Dataset Information

Genetic variants in lncRNA SRA and risk of breast cancer.

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.

SUBMITTER: Yan R

PROVIDER: S-EPMC5008375 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Genetic variants in lncRNA SRA and risk of breast cancer.

Yan Rui R Wang Kaijuan K Peng Rui R Wang Shuaibing S Cao Jingjing J Wang Peng P Song Chunhua C

Oncotarget 20160401 16

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. ...[more]

PMID: 26967566

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Project description:IntroductionBreast cancer in situ (BCIS) diagnoses, a precursor lesion for invasive breast cancer, comprise about 20 % of all breast cancers (BC) in countries with screening programs. Family history of BC is considered one of the strongest risk factors for BCIS.MethodsTo evaluate the association of BC susceptibility loci with BCIS risk, we genotyped 39 single nucleotide polymorphisms (SNPs), associated with risk of invasive BC, in 1317 BCIS cases, 10,645 invasive BC cases, and 14,006 healthy controls in the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3). Using unconditional logistic regression models adjusted for age and study, we estimated the association of SNPs with BCIS using two different comparison groups: healthy controls and invasive BC subjects to investigate whether BCIS and BC share a common genetic profile.ResultsWe found that five SNPs (CDKN2BAS-rs1011970, FGFR2-rs3750817, FGFR2-rs2981582, TNRC9-rs3803662, 5p12-rs10941679) were significantly associated with BCIS risk (P value adjusted for multiple comparisons <0.0016). Comparing invasive BC and BCIS, the largest difference was for CDKN2BAS-rs1011970, which showed a positive association with BCIS (OR = 1.24, 95 % CI: 1.11-1.38, P = 1.27 x 10(-4)) and no association with invasive BC (OR = 1.03, 95 % CI: 0.99-1.07, P = 0.06), with a P value for case-case comparison of 0.006. Subgroup analyses investigating associations with ductal carcinoma in situ (DCIS) found similar associations, albeit less significant (OR = 1.25, 95 % CI: 1.09-1.42, P = 1.07 x 10(-3)). Additional risk analyses showed significant associations with invasive disease at the 0.05 level for 28 of the alleles and the OR estimates were consistent with those reported by other studies.ConclusionsOur study adds to the knowledge that several of the known BC susceptibility loci are risk factors for both BCIS and invasive BC, with the possible exception of rs1011970, a putatively functional SNP situated in the CDKN2BAS gene that may be a specific BCIS susceptibility locus.

Project description:BackgroundGenome-wide association studies have identified several genomic regions that are associated with breast cancer risk, but these provide an explanation for only a small fraction of familial breast cancer aggregation. Genotype by environment interactions may contribute further to such explanation, and may help to refine the genomic regions of interest.MethodsWe examined genotypes for 4,988 SNPs, selected from recent genome-wide studies, and four randomized hormonal and dietary interventions among 2,166 women who developed invasive breast cancer during the intervention phase of the Women's Health Initiative (WHI) clinical trial (1993 to 2005), and one-to-one matched controls. These SNPs derive from 3,224 genomic regions having pairwise squared correlation (r2) between adjacent regions less than 0.2. Breast cancer and SNP associations were identified using a test statistic that combined evidence of overall association with evidence for SNPs by intervention interaction.ResultsThe combined 'main effect' and interaction test led to a focus on two genomic regions, the fibroblast growth factor receptor two (FGFR2) and the mitochondrial ribosomal protein S30 (MRPS30) regions. The ranking of SNPs by significance level, based on this combined test, was rather different from that based on the main effect alone, and drew attention to the vicinities of rs3750817 in FGFR2 and rs7705343 in MRPS30. Specifically, rs7705343 was included with several FGFR2 SNPs in a group of SNPs having an estimated false discovery rate < 0.05. In further analyses, there were suggestions (nominal P < 0.05) that hormonal and dietary intervention hazard ratios varied with the number of minor alleles of rs7705343.ConclusionsGenotype by environment interaction information may help to define genomic regions relevant to disease risk. Combined main effect and intervention interaction analyses raise novel hypotheses concerning the MRPS30 genomic region and the effects of hormonal and dietary exposures on postmenopausal breast cancer risk.

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Genetic variants in lncRNA SRA and risk of breast cancer.

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Genetic variants in lncRNA SRA and risk of breast cancer.

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