Abstract
Long non-coding RNA (lncRNA) steroid receptor RNA activator (SRA) has been identified to activate steroid receptor transcriptional activity and participate in tumor pathogenesis. This case-control study evaluated the association between two haplotype tagging SNPs (htSNPs) (rs10463297, rs801460) of the whole SRA sequence and breast cancer risk. We found that rs10463297 TC genotype significantly increased BC risk compared with CC genotype in both the codominant (TC vs. TT: OR=1.43, 95 % CI=1.02–2.00) and recessive (TC+CC vs. TT: OR=1.39, 95 % CI=1.01–1.92) genetic models. Both TC, TC + CC genotypes of rs10463297 and GA, AA, GA+AA genotypes of rs801460 were significantly associated with estrogen receptor (ER) positivity status. rs10463297 TC (2.09 ± 0.41), CC (2.42 ± 0.51) and TC + CC (2.20 ± 0.47) genotypes were associated with higher blood plasma SRA mRNA levels compared with the TT genotype(1.45 ± 0.34). Gene–reproductive interaction analysis presented a best model consisted of four factors (rs10463297, age, post-menopausal, No. of pregnancy), which could increase the BC risk with 1.58-fold (OR=1.58, 95 % CI=1.23–2.03). These findings suggest that SRA genetic variants may contribute to BC risk and have apparent interaction with reproductive factors in BC progression.
Highlights
Breast cancer is the most frequently diagnosed malignant tumor and the first leading cause of cancer death among females [1, 2]
These ‘non-coding RNAs’ were previously believed to be transcriptional noise, but accumulating evidences suggest that they play important roles in cell proliferation, differentiation, apoptosis, metabolism and immune [7]
H19 is an estrogen-inducible gene and plays a key role in www.impactjournals.com/oncotarget cell survival, which may serve as a biomarker for breast cancer diagnosis and progression [14], and a significantly decreased risk of bladder cancer was found for H19 rs2839698 TC carriers [15]. rs11752942 AG+GG in the lincRNA-uc003opf.1 exon had a significantly reduced risk of esophageal squamous cell carcinoma (ESCC), the rs11752942G allele could markedly attenuate the level of lincRNA-uc003opf.1 and affect cell proliferation and tumor growth [16]
Summary
Breast cancer is the most frequently diagnosed malignant tumor and the first leading cause of cancer death among females [1, 2]. Up to 98% of the transcriptional output of the human genome could represent RNA that do not code for protein [6] These ‘non-coding RNAs’ (ncRNAs) were previously believed to be transcriptional noise, but accumulating evidences suggest that they play important roles in cell proliferation, differentiation, apoptosis, metabolism and immune [7]. Over the past few years, a wealth of studies have highlighted the importance of small ncRNAs, especially microRNAs (miRNAs), in the development of cancers, and their variants were associated with various cancer risks [9,10,11]. Li et al, founded that the C to T base change at rs12325489 could disrupts the binding site for miRNA-370, influencing lincRNA-ENST00000515084 transcriptional activity and affecting breast cancer cell proliferation and tumor growth [18]
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