Citations 12
Risk of Ovarian Cancer and the NF-κB Pathway: Genetic Association with IL1A and TNFSF10
Charbonneau, Bridget, Block, Matthew S., Bamlet, William R., Vierkant, Robert A., Kalli, Kimberly R., Fogarty, Zachary, Rider, David N., Sellers, Thomas A., Tworoger, Shelley S., Poole, Elizabeth, Risch, Harvey A., Salvesen, Helga B., Kiemeney, Lambertus A., Baglietto, Laura, Giles, Graham G., Severi, Gianluca, Trabert, Britton, Wentzensen, Nicolas, Chenevix-Trench, Georgia, group, for AOCS/ACS, Whittemore, Alice S., Sieh, Weiva, Chang-Claude, Jenny, Bandera, Elisa V., Orlow, Irene, Terry, Kathryn, Goodman, Marc T., Thompson, Pamela J., Cook, Linda S., Rossing, Mary Anne, Ness, Roberta B., Narod, Steven A., Kupryjanczyk, Jolanta, Lu, Karen, Butzow, Ralf, Dörk, Thilo, Pejovic, Tanja, Campbell, Ian, Le, Nhu D., Bunker, Clareann H., Bogdanova, Natalia, Runnebaum, Ingo B., Eccles, Diana, Paul, James, Wu, Anna H., Gayther, Simon A., Hogdall, Estrid, Heitz, Florian, Kaye, Stanley B., Karlan, Beth Y., Anton-Culver, Hoda, Gronwald, Jacek, Hogdall, Claus K., Lambrechts, Diether, Fasching, Peter A., Menon, Usha, Schildkraut, Joellen, Pearce, Celeste Leigh, Levine, Douglas A., Kjaer, Susanne Kruger, Cramer, Daniel, Flanagan, James M., Phelan, Catherine M., Brown, Robert, Massuger, Leon F.A.G., Song, Honglin, Doherty, Jennifer A., Krakstad, Camilla, Liang, Dong, Odunsi, Kunle, Berchuck, Andrew, Jensen, Allan, Lubiński, Jan, Nevanlinna, Heli, Bean, Yukie T., Lurie, Galina, Ziogas, Argyrios, Walsh, Christine, Despierre, Evelyn, Brinton, Louise, Hein, Alexander, Rudolph, Anja, Dansonka-Mieszkowska, Agnieszka, Olson, Sara H., Harter, Philipp, Tyrer, Jonathan, Vitonis, Allison F., Brooks-Wilson, Angela, Aben, Katja K., Pike, Malcolm C., Ramus, Susan J., Wik, Elisabeth, Cybulski, Cezary, Lin, Jie, Sucheston, Lara, Edwards, Robert, McGuire, Valerie, Lester, Jenny, Bois, Andreas du, Lundvall, Lene, Wang-Gohrke, Shan, Szafron, Lukasz M., Lambrechts, Sandrina, Yang, Hannah, Beckmann, Matthias W., Pelttari, Liisa M., Altena, Anne M. Van, Berg, David van den, Halle, Mari K., Gentry-Maharaj, Aleksandra, Schwaab, Ira, Chandran, Urmila, Menkiszak, Janusz, Ekici, Arif B., Wilkens, Lynne R., Leminen, Arto, Modugno, Francesmary, Friel, Grace, Rothstein, Joseph H., Vergote, Ignace, Garcia-Closas, Montserrat, Hildebrandt, Michelle A.T., Sobiczewski, Piotr, Kelemen, Linda E., Pharoah, Paul D.P., Moysich, Kirsten, Knutson, Keith L., Cunningham, Julie M., Fridley, Brooke L., Goode, Ellen L., Vierkant, Robert A. , Bamlet, William R. , Lu, Karen H. , Ramus, Susan J. , Kjær, Susanne K. , Høgdall, Estrid , Høgdall, Claus , Goodman, Marc T. , García‐Closas, Montserrat , Chenevix‐Trench, Georgia , Lubiński, Jan , Nevanlinna, Heli , Olson, Sara H. , Dörk, Thilo , Giles, Graham G. , Severi, Gianluca , Menon, Usha , Terry, Kathryn L. , Tworoger, Shelley S. , Baglietto, Laura , Bogdanova, Natalia , Ekici, Arif B. , Orlow, Irene , Eccles, Diana , Hein, Alexander , Lambrechts, Diether , Jensen, Allan , Brown, Robert , Bandera, Elisa V. , Campbell, Ian , Kiemeney, Lambertus A. , Aben, Katja K.H. , Sieh, Weiva , Fogarty, Zachary C. , Levine, Douglas A. , Kupryjańczyk, Jolanta , Heitz, Florian , Flanagan, James M. , Dansonka‐Mieszkowska, Agnieszka , Menkiszak, Janusz , Pelttari, Liisa M. , Krakstad, Camilla , Trabert, Britton , Sobiczewski, Piotr , Lambrechts, Diether , Szafron, Lukasz M. , Charbonneau, Bridget, Block, Matthew S., Bamlet, William R., Vierkant, Robert A., Kalli, Kimberly R., Fogarty, Zachary, Rider, David N., Sellers, Thomas A., Tworoger, Shelley S., Poole, Elizabeth, Risch, Harvey A., Salvesen, Helga B., Kiemeney, Lambertus A., Baglietto, Laura, Giles, Graham G., Severi, Gianluca, Trabert, Britton, Wentzensen, Nicolas, Chenevix-Trench, Georgia, group, for AOCS/ACS, Whittemore, Alice S., Sieh, Weiva, Chang-Claude, Jenny, Bandera, Elisa V., Orlow, Irene, Terry, Kathryn, Goodman, Marc T., Thompson, Pamela J., Cook, Linda S., Rossing, Mary Anne, Ness, Roberta B., Narod, Steven A., Kupryjanczyk, Jolanta, Lu, Karen, Butzow, Ralf, Dörk, Thilo, Pejovic, Tanja, Campbell, Ian, Le, Nhu D., Bunker, Clareann H., Bogdanova, Natalia, Runnebaum, Ingo B., Eccles, Diana, Paul, James, Wu, Anna H., Gayther, Simon A., Hogdall, Estrid, Heitz, Florian, Kaye, Stanley B., Karlan, Beth Y., Anton-Culver, Hoda, Gronwald, Jacek, Hogdall, Claus K., Lambrechts, Diether, Fasching, Peter A., Menon, Usha, Schildkraut, Joellen, Pearce, Celeste Leigh, Levine, Douglas A., Kjaer, Susanne Kruger, Cramer, Daniel, Flanagan, James M., Phelan, Catherine M., Brown, Robert, Massuger, Leon F.A.G., Song, Honglin, Doherty, Jennifer A., Krakstad, Camilla, Liang, Dong, Odunsi, Kunle, Berchuck, Andrew, Jensen, Allan, Lubiński, Jan, Nevanlinna, Heli, Bean, Yukie T., Lurie, Galina, Ziogas, Argyrios, Walsh, Christine, Despierre, Evelyn, Brinton, Louise, Hein, Alexander, Rudolph, Anja, Dansonka-Mieszkowska, Agnieszka, Olson, Sara H., Harter, Philipp, Tyrer, Jonathan, Vitonis, Allison F., Brooks-Wilson, Angela, Aben, Katja K., Pike, Malcolm C., Ramus, Susan J., Wik, Elisabeth, Cybulski, Cezary, Lin, Jie, Sucheston, Lara, Edwards, Robert, McGuire, Valerie, Lester, Jenny, Bois, Andreas du, Lundvall, Lene, Wang-Gohrke, Shan, Szafron, Lukasz M., Lambrechts, Sandrina, Yang, Hannah, Beckmann, Matthias W., Pelttari, Liisa M., Altena, Anne M. Van, Berg, David van den, Halle, Mari K., Gentry-Maharaj, Aleksandra, Schwaab, Ira, Chandran, Urmila, Menkiszak, Janusz, Ekici, Arif B., Wilkens, Lynne R., Leminen, Arto, Modugno, Francesmary, Friel, Grace, Rothstein, Joseph H., Vergote, Ignace, Garcia-Closas, Montserrat, Hildebrandt, Michelle A.T., Sobiczewski, Piotr, Kelemen, Linda E., Pharoah, Paul D.P., Moysich, Kirsten, Knutson, Keith L., Cunningham, Julie M., Fridley, Brooke L., Goode, Ellen L., Trabert, B , Pelttari, L M , Nevanlinna, H , Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , Kiemeney, Lambertus A , Kjaer, Susanne K , Ramus, Susan J , Tworoger, Shelley S , Hein, Alexander , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Szafron, Lukasz M , Moysich, Kirsten , Orlow, Irene , Campbell, Ian G , Bamlet, William R , Menkiszak, Janusz , Brown, Robert , Fogarty, Zachary C , Flanagan, James M , Heitz, Florian , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , García-Closas, Montserrat , Severi, Gianluca , Ekici, Arif B , Bogdanova, Natalia V , Chenevix-Trench, Georgia , Høgdall, Estrid , Høgdall, Claus K , Lubinski, Jan , Baglietto, Laura , Goodman, Marc T , Bandera, Elisa V.
