Citations 2
Consortium analysis of gene and gene–folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk
Kelemen, Linda E. , Terry, Kathryn L. , Goodman, Marc T. , Webb, Penelope M. , McGuire, Valerie , Rossing, Mary Anne, Wang, Qinggang , Dicks, Ed , Song, Honglin , Kupryjańczyk, Jolanta , Dansonka‐Mieszkowska, Agnieszka , Plisiecka-Hałasa, Joanna, Timorek, Agnieszka, Menon, Usha , Gayther, Simon A. , Ramus, Susan J. , Narod, Steven A., McLaughlin, John R., Glasspool, Rosalind , Lubiński, Jan , Jakubowska, Anna , Kiemeney, Lambertus A. , Massuger, Leon F.A.G. , Altena, Anne M. van , Aben, Katja K.H. , Olson, Sara H. , Orlow, Irene , Levine, Douglas A. , Bisogna, Maria, Southey, Melissa C. , Bruinsma, Fiona , Kjær, Susanne K. , Høgdall, Estrid , Jensen, Allan , Høgdall, Claus , Lundvall, Lene, Engelholm, Svend‐Aage, Harter, Philipp , Schwaab, Ira, Nevanlinna, Heli , Pelttari, Liisa M. , Leminen, Arto, Thompson, Pamela J., Lurie, Galina, Lambrechts, Diether , Nieuwenhuysen, Els Van , Lambrechts, Sandrina, Vergote, Ignace , Beesley, Jonathan, Investigators, AOCS Study Group/ACS, Fasching, Peter A. , Beckmann, Matthias W. , Hein, Alexander , Ekici, Arif B. , Wu, Anna H. , Pearce, Celeste Leigh, Pike, Malcolm C., Chang‐Claude, Jenny , Dörk, Thilo , Hillemanns, Peter , Runnebaum, Ingo B. , Bogdanova, Natalia , Antonenkova, Natalia, Odunsi, Kunle , Edwards, Robert P., Kelley, Joseph L., Ness, Roberta B., Walsh, Christine , Lester, Jenny, Oršulić, Sandra , Vierkant, Robert A. , Cunningham, Julie M. , Wu, Xifeng , Lu, Karen H., Hildebrandt, Michelle A.T., Weber, Rachel Palmieri , Iversen, Edwin S., Tworoger, Shelley S. , Salvesen, Helga B., Tangen, Ingvild L. , Bean, Yukie T., Kellar, Melissa, Wentzensen, Nicolas , Brinton, Louise A. , Lissowska, Jolanta , García‐Closas, Montserrat , Campbell, Ian , Eccles, Diana , Whittemore, Alice S. , Sieh, Weiva , Rothstein, Joseph H. , Phelan, Catherine M., Moysich, Kirsten B., Goode, Ellen L. , Schildkraut, Joellen M. , Sellers, Thomas A. , Le, Nhu D. , Lu, Karen H. , Zheng, Wei , Lambrechts, Diether , Bandera, Elisa V. , Tyrer, Jonathan P. , Gentry‐Maharaj, Aleksandra , Risch, Harvey A. , McLaughlin, John R., Siddiqui, Nadeem , Paul, James , Carty, Karen , Gronwald, Jacek , Cybulski, Cezary , Cramer, Daniel W. , Giles, Graham G. , Heitz, Florian , Bois, Andreas du , Bützow, Ralf C. , Wilkens, Lynne R. , Beesley, Jonathan, Investigators, AOCS Study Group/ACS, Doherty, Jennifer A. , Stram, Daniel O. , Rudolph, Anja , Dürst, Matthias , Modugno, Francesmary , Karlan, Beth Y. , Fridley, Brooke L. , Liang, Dong , Hildebrandt, Michelle A.T. , Poole, Elizabeth M. , Krakstad, Camilla , Bjørge, Line , Pejovic, Tanja B. , Anton‐Culver, Hoda , Ziogas, Argyrios , Berchuck, Andrew , Pharoah, Paul D.P. , Brooks‐Wilson, Angela , Cook, Linda S. , Pelttari, L M , Nevanlinna, H , Dörk, Thilo , Lambrechts, Diether , Kiemeney, Lambertus A , Kjaer, Susanne K , Ramus, Susan J , Tworoger, Shelley S , Webb, Penelope M , Hein, Alexander , Hillemanns, Peter , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Moysich, Kirsten , Orlow, Irene , Lissowska, Jolanta , Campbell, Ian G , Southey, Melissa C , Glasspool, Rosalind , Jakubowska, Anna , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , García-Closas, Montserrat , Ekici, Arif B , Bogdanova, Natalia V , Zheng, Wei , Høgdall, Estrid , Høgdall, Claus K , Lubinski, Jan , Goodman, Marc T
Molecular Nutrition & Food Research | July 28, 2014 | Volume: 58 | Issue: 10 | Pages: 2023-2035
ScopeWe reevaluated previously reported associations between variants in pathways of one‐carbon (1‐C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake.Methods and resultsOdds ratios (OR) for 446 genetic variants were estimated among 13 410 OC cases and 22 635 controls, and among 2281 cases and 3444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for dihydropyrimidine dehydrogenase (DPYD) variants rs11587873 (OR = 0.92; p = 6 × 10−5) and rs828054 (OR = 1.06; p = 1 × 10−4). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with folate in a multivariant analysis (corrected p = 9.9 × 10−6) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in 1‐C transfer, previously reported with OC, suggested lower risk at higher folate (pinteraction = 0.03–0.006).ConclusionVariation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP‐by‐folate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC.
