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  • GENOME-WIDE ASSOCIATION  (6)
  • Life and Medical Sciences  (6)
  • Phaseolus vulgaris  (6)
  • Cell & Developmental Biology  (5)
  • Bemisia argentifolii  (3)
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  • 1
    Keywords: EXPRESSION ; tumor ; POPULATION ; chromosome ; LYMPHOCYTES ; OUTCOMES ; LOCUS ; GENOME-WIDE ASSOCIATION ; CONFER SUSCEPTIBILITY ; COMMON VARIANTS
    Abstract: Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2p36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 x 10(-9)). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.
    Type of Publication: Journal article published
    PubMed ID: 24937182
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  • 2
    Keywords: EXPRESSION ; REDUCED RISK ; HUMAN GENES ; SINGLE-NUCLEOTIDE POLYMORPHISMS ; BINDING-SITES ; COMMON VARIANT ; CASP8 GENE ; susceptibility loci ; GENOME-WIDE ASSOCIATION ; IDENTIFIES 3
    Abstract: Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.
    Type of Publication: Journal article published
    PubMed ID: 25390939
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  • 3
    Keywords: PROSTATE ; prevention ; WOMEN ; SUBTYPES ; FAMILY-HISTORY ; susceptibility loci ; GENOME-WIDE ASSOCIATION ; CONSORTIUM
    Abstract: BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.
    Type of Publication: Journal article published
    PubMed ID: 25855707
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  • 4
    Keywords: carcinoma ; fibroblasts ; METAANALYSIS ; susceptibility loci ; GENOME-WIDE ASSOCIATION ; REVERSE-TRANSCRIPTASE HTERT ; GENETIC-VARIATION ; COMMON VARIANTS ; TERT-CLPTM1L LOCUS ; BUCCAL CELLS
    Abstract: TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 x 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 x 10(-8)) and BRCA1 mutation carrier (P = 1.1 x 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 x 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 x 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 x 10(-12)) and BRCA1 mutation carrier (P = 1.6 x 10-14) breast and invasive ovarian (P = 1.3 x 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.
    Type of Publication: Journal article published
    PubMed ID: 23535731
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  • 5
    Keywords: EXPRESSION ; GENE ; SIGNALING PATHWAY ; susceptibility loci ; GENOME-WIDE ASSOCIATION ; HORMONE-RELATED PROTEIN ; CONSORTIUM ; CONFER SUSCEPTIBILITY ; COMMON VARIANTS ; 14Q24.1 RAD51L1
    Abstract: Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for similar to 9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P 〈 5 x 10(-8)). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility.
    Type of Publication: Journal article published
    PubMed ID: 23535729
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  • 6
    Keywords: LUNG-CANCER ; polymorphism ; PROGRESSION ; AMPLIFICATION ; PROSTATE-CANCER ; CELL-DIVISION ; GENOME-WIDE ASSOCIATION ; CANCER SUSCEPTIBILITY LOCI ; RISK LOCI ; TACC2
    Abstract: Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymorphisms (SNPs) from 194 mitotic genes and breast cancer risk, overall and by histologic grade, in the Breast Cancer Association Consortium (BCAC) iCOGS study (n = 39 067 cases; n = 42 106 controls). SNPs in TACC2 [rs17550038: odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16-1.33, P = 4.2 x 10(-10)) and EIF3H (rs799890: OR = 1.07, 95% CI 1.04-1.11, P = 8.7 x 10(-6)) were significantly associated with risk of low-grade breast cancer. The TACC2 signal was retained (rs17550038: OR = 1.15, 95% CI 1.07-1.23, P = 7.9 x 10(-5)) after adjustment for breast cancer risk SNPs in the nearby FGFR2 gene, suggesting that TACC2 is a novel, independent genome-wide significant genetic risk locus for low-grade breast cancer. While no SNPs were individually associated with high-grade disease, a pathway-level gene set analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk (P = 2.1 x 10(-3)). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer.
