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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. [ABSTRACT FROM AUTHOR]