Mir-485-5p binding site snp rs8752 in hpgd gene is associated with breast cancer risk s note data recovery
1Department of Epidemiology and Biostatistics, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P. Database backend R. Database b tree China
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We performed a two-stage case-control study including 2744 breast cancer cases and 3125 controls. Yale b database In Stage I, we genotyped 192 SNPs within microRNA binding sites identified from the “Patrocles” database using custom Illumina GoldenGate VeraCode assays on the Illumina BeadXpress platform. Ads b database In Stage II, genotyping was performed on SNPs potentially associated with breast cancer risk using the TaqMan platform in an independent replication set.
Breast cancer is the most common female malignancy worldwide, and its incidence has been increasing during the past several decades in both developing and developed countries . B tree database management system It is widely accepted that environmental and genetic factors contribute to the development of breast cancer.
Database concepts Despite environmental factors play an important role in breast cancer, the individual’s risk of breast cancer was determined by the genetic susceptibility. Database connection Numerous investigations have suggested that microRNAs are essential for various biological processes and diseases, including tumorigenesis , , , , , . Database cardinality MicroRNA inhibits gene translation by binding to the 3’ UTRs of target mRNAs. Database constraints In recent years, many studies have revealed that SNPs or mutations within microRNA binding sites may affect cancer susceptibility by disrupting miRNA-mRNA interaction and mRNA expression , , , . Database cleaner Several bioinformatic methods have been introduced to predict candidate SNPs located in microRNA target sites, including “Patrocles”, and “PolymiRTS” , , , , . Database collation Some case-control studies have been performed to investigate the association between SNPs in microRNA binding sites and breast cancer risk , , , , , . Database clustering Wang et al. Database cursor found that a miRNA binding site SNP in the 3′-UTR region of the IL23R gene may be associated with the risk of breast cancer and contribute to the early development of breast cancer in Chinese women . Database companies Teo et al. Database crud first reported the association between DNA repair gene PARP1 miRNA-binding site SNP rs8679 and breast cancer risk . C database library Zheng et al. C database tutorial reported that the presence of SNPs at the miR-124 binding site may be a marker for breast cancer risk and prognosis . Database developer Kontorovich et al. Database developer salary found that the heterozygotes carriers of SNP rs11169571 had an approximately 2 fold increased risk for developing breast cancer, whereas heterozygotes of the rs895819 SNP had an approximately 50% reduced risk for developing breast cancer . Database design tool Saetrom et al. Database diagram tool suggested that allele-specific regulation of BMPR1B by miR-125b explains the observed disease risk . Database disk image is malformed Brendle et al. Database design for mere mortals showed that the A allele of the ITGB4 SNP rs743554 was associated with the negative hormone receptor status and bad breast cancer-specific survival, especially in women with more aggressive tumors . Database data types However, most of them are candidate gene studies including only a few SNPs, which could not represent the whole situation of these SNPs in breast cancer etiology.
In this study, high-throughput SNP genotyping was used in a large case-control study including genome-wide microRNA binding site SNPs. Database denormalization The results may provide new insights into the cause of breast cancer, and new molecular markers for breast cancer diagnosis.
The Ethics Committee of Tianjin Medical University Cancer Institute and Hospital approved the study protocol, and all patients and controls gave written informed consent before participating in the study.
A total of 5869 individuals (2744 breast cancer cases and 3125 controls) were involved in this study. Database d b The cases were collected from Tianjin Medical University Cancer Hospital between January 1, 2006 and December 31, 2008 who were newly diagnosed and histologically confirmed breast cancer patients. P d database At the same time, controls were enrolled from the nearby community, who were genetically unrelated to the patients and were frequency matched to the patients by age (±3 years). Database engineer Our study comprised two stages, in stage I, we randomly selected 1349 patients and 1572 cancer-free female controls for SNP screening. Database entity In stage II, to validate the findings from stage I, the validation set of 1395 cases and 1553 controls were genotyped. Database engineer salary Participants were interviewed by trained investigator using a systematic questionnaire about their demographic characteristics, personal habits, family history, occupational exposure history, eating habits, physical exercise, and reproductive factors. Database error For the cases, clinical information on tumor features and disease severity, including morphology, tumor size, lymph node metastasis, organ metastasis, tumor stage, and status of estrogen receptor (ER) and progesterone receptor (PR) were also collected. Database engine tuning advisor Each participant provided 10 ml venous blood. Database erd The study was approved by the Institutional Review Board of Tianjin Medical University; informed consent was obtained from all patients.
The “Patrocles” online database ( http://www.patrocles.org/) was used to select genome-wide micro-RNA target SNPs. Database etl Among all the 5035 SNPs in microRNA binding site SNPs that the database provided, 1742 SNPs had been confirmed. Database er diagram SNPs that satisfy the following criteria were considered for inclusion: (1) SNPs were located in a microRNA-seed region binding site, and the seed region was defined according to the “7-mirs” criteria . Database entry (2) SNPs have reported population frequency data in Chinese (htpp:// www.ncbi.nlm.nih.gov/snp/), and SNPs with minor genotype frequency ≥0.05 were included. Database field In this way, a total of 192 microRNA target SNPs were included in our study, the detailed information for these SNPs can be seen in Table S1 in File S1.
