20 results on '"Iskierka-Jazdzewska E"'
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2. Identification of novel genetic loci for risk of multiple myeloma by functional annotation.
- Author
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Macauda, A., Briem, K., Clay-Gilmour, A., Cozen, W., Försti, A., Giaccherini, M., Corradi, C., Sainz, J., Niazi, Y., Horst, R. ter, Li, Y., Netea, M.G., Vogel, U., Hemminki, K., Slager, S.L., Varkonyi, J., Andersen, V., Iskierka-Jazdzewska, E., Mártinez-Lopez, J., Zaucha, J., Camp, N.J., Rajkumar, S.V., Druzd-Sitek, A., Bhatti, P., Chanock, S.J., Kumar, S.K., Subocz, E., Mazur, G., Landi, S., Machiela, M.J., Jerez, A., Norman, A.D., Hildebrandt, M.A., Kadar, K., Berndt, S.I., Ziv, E., Buda, G., Nagler, A., Dumontet, C., Raźny, M., Watek, M., Butrym, A., Grzasko, N., Dudzinski, M., Rybicka-Ramos, M., Matera, E.L., García-Sanz, R., Goldschmidt, H., Jamroziak, K., Jurczyszyn, A., Clavero, E., Giles, G.G., Pelosini, M., Zawirska, D., Kruszewski, M., Marques, H., Haastrup, E., Sánchez-Maldonado, J.M., Bertsch, U., Rymko, M., Raab, M.S., Brown, E.E., Hofmann, J.N., Vachon, C., Campa, D., Canzian, F., Macauda, A., Briem, K., Clay-Gilmour, A., Cozen, W., Försti, A., Giaccherini, M., Corradi, C., Sainz, J., Niazi, Y., Horst, R. ter, Li, Y., Netea, M.G., Vogel, U., Hemminki, K., Slager, S.L., Varkonyi, J., Andersen, V., Iskierka-Jazdzewska, E., Mártinez-Lopez, J., Zaucha, J., Camp, N.J., Rajkumar, S.V., Druzd-Sitek, A., Bhatti, P., Chanock, S.J., Kumar, S.K., Subocz, E., Mazur, G., Landi, S., Machiela, M.J., Jerez, A., Norman, A.D., Hildebrandt, M.A., Kadar, K., Berndt, S.I., Ziv, E., Buda, G., Nagler, A., Dumontet, C., Raźny, M., Watek, M., Butrym, A., Grzasko, N., Dudzinski, M., Rybicka-Ramos, M., Matera, E.L., García-Sanz, R., Goldschmidt, H., Jamroziak, K., Jurczyszyn, A., Clavero, E., Giles, G.G., Pelosini, M., Zawirska, D., Kruszewski, M., Marques, H., Haastrup, E., Sánchez-Maldonado, J.M., Bertsch, U., Rymko, M., Raab, M.S., Brown, E.E., Hofmann, J.N., Vachon, C., Campa, D., and Canzian, F.
- Abstract
Contains fulltext : 299996.pdf (Publisher’s version ) (Open Access), 01 november 2023
- Published
- 2023
3. Common gene variants within 3'-untranslated regions as modulators of multiple myeloma risk and survival
- Author
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Melaiu, O., Macauda, A., Sainz, J., Calvetti, D., Facioni, M.S., Maccari, G., Horst, R. ter, Netea, M.G., Li, Y., Grząśko, N., Moreno, V., Jurczyszyn, A., Jerez, A., Watek, M., Varkonyi, J., Garcia-Sanz, R., Kruszewski, M., Dudziński, M., Kadar, K., Jacobsen, S.E. Hove, Mazur, G., Andersen, V., Rybicka, M., Zawirska, D., Raźny, M., Zaucha, J.M., Ostrovsky, O., Iskierka-Jazdzewska, E., Reis, R.M., Stępień, A., Beider, K., Nagler, A., Druzd-Sitek, A., Marques, H., Martìnez-Lopez, J., Lesueur, F., Avet-Loiseau, H., Vangsted, A.J., Krawczyk-Kulis, M., Butrym, A., Jamroziak, K., Dumontet, C., Vogel, U., Rymko, M., Pelosini, M., Subocz, E., Szombath, G., Sarasquete, M.E., Silvestri, R., Morani, F., Landi, S., Campa, D., Canzian, F., Gemignani, F., Melaiu, O., Macauda, A., Sainz, J., Calvetti, D., Facioni, M.S., Maccari, G., Horst, R. ter, Netea, M.G., Li, Y., Grząśko, N., Moreno, V., Jurczyszyn, A., Jerez, A., Watek, M., Varkonyi, J., Garcia-Sanz, R., Kruszewski, M., Dudziński, M., Kadar, K., Jacobsen, S.E. Hove, Mazur, G., Andersen, V., Rybicka, M., Zawirska, D., Raźny, M., Zaucha, J.M., Ostrovsky, O., Iskierka-Jazdzewska, E., Reis, R.M., Stępień, A., Beider, K., Nagler, A., Druzd-Sitek, A., Marques, H., Martìnez-Lopez, J., Lesueur, F., Avet-Loiseau, H., Vangsted, A.J., Krawczyk-Kulis, M., Butrym, A., Jamroziak, K., Dumontet, C., Vogel, U., Rymko, M., Pelosini, M., Subocz, E., Szombath, G., Sarasquete, M.E., Silvestri, R., Morani, F., Landi, S., Campa, D., Canzian, F., and Gemignani, F.
