Genetic variation in TYMS in the one-carbon transfer pathway is associated with ovarian carcinoma types in the Ovarian Cancer Association Consortium

Linda E Kelemen; Marc T Goodman; Valerie McGuire; Mary Anne Rossing; Penelope M Webb; Martin Köbel; Hoda Anton-Culver; Jonathan Beesley; Andrew Berchuck; Sony Brar; Michael E Carney; Jenny Chang-Claude; Georgia Chenevix-Trench; Daniel W Cramer; Julie M Cunningham; Richard A Dicioccio; Jennifer A Doherty; Douglas F Easton; Zachary S Fredericksen; Brooke L Fridley; Margaret A Gates; Simon A Gayther; Aleksandra Gentry-Maharaj; Estrid Høgdall; Susanne Krüger Kjaer; Galina Lurie; Usha Menon; Patricia G Moorman; Kirsten Moysich; Roberta B Ness; Rachel T Palmieri; Celeste L Pearce; Paul D P Pharoah; Susan J Ramus; Honglin Song; Daniel O Stram; Shelley S Tworoger; David Van Den Berg; Robert A Vierkant; Shan Wang-Gohrke; Alice S Whittemore; Lynne R Wilkens; Anna H Wu; Joellen M Schildkraut; Thomas A Sellers; Ellen L Goode; Australian Cancer Study (Ovarian Cancer) Study Group

doi:http://dx.doi.org/10.1158/1055-9965.EPI-09-1317

Genetic variation in TYMS in the one-carbon transfer pathway is associated with ovarian carcinoma types in the Ovarian Cancer Association Consortium

Linda E Kelemen, Marc T Goodman, Valerie McGuire, Mary Anne Rossing, Penelope M Webb, Martin Köbel, Hoda Anton-Culver, Jonathan Beesley, Andrew Berchuck, Sony Brar, Michael E Carney, Jenny Chang-Claude, Georgia Chenevix-Trench, Daniel W Cramer, Julie M Cunningham, Richard A Dicioccio, Jennifer A Doherty, Douglas F Easton, Zachary S Fredericksen, Brooke L FridleyMargaret A Gates, Simon A Gayther, Aleksandra Gentry-Maharaj, Estrid Høgdall, Susanne Krüger Kjaer, Galina Lurie, Usha Menon, Patricia G Moorman, Kirsten Moysich, Roberta B Ness, Rachel T Palmieri, Celeste L Pearce, Paul D P Pharoah, Susan J Ramus, Honglin Song, Daniel O Stram, Shelley S Tworoger, David Van Den Berg, Robert A Vierkant, Shan Wang-Gohrke, Alice S Whittemore, Lynne R Wilkens, Anna H Wu, Joellen M Schildkraut, Thomas A Sellers, Ellen L Goode, Australian Cancer Study (Ovarian Cancer) Study Group

21 Citations (Scopus)

Abstract

Background: We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample of assembled cases to investigate associations by histologic type. Methods: Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and study site. Results: The five polymorphisms were not associated with ovarian carcinoma overall (P _trend > 0.13); however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; P _{heterogeneity} = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05). Conclusions: TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification. Impact: Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology.

Original language	English
Journal	Cancer Epidemiology, Biomarkers & Prevention
Volume	19
Issue number	7
Pages (from-to)	1822-30
Number of pages	9
ISSN	1055-9965
DOIs	https://doi.org/10.1158/1055-9965.EPI-09-1317
Publication status	Published - 1 Jul 2010

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Kelemen, L. E., Goodman, M. T., McGuire, V., Rossing, M. A., Webb, P. M., Köbel, M., Anton-Culver, H., Beesley, J., Berchuck, A., Brar, S., Carney, M. E., Chang-Claude, J., Chenevix-Trench, G., Cramer, D. W., Cunningham, J. M., Dicioccio, R. A., Doherty, J. A., Easton, D. F., Fredericksen, Z. S., ... Australian Cancer Study (Ovarian Cancer) Study Group (2010). Genetic variation in TYMS in the one-carbon transfer pathway is associated with ovarian carcinoma types in the Ovarian Cancer Association Consortium. Cancer Epidemiology, Biomarkers & Prevention, 19(7), 1822-30. https://doi.org/10.1158/1055-9965.EPI-09-1317

Genetic variation in TYMS in the one-carbon transfer pathway is associated with ovarian carcinoma types in the Ovarian Cancer Association Consortium. / Kelemen, Linda E; Goodman, Marc T; McGuire, Valerie et al.

In: Cancer Epidemiology, Biomarkers & Prevention, Vol. 19, No. 7, 01.07.2010, p. 1822-30.

Research output: Contribution to journal › Journal article › Research › peer-review

Kelemen, LE, Goodman, MT, McGuire, V, Rossing, MA, Webb, PM, Köbel, M, Anton-Culver, H, Beesley, J, Berchuck, A, Brar, S, Carney, ME, Chang-Claude, J, Chenevix-Trench, G, Cramer, DW, Cunningham, JM, Dicioccio, RA, Doherty, JA, Easton, DF, Fredericksen, ZS, Fridley, BL, Gates, MA, Gayther, SA, Gentry-Maharaj, A, Høgdall, E, Kjaer, SK, Lurie, G, Menon, U, Moorman, PG, Moysich, K, Ness, RB, Palmieri, RT, Pearce, CL, Pharoah, PDP, Ramus, SJ, Song, H, Stram, DO, Tworoger, SS, Van Den Berg, D, Vierkant, RA, Wang-Gohrke, S, Whittemore, AS, Wilkens, LR, Wu, AH, Schildkraut, JM, Sellers, TA, Goode, EL & Australian Cancer Study (Ovarian Cancer) Study Group 2010, 'Genetic variation in TYMS in the one-carbon transfer pathway is associated with ovarian carcinoma types in the Ovarian Cancer Association Consortium', Cancer Epidemiology, Biomarkers & Prevention, vol. 19, no. 7, pp. 1822-30. https://doi.org/10.1158/1055-9965.EPI-09-1317

