Genome-Wide Comparison of Copy Number Variations in Finnish Familial Prostate and Breast Cancers
AKINRINADE, OYEDIRAN (2012)
AKINRINADE, OYEDIRAN
2012
Bioinformatiikka - Bioinformatics
Biolääketieteellisen teknologian yksikkö - Institute of Biomedical Technology
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Hyväksymispäivämäärä
2012-06-11
Julkaisun pysyvä osoite on
https://urn.fi/urn:nbn:fi:uta-1-22737
https://urn.fi/urn:nbn:fi:uta-1-22737
Tiivistelmä
Abstract
Background and aims: Prostate and breast cancers are the most prevalent types of cancer in all Western countries including Finland. For both cancer types, there is a “missing heritability” - the genetic defects predisposing individuals to the cancers remain unknown. Copy number variations (CNVs) have recently been implicated in predisposition to complex diseases including cancer. To this end, this genome-wide association study was aimed at evaluating the role of CNV in prostate and breast cancer susceptibility in the Finnish population.
Methods: Four algorithms were used in identifying CNVs in Illumina genotyped prostate and breast cancer samples; called CNVs were compared with CNVs published in the Database of Genomic Variants (DGV) in order to identify novel CNVs. Genes located within or close to the regions of CNVs were queried against the genes listed in OMIM to identify CNVs which warrant further investigation. Case-control association test was carried out using Fisher’s exact test to identify CNVs associated with the cancer types in question.
Results:A total of 359 and 764 CNVs were identified in the breast and prostate cancers datasets, respectively; while the average number of CNVs per sample is higher in the prostate cancer (male genome), the size of CNVs in breast cancer dataset is double the size in prostate cancer. Three susceptibility loci were associated to prostate cancer: 2p25.3, 3p26.1 and 10q11.22. While 3p26 has previously been reported, 2p25.3 and 10q11.22 are novel. Several of the genes affected by CNVs in the datasets had already been implicated in different cancers.
Conclusion:This study is the first to compare CNVs in male and female genomes. The data suggests that several genes located within the identified CNVs may contribute to cancer predisposition in this small cohort of samples, and this trend needs to be confirmed in larger population samples.
Background and aims: Prostate and breast cancers are the most prevalent types of cancer in all Western countries including Finland. For both cancer types, there is a “missing heritability” - the genetic defects predisposing individuals to the cancers remain unknown. Copy number variations (CNVs) have recently been implicated in predisposition to complex diseases including cancer. To this end, this genome-wide association study was aimed at evaluating the role of CNV in prostate and breast cancer susceptibility in the Finnish population.
Methods: Four algorithms were used in identifying CNVs in Illumina genotyped prostate and breast cancer samples; called CNVs were compared with CNVs published in the Database of Genomic Variants (DGV) in order to identify novel CNVs. Genes located within or close to the regions of CNVs were queried against the genes listed in OMIM to identify CNVs which warrant further investigation. Case-control association test was carried out using Fisher’s exact test to identify CNVs associated with the cancer types in question.
Results:A total of 359 and 764 CNVs were identified in the breast and prostate cancers datasets, respectively; while the average number of CNVs per sample is higher in the prostate cancer (male genome), the size of CNVs in breast cancer dataset is double the size in prostate cancer. Three susceptibility loci were associated to prostate cancer: 2p25.3, 3p26.1 and 10q11.22. While 3p26 has previously been reported, 2p25.3 and 10q11.22 are novel. Several of the genes affected by CNVs in the datasets had already been implicated in different cancers.
Conclusion:This study is the first to compare CNVs in male and female genomes. The data suggests that several genes located within the identified CNVs may contribute to cancer predisposition in this small cohort of samples, and this trend needs to be confirmed in larger population samples.