Ontology highlight
ABSTRACT:
Methods: To identify variants associated with a breast-colorectal cancer phenotype, we analyzed genome-wide association study (GWAS) data from cases and controls that met the following criteria: cases (n = 985) were women with breast cancer who had one or more first- or second-degree relatives with colorectal cancer, men/women with colorectal cancer who had one or more first- or second-degree relatives with breast cancer, and women diagnosed with both breast and colorectal cancer. Controls (n = 1769), were unrelated, breast and colorectal cancer-free, and age- and sex- frequency-matched to cases. After imputation, 6,220,060 variants were analyzed using the discovery set and variants associated with the breast-colorectal cancer phenotype at P<5.0E-04 (n = 549, at 60 loci) were analyzed for replication (n = 293 cases and 2,103 controls).
Results: Multiple correlated SNPs in intron 1 of the ROBO1 gene were suggestively associated with the breast-colorectal cancer phenotype in the discovery and replication data (most significant; rs7430339, Pdiscovery = 1.2E-04; rs7429100, Preplication = 2.8E-03). In meta-analysis of the discovery and replication data, the most significant association remained at rs7429100 (P = 1.84E-06).
Conclusion: The results of this exploratory analysis did not find clear evidence for a susceptibility locus with a pleiotropic effect on hereditary breast and colorectal cancer risk, although the suggestive association of genetic variation in the region of ROBO1, a potential tumor suppressor gene, merits further investigation.
SUBMITTER: Pande M
PROVIDER: S-EPMC5919670 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Pande Mala M Joon Aron A Brewster Abenaa M AM Chen Wei V WV Hopper John L JL Eng Cathy C Shete Sanjay S Casey Graham G Schumacher Fredrick F Lin Yi Y Harrison Tabitha A TA White Emily E Ahsan Habibul H Andrulis Irene L IL Whittemore Alice S AS John Esther M EM Ko Win Aung A Makalic Enes E Schmidt Daniel F DF Kapuscinski Miroslaw K MK Ochs-Balcom Heather M HM Gallinger Steven S Jenkins Mark A MA Newcomb Polly A PA Lindor Noralane M NM Peters Ulrike U Amos Christopher I CI Lynch Patrick M PM
PloS one 20180426 4
<h4>Background</h4>Clustering of breast and colorectal cancer has been observed within some families and cannot be explained by chance or known high-risk mutations in major susceptibility genes. Potential shared genetic susceptibility between breast and colorectal cancer, not explained by high-penetrance genes, has been postulated. We hypothesized that yet undiscovered genetic variants predispose to a breast-colorectal cancer phenotype.<h4>Methods</h4>To identify variants associated with a breas ...[more]