Abstract
Background: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. Methods: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. Results: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66×10-4). Conclusion: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.
| Original language | English |
|---|---|
| Article number | e0128106 |
| Number of pages | 17 |
| Journal | PLoS ONE |
| Volume | 10 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 19 Jun 2015 |
| Externally published | Yes |
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Common genetic variation in cellular transport genes and epithelial ovarian cancer (EOC) risk. / Chornokur, Ganna; Lin, Hui-Yi Lin; Tyrer, Jonathan P.; Lawrenson, Kate; Dennis, Joe; Amankwah, Ernest K.; Qu, Xiaotao; Tsai, Ya-Yu; Jim, Heather S.L.; Chen, Zhihua; Chen, Y. Ann; Permuth-Wey, Jennifer; Aben, Katja K.H.; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V.; Bean, Yukie Tarumi; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bunker, Clareann H; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer Anne; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F; Eccles, Diana M; Edwards, Robert P.; Ekici, Arif B; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind M; Goodman, Marc T; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Claus K.; Hogdall, Estrid; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Ji, Bu-tian; Karlan, Beth Y.; Kelemen, Linda E.; Kellar, Mellissa; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne Krüger; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Iain A; Menon, Usha N; Milne, Roger L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Pike, Malcolm C; Poole, Elizabeth M; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga Birgitte; Schernhammer, Eva S; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Sucheston, Lara E; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Thomsen, Lotte; Tangen, Ingvild L; Tworoger, Shelley S; Altena, Anne Mvan; Vierkant, Robert A; Vergote, Ignace; Walsh, Christine S; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R.; Wu, Anna H; Wu, Xifeng; Woo, Yin Ling; Yang, Hannah P; Zheng, Wei; Ziogas, Argyrios; Hasmad, Hanis Nazihah; Berchuck, Andrew; Chenevix-Trench, Georgia; Iversen, Edwin S.; Schildkraut, Joellen M; Ramus, Susan J; Goode, Ellen L; Monteiro, Alvaro N.A.; Gayther, Simon A; Narod, Steven A; Pharoah, Paul D P; Sellers, Thomas A; Phelan, Catherine M.
In: PLoS ONE, Vol. 10, No. 6, e0128106, 19.06.2015.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Common genetic variation in cellular transport genes and epithelial ovarian cancer (EOC) risk
AU - Chornokur, Ganna
AU - Lin, Hui-Yi Lin
AU - Tyrer, Jonathan P.
AU - Lawrenson, Kate
AU - Dennis, Joe
AU - Amankwah, Ernest K.
AU - Qu, Xiaotao
AU - Tsai, Ya-Yu
AU - Jim, Heather S.L.
AU - Chen, Zhihua
AU - Chen, Y. Ann
AU - Permuth-Wey, Jennifer
AU - Aben, Katja K.H.
AU - Anton-Culver, Hoda
AU - Antonenkova, Natalia
AU - Bruinsma, Fiona
AU - Bandera, Elisa V.
AU - Bean, Yukie Tarumi
AU - Beckmann, Matthias W.
AU - Bisogna, Maria
AU - Bjorge, Line
AU - Bogdanova, Natalia
AU - Brinton, Louise A.
AU - Brooks-Wilson, Angela
AU - Bunker, Clareann H
AU - Butzow, Ralf
AU - Campbell, Ian G.
AU - Carty, Karen
AU - Chang-Claude, Jenny
AU - Cook, Linda S.
AU - Cramer, Daniel W.
AU - Cunningham, Julie M.
AU - Cybulski, Cezary
AU - Dansonka-Mieszkowska, Agnieszka
AU - Du Bois, Andreas
AU - Despierre, Evelyn
AU - Dicks, Ed
AU - Doherty, Jennifer Anne
AU - Dörk, Thilo
AU - Dürst, Matthias
AU - Easton, Douglas F
AU - Eccles, Diana M
AU - Edwards, Robert P.
AU - Ekici, Arif B
AU - Fasching, Peter A.
AU - Fridley, Brooke L.
AU - Gao, Yu-Tang
AU - Gentry-Maharaj, Aleksandra
AU - Giles, Graham G.
