Association between KRAS gene polymorphisms and genetic susceptibility to breast cancer in a Chinese population

Abstract

Objective The KRAS gene has a pathophysiological role in the development of many cancers. This study aims to investigate the relationship between KRAS polymorphisms and genetic susceptibility to breast cancer. Method The rs712, rs12587 and rs9266 gene loci in the KRAS gene of 421 subjects (141 breast cancer patients, 141 benign breast tumours and 139 healthy controls) were analysed by the polymerase chain reaction and SNaPshot sequencing. Transcriptomic information on KRAS and corresponding clinical information was downloaded from the TCGA and GTEx databases. Differences in KRAS expression between breast cancer tissues and control tissues were analysed. Results We found no significant association between KRAS rs712 and rs12587 locus gene polymorphisms and an increased risk of developing benign breast tumours and breast cancer (p > 0.05). The KRAS rs9266 locus mutation heterozygous model CT and dominant model CT + TT were significantly associated with an increased risk of breast cancer (both p < 0.05). In addition, the TAT haplotype was expressed at an increased frequency, and the GAC haplotype was expressed at a reduced frequency in breast cancer compared with controls (both p < 0.05). We found that KRAS was over expressed in breast cancer tumour tissues compared with the control tissues (p < 0.0001). Conclusion The KRAS rs9266 gene polymorphism and the TAT haplotype may be associated with an increased risk of breast cancer in Chinese women. The GAC haplotype may be a protective factor against breast cancer.

The importance of protein domain mutations in cancer therapy

“…protein domains have been predicted as frequently mutated domains and reported in the DCMP database. Protein Domain Target Function Reference BCL-2* Anti-apoptotic protein Apoptosis [ 191 ] CDK4/6 Cyclin-dependent kinases Cell cycle regulation [ 192 ] EGFR Epidermal growth factor receptor Cell proliferation, angiogenesis [ 193 ] FLT3* FMS-like tyrosine kinase 3 Cell survival, proliferation [ 194 ] HER2 Human epidermal growth factor receptor 2 Cell proliferation, survival [ 195 ] IDH1 Isocitrate dehydrogenase 1 Metabolic reprogramming [ 196 ] JAK2 Janus kinase 2 Cell proliferation, differentiation [ 197 ] KRAS Kirsten rat sarcoma viral oncogene homolog Cell proliferation, survival [ 198 ] mTOR Mammalian target of rapamycin Cell growth, metabolism [ 199 ] NTRK Neurotrophic tyrosine receptor kinase Cell survival, differentiation [ 200 ] PD-L1 Programmed death-ligand 1 …”

Association of the rs8720 and rs12587 KRAS Gene Variants with Colorectal Cancer in a Mexican Population and Their Analysis In Silico

“…Therefore, the variants analyzed in this study are present in mature mRNA and may play an important role in gene expression regulation via interactions with miRNAs [10]. Several studies have shown the association between SNVs present in the 3 UTR region of the KRAS gene and various types of cancer, including breast cancer, Wilms tumors, colorectal cancer, and glioma, among others [11][12][13][14][15][16][17]. According to the NIH SNP database, SNV rs12587 is located at chr12:25205894 (GRCh38.p14) and represents T > G transversion, whereas rs8720 is located at chr12:25206009 (GRCh38.p13) and entails the transition T > C. On the one hand, SNV rs12587 has been associated with Wilms tumor [12] and glioma [18], but it has not been associated with CRC [13].…”

“…In this study, we experimentally and in silico analyzed two SNVs, rs12587 and rs8720, both located in the 3 UTR region of the KRAS gene, a crucial regulatory region for gene expression. Numerous studies indicate that the post-transcriptional regulation of KRAS is mediated in this region by various miRNAs, suggesting that these variants may potentially interfere with its regulation [9,12,14,15]. These variants have been studied and associated with different types of cancer in diverse populations but not in the Mexican population, where studies on the association between KRAS gene variants and colorectal cancer are limited.…”