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Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium
The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group
2009
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634713/ https://www.ncbi.nlm.nih.gov/pubmed/19127255 http://dx.doi.org/10.1038/sj.bjc.6604820 |
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| author | Pearce, C L Near, A M Van Den Berg, D J Ramus, S J Gentry-Maharaj, A Menon, U Gayther, S A Anderson, A R Edlund, C K Wu, A H Chen, X Beesley, J Webb, P M Holt, S K Chen, C Doherty, J A Rossing, M A Whittemore, A S McGuire, V DiCioccio, R A Goodman, M T Lurie, G Carney, M E Wilkens, L R Ness, R B Moysich, K B Edwards, R Jennison, E Kjaer, S K Hogdall, E Hogdall, C K Goode, E L Sellers, T A Vierkant, R A Cunningham, J C Schildkraut, J M Berchuck, A Moorman, P G Iversen, E S Cramer, D W Terry, K L Vitonis, A F Titus-Ernstoff, L Song, H Pharoah, P D P Spurdle, A B Anton-Culver, H Ziogas, A Brewster, W Galitovskiy, V Chenevix-Trench, G |
| author_facet | Pearce, C L Near, A M Van Den Berg, D J Ramus, S J Gentry-Maharaj, A Menon, U Gayther, S A Anderson, A R Edlund, C K Wu, A H Chen, X Beesley, J Webb, P M Holt, S K Chen, C Doherty, J A Rossing, M A Whittemore, A S McGuire, V DiCioccio, R A Goodman, M T Lurie, G Carney, M E Wilkens, L R Ness, R B Moysich, K B Edwards, R Jennison, E Kjaer, S K Hogdall, E Hogdall, C K Goode, E L Sellers, T A Vierkant, R A Cunningham, J C Schildkraut, J M Berchuck, A Moorman, P G Iversen, E S Cramer, D W Terry, K L Vitonis, A F Titus-Ernstoff, L Song, H Pharoah, P D P Spurdle, A B Anton-Culver, H Ziogas, A Brewster, W Galitovskiy, V Chenevix-Trench, G |
| author_sort | Pearce, C L |
| collection | PubMed |
| description | The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P⩽0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20–6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted. |
| format | Text |
| id | pubmed-2634713 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2009 |
| publisher | Nature Publishing Group |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-26347132010-01-27 Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium Pearce, C L Near, A M Van Den Berg, D J Ramus, S J Gentry-Maharaj, A Menon, U Gayther, S A Anderson, A R Edlund, C K Wu, A H Chen, X Beesley, J Webb, P M Holt, S K Chen, C Doherty, J A Rossing, M A Whittemore, A S McGuire, V DiCioccio, R A Goodman, M T Lurie, G Carney, M E Wilkens, L R Ness, R B Moysich, K B Edwards, R Jennison, E Kjaer, S K Hogdall, E Hogdall, C K Goode, E L Sellers, T A Vierkant, R A Cunningham, J C Schildkraut, J M Berchuck, A Moorman, P G Iversen, E S Cramer, D W Terry, K L Vitonis, A F Titus-Ernstoff, L Song, H Pharoah, P D P Spurdle, A B Anton-Culver, H Ziogas, A Brewster, W Galitovskiy, V Chenevix-Trench, G Br J Cancer Genetics and Genomics The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P⩽0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20–6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted. Nature Publishing Group 2009-01-27 2009-01-06 /pmc/articles/PMC2634713/ /pubmed/19127255 http://dx.doi.org/10.1038/sj.bjc.6604820 Text en Copyright © 2009 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Genetics and Genomics Pearce, C L Near, A M Van Den Berg, D J Ramus, S J Gentry-Maharaj, A Menon, U Gayther, S A Anderson, A R Edlund, C K Wu, A H Chen, X Beesley, J Webb, P M Holt, S K Chen, C Doherty, J A Rossing, M A Whittemore, A S McGuire, V DiCioccio, R A Goodman, M T Lurie, G Carney, M E Wilkens, L R Ness, R B Moysich, K B Edwards, R Jennison, E Kjaer, S K Hogdall, E Hogdall, C K Goode, E L Sellers, T A Vierkant, R A Cunningham, J C Schildkraut, J M Berchuck, A Moorman, P G Iversen, E S Cramer, D W Terry, K L Vitonis, A F Titus-Ernstoff, L Song, H Pharoah, P D P Spurdle, A B Anton-Culver, H Ziogas, A Brewster, W Galitovskiy, V Chenevix-Trench, G Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium |
| title | Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium |
| title_full | Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium |
| title_fullStr | Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium |
| title_full_unstemmed | Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium |
| title_short | Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium |
| title_sort | validating genetic risk associations for ovarian cancer through the international ovarian cancer association consortium |
| topic | Genetics and Genomics |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634713/ https://www.ncbi.nlm.nih.gov/pubmed/19127255 http://dx.doi.org/10.1038/sj.bjc.6604820 |
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