Exploring the association between genetic variation in the SUMO isopeptidase gene USPL1 and breast cancer through integration of data from the population-based GENICA study and external genetic databases
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Exploring the association between genetic variation in the SUMO isopeptidase gene USPL1 and breast cancer through integration of data from the population-based GENICA study and external genetic databases. / Bermejo, Justo Lorenzo; Kabisch, Maria; Dünnebier, Thomas; Schnaidt, Sven; Melchior, Frauke; Fischer, Hans-Peter; Harth, Volker; Rabstein, Sylvia; Pesch, Beate; Brüning, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Baisch, Christian; Ko, Yon-Dschun; Hamann, Ute.
In: INT J CANCER, Vol. 133, No. 2, 15.07.2013, p. 362-72.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Exploring the association between genetic variation in the SUMO isopeptidase gene USPL1 and breast cancer through integration of data from the population-based GENICA study and external genetic databases
AU - Bermejo, Justo Lorenzo
AU - Kabisch, Maria
AU - Dünnebier, Thomas
AU - Schnaidt, Sven
AU - Melchior, Frauke
AU - Fischer, Hans-Peter
AU - Harth, Volker
AU - Rabstein, Sylvia
AU - Pesch, Beate
AU - Brüning, Thomas
AU - Justenhoven, Christina
AU - Brauch, Hiltrud
AU - Baisch, Christian
AU - Ko, Yon-Dschun
AU - Hamann, Ute
N1 - Copyright © 2013 UICC.
PY - 2013/7/15
Y1 - 2013/7/15
N2 - Small ubiquitin-like modifier (SUMO) proteins are covalently attached to target proteins to modify their function. SUMO conjugation participates in processes tightly linked to tumorigenesis. Recently USPL1 (ubiquitin-specific peptidase-like (1) was identified as a SUMO isopeptidase. We report here on the first exploratory study investigating the relationship between genetic variability in USPL1 and breast cancer. Three potentially functional nonsynonymous coding SNPs (rs3742303, rs17609459, rs7984952) were genotyped in 1,021 breast cancer cases and 1,015 controls from the population-based GENICA study. We took advantage of multiple genotype imputation based on HapMap and the 1000 Genomes Project data to refine the association screening in the investigated region. Public genetic databases were also used to investigate the relationship with USPL1 expression in lymphoblastoid cell lines and breast tissue. Women homozygous for the minor C allele of rs7984952 showed a lower risk of Grade 3 breast tumors compared to TT homozygotes (OR 0.50, 95% CI 0.30-0.81). Case-only analyses confirmed the association between rs7984952 and tumor grade (OR 0.60, 95% CI 0.39-0.93). Imputation results in a 238 kb region around rs7984952 based on HapMap and the 1000 Genomes Project data were similar. No imputed variant showed an association signal stronger than rs7984952. USPL1 expression in tumor breast tissue increased with the number of C alleles. The present study illustrates the contribution of multiple imputation of genotypes using public data repositories to standard genotyping laboratory. The provided information may facilitate the design of independent studies to validate the association between USPL1 rs7984952 and risk of Grade 3 breast tumors.
AB - Small ubiquitin-like modifier (SUMO) proteins are covalently attached to target proteins to modify their function. SUMO conjugation participates in processes tightly linked to tumorigenesis. Recently USPL1 (ubiquitin-specific peptidase-like (1) was identified as a SUMO isopeptidase. We report here on the first exploratory study investigating the relationship between genetic variability in USPL1 and breast cancer. Three potentially functional nonsynonymous coding SNPs (rs3742303, rs17609459, rs7984952) were genotyped in 1,021 breast cancer cases and 1,015 controls from the population-based GENICA study. We took advantage of multiple genotype imputation based on HapMap and the 1000 Genomes Project data to refine the association screening in the investigated region. Public genetic databases were also used to investigate the relationship with USPL1 expression in lymphoblastoid cell lines and breast tissue. Women homozygous for the minor C allele of rs7984952 showed a lower risk of Grade 3 breast tumors compared to TT homozygotes (OR 0.50, 95% CI 0.30-0.81). Case-only analyses confirmed the association between rs7984952 and tumor grade (OR 0.60, 95% CI 0.39-0.93). Imputation results in a 238 kb region around rs7984952 based on HapMap and the 1000 Genomes Project data were similar. No imputed variant showed an association signal stronger than rs7984952. USPL1 expression in tumor breast tissue increased with the number of C alleles. The present study illustrates the contribution of multiple imputation of genotypes using public data repositories to standard genotyping laboratory. The provided information may facilitate the design of independent studies to validate the association between USPL1 rs7984952 and risk of Grade 3 breast tumors.
KW - Alleles
KW - Body Mass Index
KW - Breast Neoplasms
KW - Case-Control Studies
KW - Cell Line, Tumor
KW - Databases, Genetic
KW - Endopeptidases
KW - Female
KW - Gene Expression Regulation, Neoplastic
KW - Genetic Predisposition to Disease
KW - Genotype
KW - Homozygote
KW - Humans
KW - Polymorphism, Single Nucleotide
KW - Quantitative Trait Loci
KW - Regression Analysis
KW - Sequence Analysis, DNA
KW - Small Ubiquitin-Related Modifier Proteins
KW - Time Factors
KW - Ubiquitin-Specific Proteases
U2 - 10.1002/ijc.28040
DO - 10.1002/ijc.28040
M3 - SCORING: Journal article
C2 - 23338788
VL - 133
SP - 362
EP - 372
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 2
ER -