- Abstract
Contains fulltext : 232394.pdf (Publisher’s version ) (Closed access), We evaluated the association between germline genetic variants located within the 3'-untranlsated region (polymorphic 3'UTR, ie, p3UTR) of candidate genes involved in multiple myeloma (MM). We performed a case-control study within the International Multiple Myeloma rESEarch (IMMEnSE) consortium, consisting of 3056 MM patients and 1960 controls recruited from eight countries. We selected p3UTR of six genes known to act in different pathways relevant in MM pathogenesis, namely KRAS (rs12587 and rs7973623), VEGFA (rs10434), SPP1 (rs1126772), IRF4 (rs12211228) and IL10 (rs3024496). We found that IL10-rs3024496 was associated with increased risk of developing MM and with a worse overall survival of MM patients. The variant allele was assayed in a vector expressing eGFP chimerized with the IL10 3'-UTR and it was found functionally active following transfection in human myeloma cells. In this experiment, the A-allele caused a lower expression of the reporter gene and this was also in agreement with the in vivo expression of mRNA measured in whole blood as reported in the GTEx portal. Overall, these data are suggestive of an effect of the IL10-rs3024496 SNP on the regulation of IL10 mRNA expression and it could have clinical implications for better characterization of MM patients in terms of prognosis.
- Published
- 2021
4. Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients.
- Author
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Vachon C.M., Canzian F., Campa D., Watek M., Jurczyszyn A., Brown E.E., Berndt S., Butrym A., Norman A.D., Gemignani F., Slager S.L., Macauda A., Piredda C., Clay-Gilmour A.I., Sainz J., Buda G., Markiewicz M., Barington T., Ziv E., Hildebrandt M.A.T., Belachew A.A., Varkonyi J., Prejzner W., Druzd-Sitek A., Spinelli J., Andersen N.F., Hofmann J.N., Dudzinski M., Martinez-Lopez J., Iskierka-Jazdzewska E., Milne R.L., Mazur G., Giles G.G., Ebbesen L.H., Rymko M., Jamroziak K., Subocz E., Reis R.M., Garcia-Sanz R., Suska A., Haastrup E.K., Zawirska D., Grzasko N., Vangsted A.J., Dumontet C., Kruszewski M., Dutka M., Camp N.J., Waller R.G., Tomczak W., Pelosini M., Razny M., Marques H., Abildgaard N., Vachon C.M., Canzian F., Campa D., Watek M., Jurczyszyn A., Brown E.E., Berndt S., Butrym A., Norman A.D., Gemignani F., Slager S.L., Macauda A., Piredda C., Clay-Gilmour A.I., Sainz J., Buda G., Markiewicz M., Barington T., Ziv E., Hildebrandt M.A.T., Belachew A.A., Varkonyi J., Prejzner W., Druzd-Sitek A., Spinelli J., Andersen N.F., Hofmann J.N., Dudzinski M., Martinez-Lopez J., Iskierka-Jazdzewska E., Milne R.L., Mazur G., Giles G.G., Ebbesen L.H., Rymko M., Jamroziak K., Subocz E., Reis R.M., Garcia-Sanz R., Suska A., Haastrup E.K., Zawirska D., Grzasko N., Vangsted A.J., Dumontet C., Kruszewski M., Dutka M., Camp N.J., Waller R.G., Tomczak W., Pelosini M., Razny M., Marques H., and Abildgaard N.
