The role of genetic breast cancer susceptibility variants as prognostic factors.
نویسندگان
چکیده
Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed BC risk SNPs rs17468277 (CASP8), rs1982073 (TGFB1), rs2981582 (FGFR2), rs13281615 (8q24), rs3817198 (LSP1), rs889312 (MAP3K1), rs3803662 (TOX3), rs13387042 (2q35), rs4973768 (SLC4A7), rs6504950 (COX11) and rs10941679 (5p12) were genotyped for 25 853 BC patients with the available follow-up; 62 other SNPs, which have been suggested as BC risk SNPs by a GWAS or as candidate SNPs from individual studies, were genotyped for replication purposes in subsets of these patients. Cox proportional hazard models were used to test the association of these SNPs with overall survival (OS) and BC-specific survival (BCS). For the confirmed loci, we performed an accessory analysis of publicly available gene expression data and the prognosis in a different patient group. One of the 11 SNPs, rs3803662 (TOX3) and none of the 62 candidate/GWAS SNPs were associated with OS and/or BCS at P<0.01. The genotypic-specific survival for rs3803662 suggested a recessive mode of action [hazard ratio (HR) of rare homozygous carriers=1.21; 95% CI: 1.09-1.35, P=0.0002 and HR=1.29; 95% CI: 1.12-1.47, P=0.0003 for OS and BCS, respectively]. This association was seen similarly in all analyzed tumor subgroups defined by nodal status, tumor size, grade and estrogen receptor. Breast tumor expression of these genes was not associated with prognosis. With the exception of rs3803662 (TOX3), there was no evidence that any of the SNPs associated with BC susceptibility were associated with the BC survival. Survival may be influenced by a distinct set of germline variants from those influencing susceptibility.
منابع مشابه
Association of Obesity Related Genetic Variants (FTO and MC4R) with Breast Cancer Risk:a population-based case-control study in Iran
Background: The heterogeneous breast cancer is the most common cause of cancer-related mortality. Obesity defined by BMI is known as a major risk factor for breast cancer. Objective: The purpose of this study was to explore the role of obesity related-polymorphisms rs9939609 FTO and rs17782313 MC4R in breast cancer development. Materials and Methods: We obtained matched peripheral blood, serum ...
متن کاملRole of pathologic prognostic factors in breast cancer patients with isolated bone metastasis and relationship between SUVmax and prognostic factors
Introduction: 18F-FDG PET/CT provides very effective results in detecting metastases of breast cancer. In our study, we investigated the relationship between maximum standard uptake value (SUVmax) and prognostic pathologic factors in breast cancer cases with isolated bone metastasis and whether there was any difference in terms of prognostic pathologic factors betwee...
متن کاملGene-Gene Interaction Study Between Genetic Polymorphisms of Folate Metabolism and MTR SNPs on Prognostic Features Impact for Breast Cancer
Background: Breast Cancer (BC), the second leading cause of cancer mortality after lung cancer and varied across the world due to genetic and environmental factors. In this study, we evaluated the interaction between the polymorphisms in genes encoding enzymes of folate metabolism: methylenetetrahydrofolate reductase (MTHFR), methionine synthesis reductase (MTR) with the BC prognostic factors. ...
متن کاملSNHG6 203 Transcript Could be Applied as an Auxiliary Factor for more Precise Staging of Breast Cancer
Background: Nowadays long non-coding RNAs are known as interesting functional part of the transcriptome. LncRNA SNHG6 was reported to be expressed more in breast cancer tissues than non-tumor ones. As a frequent cancer among women, breast cancer treatment needs applied biomarkers for fast prognosis and diagnosis. SNHG6 RNA and its splice variants could be considered as molecula...
متن کاملReview on the role of host genetic factors in the susceptibility to SARS-CoV-2
Background: Severe acute respiratory system Cov-2 pandemic has affected the world populations for more than one year. Different incidence and severity of this viral disease among various age range and individuals with different background disease may indicate the pivotal role of host genetic factors in their prevalence and mortality rate. In this regards, present study was performed to review t...
متن کاملComparative study of chemo-sensitivity expressed as micronuclei in lymphocytes of breast cancer patients, their unaffected first degree relatives and normal controls as a possible prognostic marker
Background: Genomic instability is one of primary causes for malignant cell transformation. In this study induced genomic instability expressed as micronuclei in breast cancer (BC) patients with different stages of the disease compared with their unaffected first degree relatives (FDR) and normal unrelated controls was investigated. Materials and Methods: The background and net micronucleus fre...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Human molecular genetics
دوره 21 17 شماره
صفحات -
تاریخ انتشار 2012