TY - JOUR
T1 - Germline copy number variation and ovarian cancer survival
AU - Fridley, Brooke L.
AU - Chalise, Prabhakar
AU - Tsai, Ya Yu
AU - Sun, Zhifu
AU - Vierkant, Robert A.
AU - Larson, Melissa C.
AU - Cunningham, Julie M.
AU - Iversen, Edwin S.
AU - Fenstermacher, David
AU - Barnholtz-Sloan, Jill
AU - Asmann, Yan
AU - Risch, Harvey A.
AU - Schildkraut, Joellen M.
AU - Phelan, Catherine M.
AU - Sutphen, Rebecca
AU - Sellers, Thomas A.
AU - Goode, Ellen L.
N1 - Funding Information:
Work in the laboratory is supported in part by Grants AI 19042, CA 16858, CA 22736, and CA 13696 from the National Institutes of Health and by a grant from Becton Dickinson. S.-U.S. is supported by the Cancer Research Institute/J. M. Foundation Fellowship.
PY - 2012
Y1 - 2012
N2 - Copy number variants (CNVs) have been implicated in many complex diseases.We examined whether inherited CNVs were associated with overall survival among women with invasive epithelial ovarian cancer. Germline DNA from 1,056 cases (494 deceased, average of 3.7 years follow-up) was interrogated with the Illumina 610 quad genome-wide array containing, after quality control exclusions, 581,903 single nucleotide polymorphisms (SNPs) and 17,917 CNV probes. Comprehensive analysis capitalized upon the strengths of three complementary approaches to CNV classification. First, to identify small CNVs, single markers were evaluated and, where associated with survival, consecutive markers were combined. Two chromosomal regions were associated with survival using this approach (14q31.3 rs2274736 p=1.59×10-6, p=0.001; 22q13.31 rs2285164 p =4.01×10-5, p=0.009), but were not significant after multiple testing correction. Second, to identify large CNVs, genome-wide segmentation was conducted to characterize chromosomal gains and losses, and association with survival was evaluated by segment. Four regions were associated with survival (1q21.3 loss p=0.005, 5p14.1 loss p=0.004, 9p23 loss p=0.002, and 15q22.31 gain p=0.002); however, again, after correcting for multiple testing, no regions were statistically significant, and none were in common with the single marker approach. Finally, to evaluate associations with general amounts of copy number changes across the genome, we estimated CNV burden based on genome-wide numbers of gains and losses; no associations with survival were observed (p >0.40). Although CNVs that were not well-covered by the Illumina 610 quad array merit investigation, these data suggest no association between inherited CNVs and survival after ovarian cancer.
AB - Copy number variants (CNVs) have been implicated in many complex diseases.We examined whether inherited CNVs were associated with overall survival among women with invasive epithelial ovarian cancer. Germline DNA from 1,056 cases (494 deceased, average of 3.7 years follow-up) was interrogated with the Illumina 610 quad genome-wide array containing, after quality control exclusions, 581,903 single nucleotide polymorphisms (SNPs) and 17,917 CNV probes. Comprehensive analysis capitalized upon the strengths of three complementary approaches to CNV classification. First, to identify small CNVs, single markers were evaluated and, where associated with survival, consecutive markers were combined. Two chromosomal regions were associated with survival using this approach (14q31.3 rs2274736 p=1.59×10-6, p=0.001; 22q13.31 rs2285164 p =4.01×10-5, p=0.009), but were not significant after multiple testing correction. Second, to identify large CNVs, genome-wide segmentation was conducted to characterize chromosomal gains and losses, and association with survival was evaluated by segment. Four regions were associated with survival (1q21.3 loss p=0.005, 5p14.1 loss p=0.004, 9p23 loss p=0.002, and 15q22.31 gain p=0.002); however, again, after correcting for multiple testing, no regions were statistically significant, and none were in common with the single marker approach. Finally, to evaluate associations with general amounts of copy number changes across the genome, we estimated CNV burden based on genome-wide numbers of gains and losses; no associations with survival were observed (p >0.40). Although CNVs that were not well-covered by the Illumina 610 quad array merit investigation, these data suggest no association between inherited CNVs and survival after ovarian cancer.
KW - Association testing
KW - Copy number variation
KW - Genotyping array
KW - Ovarian cancer
KW - Overall survival
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U2 - 10.3389/fgene.2012.00142
DO - 10.3389/fgene.2012.00142
M3 - Article
C2 - 22891074
AN - SCOPUS:84876144579
SN - 1664-8021
VL - 3
JO - Frontiers in Genetics
JF - Frontiers in Genetics
IS - AUG
M1 - Article 142
ER -