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title = "Genetic variation in TYMS in the one-carbon transfer pathway is associated with ovarian carcinoma types in the Ovarian Cancer Association Consortium",

abstract = "Background: We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample of assembled cases to investigate associations by histologic type. Methods: Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and study site. Results: The five polymorphisms were not associated with ovarian carcinoma overall (P trend > 0.13); however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; P heterogeneity = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05). Conclusions: TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification. Impact: Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology.",

author = "Kelemen, {Linda E} and Goodman, {Marc T} and Valerie McGuire and Rossing, {Mary Anne} and Webb, {Penelope M} and Martin K{\"o}bel and Hoda Anton-Culver and Jonathan Beesley and Andrew Berchuck and Sony Brar and Carney, {Michael E} and Jenny Chang-Claude and Georgia Chenevix-Trench and Cramer, {Daniel W} and Cunningham, {Julie M} and Dicioccio, {Richard A} and Doherty, {Jennifer A} and Easton, {Douglas F} and Fredericksen, {Zachary S} and Fridley, {Brooke L} and Gates, {Margaret A} and Gayther, {Simon A} and Aleksandra Gentry-Maharaj and Estrid H{\o}gdall and Kjaer, {Susanne Kr{\"u}ger} and Galina Lurie and Usha Menon and Moorman, {Patricia G} and Kirsten Moysich and Ness, {Roberta B} and Palmieri, {Rachel T} and Pearce, {Celeste L} and Pharoah, {Paul D P} and Ramus, {Susan J} and Honglin Song and Stram, {Daniel O} and Tworoger, {Shelley S} and {Van Den Berg}, David and Vierkant, {Robert A} and Shan Wang-Gohrke and Whittemore, {Alice S} and Wilkens, {Lynne R} and Wu, {Anna H} and Schildkraut, {Joellen M} and Sellers, {Thomas A} and Goode, {Ellen L} and H{\o}gdall, {Estrid Vilma Solyom}",

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doi = "http://dx.doi.org/10.1158/1055-9965.EPI-09-1317",

language = "English",

volume = "19",

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TY - JOUR

T1 - Genetic variation in TYMS in the one-carbon transfer pathway is associated with ovarian carcinoma types in the Ovarian Cancer Association Consortium

AU - Kelemen, Linda E

AU - Goodman, Marc T

AU - McGuire, Valerie

AU - Rossing, Mary Anne

AU - Webb, Penelope M

AU - Köbel, Martin

AU - Anton-Culver, Hoda

AU - Beesley, Jonathan

AU - Berchuck, Andrew

AU - Brar, Sony

AU - Carney, Michael E

AU - Chang-Claude, Jenny

AU - Chenevix-Trench, Georgia

AU - Cramer, Daniel W

AU - Cunningham, Julie M

AU - Dicioccio, Richard A

AU - Doherty, Jennifer A

AU - Easton, Douglas F

AU - Fredericksen, Zachary S

AU - Fridley, Brooke L

AU - Gates, Margaret A

AU - Gayther, Simon A

AU - Gentry-Maharaj, Aleksandra

AU - Høgdall, Estrid

AU - Kjaer, Susanne Krüger

AU - Lurie, Galina

AU - Menon, Usha

AU - Moorman, Patricia G

AU - Moysich, Kirsten

AU - Ness, Roberta B

AU - Palmieri, Rachel T

AU - Pearce, Celeste L

AU - Pharoah, Paul D P

AU - Ramus, Susan J

AU - Song, Honglin

AU - Stram, Daniel O

AU - Tworoger, Shelley S

AU - Van Den Berg, David

AU - Vierkant, Robert A

AU - Wang-Gohrke, Shan

AU - Whittemore, Alice S

AU - Wilkens, Lynne R

AU - Wu, Anna H

AU - Schildkraut, Joellen M

AU - Sellers, Thomas A

AU - Goode, Ellen L

AU - Australian Cancer Study (Ovarian Cancer) Study Group

PY - 2010/7/1

Y1 - 2010/7/1

N2 - Background: We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample of assembled cases to investigate associations by histologic type. Methods: Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and study site. Results: The five polymorphisms were not associated with ovarian carcinoma overall (P trend > 0.13); however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; P heterogeneity = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05). Conclusions: TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification. Impact: Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology.

AB - Background: We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample of assembled cases to investigate associations by histologic type. Methods: Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and study site. Results: The five polymorphisms were not associated with ovarian carcinoma overall (P trend > 0.13); however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; P heterogeneity = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05). Conclusions: TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification. Impact: Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology.

U2 - http://dx.doi.org/10.1158/1055-9965.EPI-09-1317

DO - http://dx.doi.org/10.1158/1055-9965.EPI-09-1317

M3 - Journal article

SN - 1055-9965

VL - 19

SP - 1822

EP - 1830

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

IS - 7

ER -

Genetic variation in TYMS in the one-carbon transfer pathway is associated with ovarian carcinoma types in the Ovarian Cancer Association Consortium

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