Cancer Research | November 22, 2013 | Volume: 74 | Issue: 3 | Pages: 852-861
Abstract A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1α (IL1A) is both regulated by and able to activate NF-κB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-κB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76–0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75–0.95; P = 0.006). Considering a multiple-testing–corrected significance threshold of P < 2.5 × 10−5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79–0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted. Cancer Res; 74(3); 852–61. ©2013 AACR.
Combined and Interactive Effects of Environmental and GWAS-Identified Risk Factors in Ovarian Cancer
Pearce, Celeste Leigh, Rossing, Mary Anne, Lee, Alice W. , Ness, Roberta B., Webb, Penelope M. , Cancer), for Australian Cancer Study (Ovarian, Group, and Australian Ovarian Cancer Study, Chenevix‐Trench, Georgia , Jordan, Susan M., Stram, Douglas, Chang‐Claude, Jenny, Hein, Rebecca, Nickels, Stefan , Lurie, Galina, Thompson, Pamela J., Carney, Michael E., Goodman, Marc T. , Moysich, Kirsten B., Høgdall, Estrid , Jensen, Allan , Goode, Ellen L. , Cunningham, Julie M. , Vierkant, Robert A. , Gayther, Simon A. , Menon, Usha , Ramus, Susan J. , Brinton, Louise A. , Wentzensen, Nicolas , Lissowska, Jolanta , García‐Closas, Montserrat , Massuger, Leon F.A.G. , Kiemeney, Lambertus A. , Altena, Anne M. van , Aben, Katja K.H. , Iversen, Edwin S., McGuire, Valerie, Moorman, Patricia G. , Pike, Malcolm C. , Sieh, Weiva , Terry, Kathryn L. , Whittemore, Alice S. , Wu, Anna H. , Schildkraut, Joellen M. , Kjær, Susanne K. , Jordan, Susan J. , Cancer), for Australian Cancer Study (Ovarian, Group, and Australian Ovarian Cancer Study, Jordan, Susan M., Fridley, Brooke L. , Weber, Rachel Palmieri , Ziogas, Argyrios , Anton‐Culver, Hoda , Gentry‐Maharaj, Aleksandra , Berchuck, Andrew , Doherty, Jennifer A. , Pharoah, Paul D.P. , Risch, Harvey A. , Stram, Daniel O. , Kiemeney, Lambertus A , Kjaer, Susanne K , Ramus, Susan J , Webb, Penelope M , Jensen, Allan , Vierkant, Robert A , Menon, Usha , Moysich, Kirsten , Lissowska, Jolanta , Sieh, Weiva , García-Closas, Montserrat , Chenevix-Trench, Georgia , Høgdall, Estrid , Goodman, Marc T
Cancer Epidemiology, Biomarkers & Prevention | March 6, 2013 | Volume: 22 | Issue: 5 | Pages: 880-890
10.1158/1055-9965.epi-12-1030-t
Abstract Background: There are several well-established environmental risk factors for ovarian cancer, and recent genome-wide association studies have also identified six variants that influence disease risk. However, the interplay between such risk factors and susceptibility loci has not been studied. Methods: Data from 14 ovarian cancer case–control studies were pooled, and stratified analyses by each environmental risk factor with tests for heterogeneity were conducted to determine the presence of interactions for all histologic subtypes. A genetic “risk score” was created to consider the effects of all six variants simultaneously. A multivariate model was fit to examine the association between all environmental risk factors and genetic risk score on ovarian cancer risk. Results: Among 7,374 controls and 5,566 cases, there was no statistical evidence of interaction between the six SNPs or genetic risk score and the environmental risk factors on ovarian cancer risk. In a main effects model, women in the highest genetic risk score quartile had a 65% increased risk of ovarian cancer compared with women in the lowest [95% confidence interval (CI), 1.48–1.84]. Analyses by histologic subtype yielded risk differences across subtype for endometriosis (Phet < 0.001), parity (Phet < 0.01), and tubal ligation (Phet = 0.041). Conclusions: The lack of interactions suggests that a multiplicative model is the best fit for these data. Under such a model, we provide a robust estimate of the effect of each risk factor that sets the stage for absolute risk prediction modeling that considers both environmental and genetic risk factors. Further research into the observed differences in risk across histologic subtype is warranted. Cancer Epidemiol Biomarkers Prev; 22(5); 880–90. ©2013 AACR.