AU - Glasspool, Rosalind M
AU - Goodman, Marc T
AU - Gronwald, Jacek
AU - Harrington, Patricia
AU - Harter, Philipp
AU - Hein, Alexander
AU - Heitz, Florian
AU - Hildebrandt, Michelle A T
AU - Hillemanns, Peter
AU - Hogdall, Claus K.
AU - Hogdall, Estrid
AU - Hosono, Satoyo
AU - Jakubowska, Anna
AU - Jensen, Allan
AU - Ji, Bu-tian
AU - Karlan, Beth Y.
AU - Kelemen, Linda E.
AU - Kellar, Mellissa
AU - Kiemeney, Lambertus A.
AU - Krakstad, Camilla
AU - Kjaer, Susanne Krüger
AU - Kupryjanczyk, Jolanta
AU - Lambrechts, Diether
AU - Lambrechts, Sandrina
AU - Le, Nhu D.
AU - Lee, Alice W
AU - Lele, Shashi
AU - Leminen, Arto
AU - Lester, Jenny
AU - Levine, Douglas A.
AU - Liang, Dong
AU - Lim, Boon Kiong
AU - Lissowska, Jolanta
AU - Lu, Karen
AU - Lubinski, Jan
AU - Lundvall, Lene
AU - Massuger, Leon F A G
AU - Matsuo, Keitaro
AU - McGuire, Valerie
AU - McLaughlin, John R
AU - McNeish, Iain A
AU - Menon, Usha N
AU - Milne, Roger L
AU - Modugno, Francesmary
AU - Moysich, Kirsten B
AU - Ness, Roberta B
AU - Nevanlinna, Heli
AU - Eilber, Ursula
AU - Odunsi, Kunle
AU - Olson, Sara H
AU - Orlow, Irene
AU - Orsulic, Sandra
AU - Weber, Rachel Palmieri
AU - Paul, James
AU - Pearce, Celeste L
AU - Pejovic, Tanja
AU - Pelttari, Liisa M
AU - Pike, Malcolm C
AU - Poole, Elizabeth M
AU - Risch, Harvey A
AU - Rosen, Barry
AU - Rossing, Mary Anne
AU - Rothstein, Joseph H
AU - Rudolph, Anja
AU - Runnebaum, Ingo B
AU - Rzepecka, Iwona K
AU - Salvesen, Helga Birgitte
AU - Schernhammer, Eva S
AU - Schwaab, Ira
AU - Shu, Xiao-Ou
AU - Shvetsov, Yurii B
AU - Siddiqui, Nadeem
AU - Sieh, Weiva
AU - Song, Honglin
AU - Southey, Melissa C.
AU - Spiewankiewicz, Beata
AU - Sucheston, Lara E
AU - Teo, Soo-Hwang
AU - Terry, Kathryn L
AU - Thompson, Pamela J
AU - Thomsen, Lotte
AU - Tangen, Ingvild L
AU - Tworoger, Shelley S
AU - Altena, Anne Mvan
AU - Vierkant, Robert A
AU - Vergote, Ignace
AU - Walsh, Christine S
AU - Wang-Gohrke, Shan
AU - Wentzensen, Nicolas
AU - Whittemore, Alice S
AU - Wicklund, Kristine G
AU - Wilkens, Lynne R.
AU - Wu, Anna H
AU - Wu, Xifeng
AU - Woo, Yin Ling
AU - Yang, Hannah P
AU - Zheng, Wei
AU - Ziogas, Argyrios
AU - Hasmad, Hanis Nazihah
AU - Berchuck, Andrew
AU - Chenevix-Trench, Georgia
AU - Iversen, Edwin S.
AU - Schildkraut, Joellen M
AU - Ramus, Susan J
AU - Goode, Ellen L
AU - Monteiro, Alvaro N.A.
AU - Gayther, Simon A
AU - Narod, Steven A
AU - Pharoah, Paul D P
AU - Sellers, Thomas A
AU - Phelan, Catherine M
PY - 2015/6/19
Y1 - 2015/6/19
N2 - Background: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. Methods: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. Results: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66×10-4). Conclusion: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.
AB - Background: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. Methods: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. Results: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66×10-4). Conclusion: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.
UR - http://www.scopus.com/inward/record.url?scp=84939197812&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0128106
DO - 10.1371/journal.pone.0128106
M3 - Article
C2 - 26091520
AN - SCOPUS:84939197812
VL - 10
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 6
M1 - e0128106
ER -