Citations 12
MicroRNA Processing and Binding Site Polymorphisms Are Not Replicated in the Ovarian Cancer Association Consortium
Permuth‐Wey, Jennifer, Chen, Zhihua , Lin, Hui‐Yi , Chen, Y. Ann , Barnholtz‐Sloan, Jill S. , Birrer, Michael J. , Cunningham, Julie M. , Fenstermacher, David, García‐Closas, Montserrat , Gayther, Simon A. , Bosquet, Jesús González , Iversen, Edwin S., McLaughlin, John, Menon, Usha , Narod, Steven A., Phelan, Catherine M., Ramus, Susan J. , Song, Honglin , Sutphen, Rebecca , Terry, Kathryn L. , Vierkant, Robert A. , Wentzensen, Nicolas , Lancaster, Johnathan M., Cheng, Jin Q. , Schildkraut, Joellen M. , Goode, Ellen L. , Sellers, Thomas A., Tsai, Ya-Yu , Chanock, Stephen Jacob , Cramer, Daniel W. , Fridley, Brooke L. , Gentry‐Maharaj, Aleksandra , Jim, Heather , McLaughlin, John, Risch, Harvey A. , Tyrer, Jonathan P. , Berchuck, Andrew , Pharoah, Paul D.P. , Ramus, Susan J , Vierkant, Robert A , Menon, Usha , Barnholtz-Sloan, Jill S , Lin, Hui-Yi , García-Closas, Montserrat , Bosquet, Jesus Gonzalez
Cancer Epidemiology, Biomarkers & Prevention | August 8, 2011 | Volume: 20 | Issue: 8 | Pages: 1793-1797
Abstract Background: Single nucleotide polymorphisms (SNP) in microRNA-related genes have been associated with epithelial ovarian cancer (EOC) risk in two reports, yet associated alleles may be inconsistent across studies. Methods: We conducted a pooled analysis of previously identified SNPs by combining genotype data from 3,973 invasive EOC cases and 3,276 controls from the Ovarian Cancer Association Consortium. We also conducted imputation to obtain dense coverage of genes and comparable genotype data for all studies. In total, 226 SNPs within 15 kb of 4 miRNA biogenesis genes (DDX20, DROSHA, GEMIN4, and XPO5) and 23 SNPs located within putative miRNA binding sites of 6 genes (CAV1, COL18A1, E2F2, IL1R1, KRAS, and UGT2A3) were genotyped or imputed and analyzed in the entire dataset. Results: After adjustment for European ancestry, no overall association was observed between any of the analyzed SNPs and EOC risk. Conclusions: Common variants in these evaluated genes do not seem to be strongly associated with EOC risk. Impact: This analysis suggests earlier associations between EOC risk and SNPs in these genes may have been chance findings, possibly confounded by population admixture. To more adequately evaluate the relationship between genetic variants and cancer risk, large sample sizes are needed, adjustment for population stratification should be carried out, and use of imputed SNP data should be considered. Cancer Epidemiol Biomarkers Prev; 20(8); 1793–7. ©2011 AACR.
LIN28B Polymorphisms Influence Susceptibility to Epithelial Ovarian Cancer
Permuth‐Wey, Jennifer, Tsai, Ya-Yu, Lin, Hui‐Yi , Chen, Y. Ann , Barnholtz‐Sloan, Jill S. , Birrer, Michael J. , Bloom, Gregory, Chen, Zhihua , Cunningham, Julie M. , Dagne, Getachew , Ebbert-Syfrett, Judith, Fenstermacher, David, García‐Closas, Montserrat , Gayther, Simon A. , Bosquet, Jesús González , Goode, Ellen L. , Iversen, Edwin S., Kong, William, McLaughlin, John, Menon, Usha , Monteiro, Álvaro N.A. , Narod, Steven A., Phelan, Catherine M., Qu, Xiaotao , Ramus, Susan J. , Schildkraut, Joellen M. , Song, Honglin , Stockwell, Heather, Sutphen, Rebecca , Terry, Kathryn L. , Vierkant, Robert A. , Wentzensen, Nicolas , Lancaster, Johnathan M., Cheng, Jin Q. , Sellers, Thomas A. , Kim, Donghwa , Chanock, Stephen Jacob , Cramer, Daniel W. , Fridley, Brooke L. , Ge, William H. , Gentry‐Maharaj, Aleksandra , Jim, Heather , McLaughlin, John, Pharoah, Paul D.P. , Risch, Harvey A. , Tyrer, Jonathan P. , Ramus, Susan J , Vierkant, Robert A , Menon, Usha , Monteiro, Alvaro N , Barnholtz-Sloan, Jill S , Lin, Hui-Yi , García-Closas, Montserrat , Bosquet, Jesus Gonzalez
Cancer Research | April 12, 2011 | Volume: 71 | Issue: 11 | Pages: 3896-3903
Abstract Defective microRNA (miRNA) biogenesis contributes to the development and progression of epithelial ovarian cancer (EOC). In this study, we examined the hypothesis that single nucleotide polymorphisms (SNP) in miRNA biogenesis genes may influence EOC risk. In an initial investigation, 318 SNPs in 18 genes were evaluated among 1,815 EOC cases and 1,900 controls, followed up by a replicative joint meta-analysis of data from an additional 2,172 cases and 3,052 controls. Of 23 SNPs from 9 genes associated with risk (empirical P < 0.05) in the initial investigation, the meta-analysis replicated 6 SNPs from the DROSHA, FMR1, LIN28, and LIN28B genes, including rs12194974 (G>A), an SNP in a putative transcription factor binding site in the LIN28B promoter region (summary OR = 0.90, 95% CI: 0.82–0.98; P = 0.015) which has been recently implicated in age of menarche and other phenotypes. Consistent with reports that LIN28B overexpression in EOC contributes to tumorigenesis by repressing tumor suppressor let-7 expression, we provide data from luciferase reporter assays and quantitative RT-PCR to suggest that the inverse association among rs12194974 A allele carriers may be because of reduced LIN28B expression. Our findings suggest that variants in LIN28B and possibly other miRNA biogenesis genes may influence EOC susceptibility. Cancer Res; 71(11); 3896–903. ©2011 AACR.