title: Polymorphisms in the UBC9 and PIAS3 genes of the SUMO-conjugating system and breast cancer risk.
abstract: SUMOylation consists in the covalent conjugation of small ubiquitin-related modifiers to target proteins. SUMOylation participates in processes that are tightly linked to tumorigenesis, and genetic variability in the SUMO-conjugating system may influence the development of breast cancer. We recently reported that variation in the UBC9 gene encoding the SUMO-conjugating enzyme may affect the grade of breast tumors. Following comprehensive in silico analyses for detection of putative functional polymorphisms in 14 genes of the SUMO system, we selected one coding SNP in PIAS3 and seven tag SNPs in UBC9 for association analyses. Results were based on 1,021 cases, and 1,015 matched controls from the population-based GENICA study. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by conditional logistic regression. To explore the association with polymorphisms closely linked to the genotyped variants, multiple imputation based on HapMap data was applied. The study revealed associations of four UBC9 polymorphisms with risk of grade 1 tumors. Comparison of genotype and haplotype models indicated that the best representation of risk solely relied on rs7187167 under dominant penetrance. Women carrying the rare allele showed an increased risk of grade 1 tumors compared with common homozygotes (OR 1.87, 95% CI 1.18-2.95). This effect appeared to be stronger in women with a family history of breast or ovarian cancer. Imputation of polymorphisms in a 300-kb region around the genotyped polymorphisms identified no variants with stronger associations. Our findings suggest that genetic variation in UBC9 may affect the risk of grade 1 breast tumors.
authors.affiliation: Molecular Genetics of Breast Cancer (B055), Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dünnebier
authors.forename: Justo Lorenzo
authors.initials: JL
authors.lastname: Bermejo
authors.forename: Susanne
authors.initials: S
authors.lastname: Haas
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Fischer
authors.forename: Christiane B
authors.initials: CB
authors.lastname: Pierl
authors.forename: Christina
authors.initials: C
authors.lastname: Justenhoven
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Brauch
authors.forename: Christian
authors.initials: C
authors.lastname: Baisch
authors.forename: Michael
authors.initials: M
authors.lastname: Gilbert
authors.forename: Volker
authors.initials: V
authors.lastname: Harth
authors.forename: Anne
authors.initials: A
authors.lastname: Spickenheuer
authors.forename: Sylvia
authors.initials: S
authors.lastname: Rabstein
authors.forename: Beate
authors.initials: B
authors.lastname: Pesch
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
authors.forename: Yon-Dschun
authors.initials: YD
authors.lastname: Ko
authors.forename: Ute
authors.initials: U
authors.lastname: Hamann
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D018832:Molecular Chaperones; C484745:PIAS3 protein, human; D050828:Protein Inhibitors of Activated STAT; D025842:SUMO-1 Protein; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9