https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 Evaluation of associations between genetically predicted circulating protein biomarkers and breast cancer risk https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37129 via the integration of genomics and proteomics data. In the Breast Cancer Association Consortium (BCAC), with 122,977 cases and 105,974 controls of European descendants, we evaluated the associations of the genetically predicted concentrations of >1,400 circulating proteins with breast cancer risk. We used data from a large-scale protein quantitative trait loci (pQTL) analysis as our study instrument. Summary statistics for these pQTL variants related to breast cancer risk were obtained from the BCAC and used to estimate odds ratios (OR) for each protein using the inverse-variance weighted method. We identified 56 proteins significantly associated with breast cancer risk by instrumental analysis (false discovery rate <0.05). Of these, the concentrations of 32 were influenced by variants close to a breast cancer susceptibility locus (ABO, 9q34.2). Many of these proteins, such as insulin receptor, insulin-like growth factor receptor 1 and other membrane receptors (OR: 0.82-1.18, p values: 6.96 × 10-43.28 × 10-8), are linked to insulin resistance and estrogen receptor signaling pathways. Proteins identified at other loci include those involved in biological processes such as alcohol and lipid metabolism, proteolysis, apoptosis, immune regulation and cell motility and proliferation. Consistent associations were observed for 22 proteins in the UK Biobank data (p < 0.05). The study identifies potential novel biomarkers for breast cancer, but further investigation is needed to replicate our findings.]]> Wed 19 Aug 2020 12:59:44 AEST ]]> Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk. https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20561 Wed 11 Apr 2018 15:36:46 AEST ]]> Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26195 Wed 11 Apr 2018 15:00:42 AEST ]]> Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19379 Wed 11 Apr 2018 14:19:24 AEST ]]> PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29559 G and c.3113G > A, CHEK2 c.349A > G, c.538C > T, c.715G > A, c.1036C > T, c.1312G > T, and c.1343T > G and ATM c.7271T > G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10-5), PALB2 c.3113G > A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10-8) and ATM c.7271T > G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A > G OR 2.26 (95% CI 1.29 to 3.95), c.1036C > T OR 5.06 (95% CI 1.09 to 23.5) and c.538C > T OR 1.33 (95% CI 1.05 to 1.67) (p=0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T > G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G > T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.]]> Wed 11 Apr 2018 10:43:09 AEST ]]> Candidate locus analysis of the TERT-CLPTM1L cancer risk region on chromosome 5p15 identifies multiple independent variants associated with endometrial cancer risk https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28088 −6 to P = 7.7 × 10−5). Only one falls into a haplotype previously associated with other cancer types (rs7705526, in TERT intron 1), and this SNP has been shown to alter TERT promoter activity. One of the novel associations (rs13174814) maps to a second region in the TERT promoter and the other (rs62329728) is in the promoter region of CLPTM1L; neither are correlated with previously reported cancer-associated SNPs. Using TCGA RNASeq data, we found significantly increased expression of both TERT and CLPTM1L in endometrial cancer tissue compared with normal tissue (TERTP = 1.5 × 10−18, CLPTM1LP = 1.5 × 10−19). Our study thus reports a novel endometrial cancer risk locus and expands the spectrum of cancer types associated with genetic variation at 5p15, further highlighting the importance of this region for cancer susceptibility.]]> Wed 11 Apr 2018 09:49:25 AEST ]]> Polymorphisms in a putative enhancer at the 10q21.2 breast cancer risk locus regulate NRBF2 expression https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28231 Wed 01 Aug 2018 14:52:20 AEST ]]> Genome-wide association study identifies a possible susceptibility locus for endometrial cancer https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17481 Sat 24 Mar 2018 08:04:10 AEDT ]]> Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20582 Sat 24 Mar 2018 07:55:36 AEDT ]]> Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26799 Sat 24 Mar 2018 07:36:26 AEDT ]]> Genetic risk score mendelian randomization shows that obesity measured as body mass index, but not waist:hip ratio, is causal for endometrial cancer https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30306 Sat 24 Mar 2018 07:31:48 AEDT ]]>