- Abstract
Gene expression profiling can be used for predicting survival in multiple myeloma (MM) and identifying patients who will benefit from particular types of therapy. Some germline single nucleotide polymorphisms (SNPs) act as expression quantitative trait loci (eQTLs) showing strong associations with gene expression levels. We performed an association study to test whether eQTLs of genes reported to be associated with prognosis of MM patients are directly associated with measures of adverse outcome. Using the genotype-tissue expression portal, we identified a total of 16 candidate genes with at least one eQTL SNP associated with their expression with P < 10-7 either in EBV-transformed B-lymphocytes or whole blood. We genotyped the resulting 22 SNPs in 1327 MM cases from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and examined their association with overall survival (OS) and progression-free survival (PFS), adjusting for age, sex, country of origin and disease stage. Three polymorphisms in two genes (TBRG4-rs1992292, TBRG4-rs2287535 and ENTPD1-rs2153913) showed associations with OS at P <.05, with the former two also associated with PFS. The associations of two polymorphisms in TBRG4 with OS were replicated in 1277 MM cases from the International Lymphoma Epidemiology (InterLymph) Consortium. A meta-analysis of the data from IMMEnSE and InterLymph (2579 cases) showed that TBRG4-rs1992292 is associated with OS (hazard ratio = 1.14, 95% confidence interval 1.04-1.26, P =.007). In conclusion, we found biologically a plausible association between a SNP in TBRG4 and OS of MM patients.Copyright © 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.
- Published
- 2021
5. Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients
- Author
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Macauda, A, Piredda, C, Clay-Gilmour, A, Sainz, J, Buda, G, Markiewicz, M, Barington, T, Ziv, E, Hildebrandt, MAT, Belachew, AA, Varkonyi, J, Prejzner, W, Druzd-Sitek, A, Spinelli, J, Andersen, NF, Hofmann, JN, Dudzinski, M, Martinez-Lopez, J, Iskierka-Jazdzewska, E, Milne, RL, Mazur, G, Giles, GG, Ebbesen, LH, Rymko, M, Jamroziak, K, Subocz, E, Reis, RM, Garcia-Sanz, R, Suska, A, Haastrup, EK, Zawirska, D, Grzasko, N, Vangsted, AJ, Dumontet, C, Kruszewski, M, Dutka, M, Camp, NJ, Waller, RG, Tomczak, W, Pelosini, M, Razny, M, Marques, H, Abildgaard, N, Watek, M, Jurczyszyn, A, Brown, EE, Berndt, S, Butrym, A, Vachon, CM, Norman, AD, Slager, SL, Gemignani, F, Canzian, F, Campa, D, Macauda, A, Piredda, C, Clay-Gilmour, A, Sainz, J, Buda, G, Markiewicz, M, Barington, T, Ziv, E, Hildebrandt, MAT, Belachew, AA, Varkonyi, J, Prejzner, W, Druzd-Sitek, A, Spinelli, J, Andersen, NF, Hofmann, JN, Dudzinski, M, Martinez-Lopez, J, Iskierka-Jazdzewska, E, Milne, RL, Mazur, G, Giles, GG, Ebbesen, LH, Rymko, M, Jamroziak, K, Subocz, E, Reis, RM, Garcia-Sanz, R, Suska, A, Haastrup, EK, Zawirska, D, Grzasko, N, Vangsted, AJ, Dumontet, C, Kruszewski, M, Dutka, M, Camp, NJ, Waller, RG, Tomczak, W, Pelosini, M, Razny, M, Marques, H, Abildgaard, N, Watek, M, Jurczyszyn, A, Brown, EE, Berndt, S, Butrym, A, Vachon, CM, Norman, AD, Slager, SL, Gemignani, F, Canzian, F, and Campa, D
- Abstract
Gene expression profiling can be used for predicting survival in multiple myeloma (MM) and identifying patients who will benefit from particular types of therapy. Some germline single nucleotide polymorphisms (SNPs) act as expression quantitative trait loci (eQTLs) showing strong associations with gene expression levels. We performed an association study to test whether eQTLs of genes reported to be associated with prognosis of MM patients are directly associated with measures of adverse outcome. Using the genotype-tissue expression portal, we identified a total of 16 candidate genes with at least one eQTL SNP associated with their expression with P < 10-7 either in EBV-transformed B-lymphocytes or whole blood. We genotyped the resulting 22 SNPs in 1327 MM cases from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and examined their association with overall survival (OS) and progression-free survival (PFS), adjusting for age, sex, country of origin and disease stage. Three polymorphisms in two genes (TBRG4-rs1992292, TBRG4-rs2287535 and ENTPD1-rs2153913) showed associations with OS at P < .05, with the former two also associated with PFS. The associations of two polymorphisms in TBRG4 with OS were replicated in 1277 MM cases from the International Lymphoma Epidemiology (InterLymph) Consortium. A meta-analysis of the data from IMMEnSE and InterLymph (2579 cases) showed that TBRG4-rs1992292 is associated with OS (hazard ratio = 1.14, 95% confidence interval 1.04-1.26, P = .007). In conclusion, we found biologically a plausible association between a SNP in TBRG4 and OS of MM patients.