    Type of Publication: Journal article published
    PubMed ID: 24927736
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Theoretical and applied genetics 62 (1982), S. 361-367 
    ISSN: 1432-2242
    Keywords: Phaseolus vulgaris ; Lectins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The relationship between the polypeptide composition and the agglutination behaviour of the lectin-containing G2/albumin protein groups has allowed the identification of the active lectin polypeptides in different cultivars of Phaseolus vulgaris (Brown et al. accompanying paper). These results were used to ascertain the particular G2/albumin group contained in the various lectin sources used previously for the purification of lectin proteins. Many studies were found to have included lectin sources which contained the same G2/albumin pattern (TG2) and this common denominator has permitted the direct comparison of the properties reported for these purified lectins. Thus, much of the extensive literature on bean lectins is concurred.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Theoretical and applied genetics 70 (1985), S. 22-31 
    ISSN: 1432-2242
    Keywords: Phaseolus vulgaris ; Lectin ; Phaseolin ; Quantitative variation ; Immunoelectrophoresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Seeds of forty bean cultivars having different lectin types based on two-dimensional isoelectric focusing-sodium dodecyl sulfate polyacrylamide gel electrophoresis (IEF-SDS/PAGE) were analyzed for quantities of lectin, phaseolin and total protein. Significant differences were found among groups of cultivars with different lectin types for the quantity of lectin and phaseolin. Cultivars with more complex lectin types based on IEF-SDS/PAGE tended to have higher quantities of lectin and lower quantities of phaseolin than cultivars with simple lectin types. An association between lectin type and the quantity of lectin and phaseolin was found also in the seeds of F2 plants that segregated in a Mendelian fashion for two lectin types. Seeds from plants with the complex lectin type had more lectin and less phaseolin than seeds from plants with the simple lectin type. Therefore, the genes controlling qualitative lectin variation also may influence the quantitative variation of lectin and phaseolin. The results of this study are related to other studies on the quantitative variation for seed proteins and to the possible molecular basis for variation in the quantity of lectins in beans.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2242
    Keywords: Phaseolus vulgaris ; Phaseolin ; Seed proteins ; Electrophoresis ; Linkage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The inheritance of phaseolin and globulin-2 (G2)/albumin polypeptides was investigated in crosses involving varieties which exhibited the three electrophoretic banding patterns of phaseolin found in French bean. ‘Total’ seed protein extracts of single seeds of the F1 and F2 generations from the crosses: ‘Sanilac’ × ‘Contender’, ‘BBL 240’ × ‘Contender’, and ‘Sanilac’ × ‘BBL 240’ were analyzed by two-dimensional electrophoresis. Segregation of the genes controlling phaseolin and G2/albumin polypeptides, and those controlling a further five groups of seed proteins (A, B, D, E, and F) were observed. No recombinant electrophoretic phenotypes were seen for phaseolin or G2/albumin polypeptides suggesting that the genes controlling each of these groups of polypeptides are closely linked and segregate like single Mendelian genes. The phaseolin genes and G2/albumin genes were not linked to each other. The group of genes controlling phaseolin polypeptides were linked to those controlling group B proteins, and those controlling G2/albumin polypeptides were linked to those controlling group F proteins.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-2242
    Keywords: Phaseolus vulgaris ; Lectins ; Albumin ; Globulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Variation in the native conformation of bean lectins was examined using electrophoresis of non-denatured total protein extracts and purified albumin and globulin lectin. The observed variation was related to the genetic variation reported previously for lectin polypeptide composition as revealed by two-dimensional isoelectricfocusing-sodium dodecyl sulfate polyacrylamide gel electrophoresis (IEF-SDS/PAGE). When eleven cultivars with different IEF-SDS/PAGE lectin polypeptide compositions were compared, eight had unique non-denatured lectin patterns and three had identical patterns. For some cultivars differences in non-denatured lectin patterns were observed between the purified albumin and globulin lectin preparations.
    Type of Medium: Electronic Resource
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