HLA-G 14 bp Ins/Del (rs66554220) Variant Is Not Associated with Breast Cancer in Women from Western Mexico

Abstract

HLA-G is a physiology and pathologic immunomodulator detrimentally related to cancer. Its gene is heavily transcriptionally and post-transcriptionally regulated by variants located in regulator regions like 3'UTR, being the most studied Ins/Del of 14-bp (rs66554220), which is known to influence the effects of endogen cell factors; nevertheless, the reports are discrepant and controversial. Herein, the relationship of the 14-bp Ins/Del variant (rs66554220) with breast cancer (BC) and its clinical characteristics were analyzed in 182 women with non-familial BC and 221 disease-free women as a reference group. Both groups from western Mexico and sex-age-matched (sm-RG). The rs66554220 variant was amplified by SSP-PCR and the fragments were visualized in polyacrylamide gel electrophoresis. The variant rs66554220 was not associated with BC in our population. However, we suggest the Ins allele as a possible risk factor for developing BC at clinical stage IV (OR = 3.05, 95% CI = 1.16-7.96, p = 0.01); nevertheless, given the small stratified sample size (n = 11, statistical power = 41%), this is inconclusive. In conclusion, the 14-bp Ins/Del (rs66554220) variant of HLA-G is not associated with BC in the Mexican population, but might be related to advanced breast tumors. Further studies are required.

Keywords: 14-bp Ins/Del; HLA-G; Mexican population; breast cancer; clinical; rs66554220; stage IV; western Mexico.

Figure 1

Visualization of HLA-G 14-bp Ins/Del (rs66554220) variant genotypes via 6% polyacrylamide gel electrophoresis. Lane 1, 25 base-pair molecular-weight markers indicating 125 bp as the most intense band; lane 2, homozygous Ins/Ins genotype; lane 3, homozygous Del/Del genotype; and lane 4, heterozygous Del/Ins genotype.

Figure 2

Biological hypothesis about risk association of Ins allele of rs66554220 in HLA-G gene with clinical stage IV breast cancer. (a) As a background, HLA-G gene contains 8 exons; their last exon, the 3′UTR, contains the rs66554220 variant related to mRNA stability given the Ins/Del of 14-bp associated with decreased/augmented gene expression and soluble levels of the HLA-G protein, respectively. (b) According to this research, we proposed the biological hypothesis derived from the clinical suggestion of association between Ins allele and clinical stage IV in patients from western Mexico with breast cancer as a risk factor, because their biological function is related to epigenetic mechanisms, an immune-suppressive microenvironment and other microenvironmental factors that allow the immune surveillance and evasion of the system MHC-I non classical. Created with BioRender.com.