- Published
- 2021
6. Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma
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Obazee, O., Archibugi, L., Andriulli, A., Soucek, P., Malecka-Panas, E., Ivanauskas, A., Johnson, T., Gazouli, M., Pausch, T., Lawlor, R. T., Cavestro, G. M., Milanetto, A. C., Di Leo, M., Pasquali, C., Hegyi, P., Szentesi, A., Radu, C. E., Gheorghe, C., Theodoropoulos, G. E., Bergmann, F., Brenner, H., Vodickova, L., Katzke, V., Campa, D., Strobel, O., Kaiser, J., Pezzilli, R., Federici, F., Mohelnikova-Duchonova, B., Boggi, U., Lemstrova, R., Johansen, J. S., Bojesen, S. E., Chen, I., Jensen, B. V., Capurso, G., Pazienza, V., Dervenis, C., Sperti, C., Mambrini, A., Hackert, T., Kaaks, R., Basso, D., Talar-Wojnarowska, R., Maiello, E., Izbicki, J. R., Cuk, K., Saum, K. U., Cantore, M., Kupcinskas, J., Palmieri, O., Delle Fave, G., Landi, S., Salvia, R., Fogar, P., Vashist, Y. K., Scarpa, A., Vodicka, P., Tjaden, C., Iskierka-Jazdzewska, E., Canzian, F., Obazee, O., Archibugi, L., Andriulli, A., Soucek, P., Malecka-Panas, E., Ivanauskas, A., Johnson, T., Gazouli, M., Pausch, T., Lawlor, R. T., Cavestro, G. M., Milanetto, A. C., Di Leo, M., Pasquali, C., Hegyi, P., Szentesi, A., Radu, C. E., Gheorghe, C., Theodoropoulos, G. E., Bergmann, F., Brenner, H., Vodickova, L., Katzke, V., Campa, D., Strobel, O., Kaiser, J., Pezzilli, R., Federici, F., Mohelnikova-Duchonova, B., Boggi, U., Lemstrova, R., Johansen, J. S., Bojesen, S. E., Chen, I., Jensen, B. V., Capurso, G., Pazienza, V., Dervenis, C., Sperti, C., Mambrini, A., Hackert, T., Kaaks, R., Basso, D., Talar-Wojnarowska, R., Maiello, E., Izbicki, J. R., Cuk, K., Saum, K. U., Cantore, M., Kupcinskas, J., Palmieri, O., Delle Fave, G., Landi, S., Salvia, R., Fogar, P., Vashist, Y. K., Scarpa, A., Vodicka, P., Tjaden, C., Iskierka-Jazdzewska, E., and Canzian, F.
- Subjects
Male ,Cancer Research ,pancreatic cancer ,Genes, BRCA2 ,I157T ,Polymorphism, Single Nucleotide ,Humans ,Genetic Predisposition to Disease ,Germ-Line Mutation ,Aged ,BRCA2 Protein ,K3326X ,PANDoRA consortium ,rs11571833 ,rs17879961 ,Oncology ,Pancreatic cancer ,Middle Aged ,Pancreatic Neoplasms ,Checkpoint Kinase 2 ,Case-Control Studies ,Female ,Carcinoma, Pancreatic Ductal - Abstract
Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values
- Published
- 2018
7. Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma
- Author
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Obazee, O. Archibugi, L. Andriulli, A. Soucek, P. Małecka-Panas, E. Ivanauskas, A. Johnson, T. Gazouli, M. Pausch, T. Lawlor, R.T. Cavestro, G.M. Milanetto, A.C. Di Leo, M. Pasquali, C. Hegyi, P. Szentesi, A. Radu, C.E. Gheorghe, C. Theodoropoulos, G.E. Bergmann, F. Brenner, H. Vodickova, L. Katzke, V. Campa, D. Strobel, O. Kaiser, J. Pezzilli, R. Federici, F. Mohelnikova-Duchonova, B. Boggi, U. Lemstrova, R. Johansen, J.S. Bojesen, S.E. Chen, I. Jensen, B.V. Capurso, G. Pazienza, V. Dervenis, C. Sperti, C. Mambrini, A. Hackert, T. Kaaks, R. Basso, D. Talar-Wojnarowska, R. Maiello, E. Izbicki, J.R. Cuk, K. Saum, K.U. Cantore, M. Kupcinskas, J. Palmieri, O. Delle Fave, G. Landi, S. Salvia, R. Fogar, P. Vashist, Y.K. Scarpa, A. Vodicka, P. Tjaden, C. Iskierka-Jazdzewska, E. Canzian, F.
