澄清,以查看绝经后非洲和/或非裔美国女性是否携带 Xq21.33可能显示 BrC 的风险增加。发现这种联系意味着开发可能有助于预防 Xq21.33+ 女性发生 BrC 的抗逆转录病毒药物。33 患有 BrC 的绝经后尼日利亚女性中的前病毒应通过更具统计效力的研究样本来澄清,以查看 Xq21.33 的绝经后非洲和/或非裔美国女性携带者是否可能会增加 BrC 的风险。发现这种联系意味着开发可能有助于预防 Xq21.33+ 女性发生 BrC 的抗逆转录病毒药物。33 患有 BrC 的绝经后尼日利亚女性中的前病毒应通过更具统计效力的研究样本来澄清,以查看 Xq21.33 的绝经后非洲和/或非裔美国女性携带者是否可能会增加 BrC 的风险。发现这种联系意味着开发可能有助于预防 Xq21.33+ 女性发生 BrC 的抗逆转录病毒药物。
更新日期:2020-03-07
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