Genetic polymorphisms of HOTAIR gene are associated with the risk of breast cancer in a sample of southeast Iranian population

Abstract

There is an increasing body of evidence which highlights the critical functions of long non-coding RNAs in the carcinogenicity mechanism of a variety of cancers. It has been reported that HOX transcript antisense intergenic RNA, a member of long non-coding RNA family, increases breast cancer risk. To date, no data regarding the association between HOX transcript antisense intergenic RNA polymorphisms and the risk of breast cancer development has been reported in Iran. Here, we examine the possible association between HOX transcript antisense intergenic RNA gene polymorphisms and breast cancer in a sample of southeast Iranian female population. The HOX transcript antisense intergenic RNA rs920778, rs12826786, rs4759314, and 1899663 gene polymorphisms were genotyped in 220 cases and 231 controls by polymerase chain reaction-restriction fragment length polymorphism. Our findings indicated that rs920778 polymorphism has significant positive association with breast cancer; rs12826786 and rs1899663 polymorphisms demonstrated significant negative association with breast cancer; and the rs4759314 variant was not associated with breast cancer risk. Haplotype analysis revealed that TGAC, CTAT, and TTAT haplotypes significantly decreased the risk of breast cancer compared with rs920778T/rs1899663G/rs4759314A/rs12826786T haplotype. In conclusion, we investigated only four variants of HOX transcript antisense intergenic RNA gene, and the findings suggest that HOX transcript antisense intergenic RNA rs920778, rs12826786, and rs1899663 polymorphisms may be associated with breast cancer risk in a sample of southeast Iranian population. Further replication studies with other polymorphisms of HOX transcript antisense intergenic RNA gene involving a greater sample size and different ethnicities are necessary to verify our findings.

HOTAIR gene polymorphisms contribute to increased neuroblastoma susceptibility in Chinese children

“…39 The rs1899663 AA gene polymorphism was found to be associated with an increased risk of prostate cancer 37 and a decreased risk of breast cancer. 65 However, in a meta-analysis, no association was found between this SNP and breast cancer, gastric cancer, or esophageal squamous cell carcinoma. 39 To our knowledge, it is not clear whether the rs874945 or rs1899663 gene polymorphisms could affect the expression of HOTAIR.…”

“…The rs874945 TT gene polymorphism, which is located near rs12826786, was reported to be associated with increased risks of developing osteosarcoma in a meta‐analysis, and no association between this SNP and colorectal cancer, gastric cancer, or epithelial ovarian cancer (EOC) was found . The rs1899663 AA gene polymorphism was found to be associated with an increased risk of prostate cancer and a decreased risk of breast cancer . However, in a meta‐analysis, no association was found between this SNP and breast cancer, gastric cancer, or esophageal squamous cell carcinoma .…”

“…In the current study, we detected 3 HOTAIR genotypes (rs12826786 TT, rs874945 TT, and rs1899663 AA) that were found to be significantly related to an increased risk of neuroblastoma. In previous studies, rs12826786 TT, which is located in the HOTAIR promoter, was found to enhance the expression of HOTAIR and to be associated with increased risks of multiple cancers, including gastric cardia adenocarcinoma, prostate cancer, and breast cancer . The rs874945 TT gene polymorphism, which is located near rs12826786, was reported to be associated with increased risks of developing osteosarcoma in a meta‐analysis, and no association between this SNP and colorectal cancer, gastric cancer, or epithelial ovarian cancer (EOC) was found .…”

“…Several studies previously investigated the relationships between these 3 SNPs and cancer risks. The rs920778 A>G polymorphism, located in the intronic enhancer of HOTAIR , had a genotype‐specific effect on HOTAIR expression, and was associated with breast cancer and cervical cancer . The rs4759314 A>G polymorphism, located in TFBS, was associated with gastric cancer and EOC, and the rs7958904 G>C polymorphism, located in exon 6 of HOTAIR , was associated with colorectal cancer, EOC, osteosarcoma, and cervical cancer .…”

“…In previous studies, rs12826786 TT, which is located in the HOTAIR promoter, 36,64 was found to enhance the expression of HOTAIR 35,64 and to be associated with increased risks of multiple cancers, including gastric cardia adenocarcinoma, 35 prostate cancer, 37 and breast cancer. 36,65 The rs874945 TT gene polymorphism, which is located near rs12826786, was reported to be associated with increased risks of developing osteosarcoma in a meta-analysis, 39 and no association between this SNP and colorectal cancer, gastric cancer, or epithelial ovarian cancer (EOC) was found. 39 The rs1899663 AA gene polymorphism was found to be associated with an increased risk of prostate cancer 37 and a decreased risk of breast cancer.…”