A χ 2 test was used to evaluate the differences in the distributions of major demographic variables and environmental risk factors, as well as the genotypes of selected SNPs between the breast cancer cases and controls. Database foreign key The Hardy-Weinberg equilibrium was determined by a χ 2 goodness of fit test in controls. Database fundamentals Unconditional logistic regression was used to examine the association between the SNPs and breast cancer risk by estimating the odds ratios (ORs) and 95% confident intervals (CIs), with and without adjustments for age, smoking status, menopause status, oral contraception use, history of benign breast diseases, and family history of cancer. Database first entity framework All statistical tests were two-sided, and a P value of 0.05 was considered significant, correction for multiple comparisons was not performed. Database file We used the SAS software version 9.0 (SAS Institute) for all statistical analyses.
In this study, we performed a two-stage case-control study including 2744 cases and 3125 controls. Database functions Among the 192 SNPs genotyped, the SNP rs8752 (A allele) in HPGD gene was identified to be associated with an increased risk of breast cancer in both stages. Database for dummies This study provided a piece of evidence for a novel susceptibility variation for breast cancer on chromosome 4q34-35.
Our study covered three SNPs ( IGF1R rs2654981, NFAT5 rs7359387, NELF rs1059111) that were previously studied in the context of breast cancer risk. Database form The IGF1 receptor ( IGF1R) overexpression has been associated with a number of hematological neoplasias and solid tumors including breast cancer . Database field definition Han-Sung Kang found that seven of the 51 IGF1R SNPs were in LD (linkage disequilibrium) and in one haplotype block, and were likely to be associated with breast cancer risk . Database field types Sebastien Jauliac found that NFAT5 were expressed in invasive human ductal breast carcinomas and participate in promoting carcinoma invasion using cell lines derived from human breast and colon carcinomas . Database google NEFL has been shown to act as a tumor suppressor in the carcinogenesis of breast , . Database gui However, we found significant association between these three SNPs and breast cancer risk only in stage I. Database gif In stage II (the validation set),we did not find significant association.
The microRNA-related SNPs can generally be categorized into three groups, SNPs in microRNA sequences, SNPs in microRNA biogenesis pathway genes, and SNPs in microRNA target sites , , . Database generator Up to now, SNPs in microRNA sequences and microRNA biogenesis pathway genes had been systematically studied and important findings were reported from these studies , . Database graphic However, for the association between microRNA binding site SNPs and breast cancer risk, most previous studies were based on candidate gene strategy. Database graph Results from these studies were not enough to represent the role of such SNPs in the etiology of cancer. Database glossary In this sense, we conducted a systematic case–control study including genome-wide microRNA binding site SNPs.
The HPGD gene at chromosome 4q34-35 encodes a short-chain non-metalloenzyme alcohol dehydrogenase protein family. Database gale The encoded enzyme is responsible for the metabolism of prostaglandins, which function in a variety of physiologic and cellular processes, such as inflammation. Database google drive HPGD is widely distributed in various mammalian tissues such as lung, breast, prostate, placenta and gut. Database google docs Recent studies have shown a reduction of HPGD in some cancers, such as colorectal, breast, prostate, and lung , , , , . G info database Many studies have revealed that HPGD may have tumor-suppressive properties , . G info database search Ido Wolf at al. Database hosting reported that HPGD was an epigenetically silenced tumor suppressor gene in breast cancer and there was an association between HPGD expression and the ER pathway activity. Database hacking Prostaglandin E2 (PGE2) is a major stimulator of expression of aromatase, thus leading to increased synthesis of estrogen within the breast . Database history PGE2 levels are regulated not only by its synthesis but also by its degradation. Database hierarchy The key enzyme responsible for the biological inactivation of prostaglandins is NAD+-linked HPGD . Database host name Our results add another dimension to the above findings that the A allele of HPGD had a positive association with breast cancer risk, and the association was ER status specific. Database hardening SNP rs8752 (G/A) is located in the miR-485-5p binding site, and it is likely to disrupt the miR-485-5p/HPGD interaction. Database health check As shown in Figure S1 in File S1, the A allele cannot be targeted by miR-485-5p, which will result in the increase of HPGD protein expression, a possible underlying mechanism for the observed association with the risk of breast cancer.
Although, to the best of our knowledge, this is the largest systematic case-control study investigating the association between microRNA target SNPs and breast cancer risk. Database hardware Our study has several limitations. Database high availability First, we included only the SNPs with high frequency of variation, namely three genotypes with minor genotype frequency ≥0.05. Database help This strategy will inevitably miss some low frequency SNPs that associated with breast cancer risk. H2 database Second, functional studies are critical to confirm the findings of association from this study, while such studies were not performed at this stage. H2 database tutorial Third, correction for multiple comparisons was not performed in this study, although our design with large sample size and replication set can ensure a high repeatability of our findings.
In summary, our findings suggested that common variants in the HPGD gene might be associated with breast cancer risk among Chinese women. H2 database viewer Further large studies are warranted to confirm these findings and to examine the biological mechanisms for the association.
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