Abstract 2854: Genetic variation in stromal genes decorin and lumican and susceptibility to serous ovarian cancer
Amankwah, Ernest K. , Wang, Qinggang , Beesley, Jonathan, Johnatty, Sharon E. , Phelan, Catherine M., Cunningham, Julie M. , Vachon, Celine M. , Iversen, Edwin S., Schildkraut, Joellen M. , Goode, Ellen L. , Sellers, Thomas A. , Kelemen, Linda E. , Tsai, Ya-Yu , Fridley, Brooke L. , Webb, Penelope M. , Chenevix‐Trench, Georgia , Vachon, Celine M. , Vierkant, Robert A. , Berchuck, Andrew
Cancer Research | February 25, 2011 | Volume: 70 | Issue: 8_Supplement | Pages: 2854-2854
Abstract Introduction: Alterations in components of the stromal tissue that underlie the epithelium can initiate, promote or inhibit epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) are stromal genes with reduced expression in serous ovarian cancer. We hypothesized that single nucleotide polymorphisms (SNPs) in these genes may influence susceptibility to serous ovarian cancer. Methods: To test this hypothesis, we compared genotype frequencies of 11 tagSNPs in DCN and LUM between 397 Caucasian cases with primary serous ovarian cancer and 920 Caucasian controls in two studies conducted at Mayo Clinic and Duke University (discovery set). Associations were evaluated further in a third Caucasian population of 436 cases and 1,098 controls in Australia (replication set). TagSNPs were selected from unrelated Caucasian samples within HapMap based on the following criteria: (i) minor allele frequency ≥ 0.05, (ii) pairwise linkage disequilibrium (LD) of r2 ≥ 0.8, and (iii) location within, and 5kb upstream and downstream of, each gene region. Genotyping was performed using the Illumina GoldenGate™ assay and associations between SNPs and serous cancer were evaluated using unconditional logistic regression to estimate per allele odds ratios (OR) and 95% confidence intervals (95%CI). Untyped genotypes for DCN rs13312816 in the discovery set, and for DCN rs3138165 and LUM rs17018765 in the replication set, were imputed using the MACH software. Results: In the discovery set, we observed inverse associations between DCN rs3138165 (OR=0.7; 95%CI=0.5-1.0), DCN rs13312816 (OR=0.7; 95%CI=0.5-1.0), DCN rs516115 (OR=0.8; 95%CI=0.7-1.0) and LUM rs17018765 (OR=0.7; 95%CI=0.5-1.0) and risk of serous ovarian cancers (all Ptrend=0.06). Associations were confirmed in the replication set for DCN rs3138165 (OR=0.6; 95%CI=0.4-0.9; Ptrend=0.009), DCN rs13312816 (OR=0.7; 95%CI=0.5-0.9; Ptrend=0.01) and LUM rs17018765 (OR=0.6; 95%CI=0.4-0.9; Ptrend=0.008), but not for DCN rs516115 (Ptrend=0.20). To increase statistical power, data from the discovery and replication sets were combined (833 cases and 2,013 controls) following confirmation of no statistical heterogeneity in the ORs between study sites. In the combined sample, associations were strengthened for DCN rs3138165 (OR=0.7; 95%CI=0.5-0.9; Ptrend=0.002), DCN rs13312816 (OR=0.7; 95%CI=0.5-0.9; Ptrend=0.002), DCN rs516115 (OR=0.9; 95%CI=0.8-1.0; Ptrend=0.03) and LUM rs17018765 (OR=0.6; 95%CI=0.5-0.8; Ptrend=0.001). All four SNPs were in the same LD block on chromosome 12, suggesting that serous ovarian cancer susceptibility may be driven by a single, correlated variant in the region. Conclusion: The findings of this study suggest that genetic variation in DCN and LUM may influence susceptibility to serous ovarian cancer and contribute to the mounting evidence that supports the role of the stroma in epithelial ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2854.