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  • POPULATION  (3)
  • 1
    Keywords: RECEPTOR ; CANCER ; POPULATION ; RISK ; SITE ; DISTINCT ; GENE ; GENES ; GENOME ; RESOLUTION ; BINDING ; SEQUENCE ; ASSOCIATION ; SUSCEPTIBILITY ; SUSCEPTIBILITY LOCUS ; ALPHA ; BREAST ; breast cancer ; BREAST-CANCER ; genetics ; SNP ; POPULATIONS ; PROJECT ; ESTROGEN-RECEPTOR ; HETEROGENEITY ; ORIGIN ; TAMOXIFEN ; ASSOCIATIONS ; SNPs ; SCIENCE ; ESTROGEN ; HAPLOTYPE ; LOCUS ; TRAITS ; estrogen receptor ; BINDING-SITE ; CHINESE POPULATION ; GENOME-WIDE ASSOCIATION ; AFRICAN-AMERICAN ; ESTROGEN-RECEPTOR-ALPHA ; CONFER SUSCEPTIBILITY ; BINDING SITE ; Genetic ; COMMON VARIANTS ; ANCESTRY ; PANEL ; CAUSAL VARIANTS
    Abstract: We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1) genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case: control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively). Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2x10(-3)), African (OR = 1.35, P = 0.014), and Asian (OR = 1.23, P = 2.9x10(-4)) population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9x10(-7)), was without significant heterogeneity between ancestries (P-het = 0.36) and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[ T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268), which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping
    Type of Publication: Journal article published
    PubMed ID: 20661439
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  • 2
    Keywords: CANCER ; SURVIVAL ; CLASSIFICATION ; DIAGNOSIS ; FOLLOW-UP ; DEATH ; DISEASE ; POPULATION ; PROTEIN ; PROTEINS ; PATIENT ; MARKER ; prognosis ; BIOMARKERS ; CYCLE ; STAGE ; IDENTIFICATION ; colorectal cancer ; COLORECTAL-CANCER ; mass spectrometry ; SPECTROMETRY ; chemotherapy ; MARKERS ; MASS-SPECTROMETRY ; SURFACE ; NETHERLANDS ; PROTEOMIC ANALYSIS ; ONCOLOGY ; monitoring ; overall survival ; MS ; biomarker ; PROFILES ; colorectal ; PROFILE ; STAGE OVARIAN-CANCER ; TREATMENT RESPONSE ; transthyretin ; Follow up ; APOLIPOPROTEIN A1 ; prognostic ; proteomic
    Abstract: Colorectal cancer (CRC) is the second most common cause of cancer related death. Prognosis is highly dependent on stage at diagnosis making early detection mandatory. This study aimed to identify novel disease specific biomarkers of CRC, validate our previously identified biomarkers of CRC and identify serum biomarkers predicting treatment response and for monitoring. Serum of patients with metastatic CRC was collected, according to a predefined schedule, prior to start of standard first-line chemotherapy with oxaliplatin and capecitabine and serially before each 3 weekly treatment cycle and analyzed for proteomic profile by standardized SELDI-TOF MS. Serum proteomic mass spectrometry data of all subjects were processed using the tbimass R-package and proteomic profiles of CRC patients were compared with those of matched normal control subjects. Furthermore, changes in proteomic profiles during the course of chemotherapy were recorded according to treatment response. In total, 42 patients with advanced CRC were treated and mean follow-up was 13.5 months. The response rate was 50% and the median overall survival 19.5 months (95% CI: 16-23). By comparing CRC patients and healthy controls we identified 13 potential biomarkers of CRC (m/z 2.0-31.9 kDa) whereas two proteins, m/z 14060 and 28100 Da (apolipoprotein A-I), were highly significant (p〈0.0001). Comparison of responding and non-responding patients identified 6 proteins potentially predicting response, where of m/z 3330 Da was significant (p=0.007). Serial analysis identified 2 proteins, m/z 2022 and 28100 Da, that changed during chemotherapy in accordance with response. We identified 13 m/z values discriminating between CRC patients and healthy controls, including the previously identified apolipoprotein A-I as a candidate biomarker for CRC and treatment monitoring
    Type of Publication: Journal article published
    PubMed ID: 20514444
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  • 3
    Keywords: SPECTRA ; carcinoma ; CELL ; NEW-YORK ; POPULATION ; RISK ; RISK-FACTORS ; SKIN ; ASSOCIATION ; polymorphism ; SUSCEPTIBILITY ; VARIANTS ; ACID ; genetics ; MELANOMA ; POPULATIONS ; INDIVIDUALS ; heredity ; MELANOCORTIN-1 RECEPTOR MC1R ; basal cell carcinoma ; CELL CARCINOMA ; VARIANT ; INCREASE ; hair ; HAPLOTYPE ; NONMELANOMA SKIN-CANCER ; USA ; PIGMENTATION ; INCREASES ; GENOME-WIDE ASSOCIATION ; association study ; BASAL-CELL ; CONFERS RISK ; AGOUTI ; EYE-COLOR ; GENE VARIANTS ; MC1R
    Abstract: Fair color increases risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC). Recent genome-wide association studies have identified variants affecting hair, eye and skin pigmentation in Europeans. Here, we assess the effect of these variants on risk of CM and BCC in European populations comprising 2,121 individuals with CM, 2,163 individuals with BCC and over 40,000 controls. A haplotype near ASIP, known to affect a similar spectrum of pigmentation traits as MC1R variants, conferred significant risk of CM (odds ratio (OR) 1.45, P = 1.2 x 10(-9)) and BCC (OR = 1.33, P = 1.2 x 10(-6)). The variant in TYR encoding the R402Q amino acid substitution, previously shown to affect eye color and tanning response, conferred risk of CM (OR = 1.21, P = 2.8 x 10(-7)) and BCC (OR = 1.14, P = 6.1 x 10(-4)). An eye color variant in TYRP1 was associated with risk of CM (OR = 1.15, P = 4.6 x 10(-4)). The association of all three variants is robust with respect to adjustment for the effect of pigmentation
    Type of Publication: Journal article published
    PubMed ID: 18488027
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