Abstract
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. Env 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.
Highlights
The human endogenous retroviruses HERV-K HML-2 have been considered a possible cause of human breast cancer (BrC)
Most of these proviruses are in all humans, but some have arisen in limited areas of the world and in limited populations, occurring at different times in evolution with variable spread throughout the world
Great interest has been placed on seeing if any or some HERV-K HML-2 viruses can be linked to BrC, as these viruses are genetically distantly related to mammary tumor virus (MMTV)
Summary
The human endogenous retroviruses HERV-K HML-2 have been considered a possible cause of human breast cancer (BrC). The human endogenous retroviruses HERV-K HML-2 have been implicated as having some role in the pathogenesis of BrC as discussed below These retroviruses began to enter the evolving primate genome over 35,000,000 years ago (MYA) through infection, integrating in the genome of oocyte or spermatocyte cells. While the chromosomal proviruses entered the genome through either exogenous infection or endogenous reinfection, K111 and K222 probably entered the pericentromere and peripheral centromeric area first by infection Later they appear to have spread extensively and rapidly in modern man by homologous recombination throughout these areas of repetitive elements. When K113 was cloned into a modified pBluescript vector, while some viral proteins could be made, there was “inefficient particle formation, impaired synthesis of the Gag-Pro-Po precursor and a lack of envelope protein incorporation” felt to be “key factors in HER-K113 loss of replication capacity” [25]
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