- Abstract
Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values
- Published
- 2019
8. Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma
- Author
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Obazee, O, Archibugi, L, Andriulli, A, Soucek, P, Małecka-Panas, E, Ivanauskas, A, Johnson, T, Gazouli, M, Pausch, T, Lawlor, R T, Cavestro, G M, Milanetto, A C, Di Leo, M, Pasquali, C, Hegyi, P, Szentesi, A, Radu, C E, Gheorghe, C, Theodoropoulos, G E, Bergmann, F, Brenner, H, Vodickova, L, Katzke, V, Campa, D, Strobel, O, Kaiser, J, Pezzilli, R, Federici, F, Mohelnikova-Duchonova, B, Boggi, U, Lemstrova, R, Johansen, J S, Bojesen, S E, Chen, I, Jensen, B V, Capurso, G, Pazienza, V, Dervenis, C, Sperti, C, Mambrini, A, Hackert, T, Kaaks, R, Basso, D, Talar-Wojnarowska, R, Maiello, E, Izbicki, J R, Cuk, K, Saum, K U, Cantore, M, Kupcinskas, J, Palmieri, O, Delle Fave, G, Landi, S, Salvia, R, Fogar, P, Vashist, Y K, Scarpa, A, Vodicka, P, Tjaden, C, Iskierka-Jazdzewska, E, Canzian, F, Obazee, O, Archibugi, L, Andriulli, A, Soucek, P, Małecka-Panas, E, Ivanauskas, A, Johnson, T, Gazouli, M, Pausch, T, Lawlor, R T, Cavestro, G M, Milanetto, A C, Di Leo, M, Pasquali, C, Hegyi, P, Szentesi, A, Radu, C E, Gheorghe, C, Theodoropoulos, G E, Bergmann, F, Brenner, H, Vodickova, L, Katzke, V, Campa, D, Strobel, O, Kaiser, J, Pezzilli, R, Federici, F, Mohelnikova-Duchonova, B, Boggi, U, Lemstrova, R, Johansen, J S, Bojesen, S E, Chen, I, Jensen, B V, Capurso, G, Pazienza, V, Dervenis, C, Sperti, C, Mambrini, A, Hackert, T, Kaaks, R, Basso, D, Talar-Wojnarowska, R, Maiello, E, Izbicki, J R, Cuk, K, Saum, K U, Cantore, M, Kupcinskas, J, Palmieri, O, Delle Fave, G, Landi, S, Salvia, R, Fogar, P, Vashist, Y K, Scarpa, A, Vodicka, P, Tjaden, C, Iskierka-Jazdzewska, E, and Canzian, F
- Abstract
Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom ) = 1.78, 95% confidence interval (CI) = 1.26-2.52, p = 1.19 × 10-3 and ORdom = 1.74, 95% CI = 1.15-2.63, p = 8.57 × 10-3 , respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history.
- Published
- 2019
9. Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma
- Author
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Obazee, O., primary, Archibugi, L., additional, Andriulli, A., additional, Soucek, P., additional, Małecka-Panas, E., additional, Ivanauskas, A., additional, Johnson, T., additional, Gazouli, M., additional, Pausch, T., additional, Lawlor, R. T., additional, Cavestro, G. M., additional, Milanetto, A. C., additional, Di Leo, M., additional, Pasquali, C., additional, Hegyi, P., additional, Szentesi, A., additional, Radu, C. E., additional, Gheorghe, C., additional, Theodoropoulos, G. E., additional, Bergmann, F., additional, Brenner, H., additional, Vodickova, L., additional, Katzke, V., additional, Campa, D., additional, Strobel, O., additional, Kaiser, J., additional, Pezzilli, R., additional, Federici, F., additional, Mohelnikova-Duchonova, B., additional, Boggi, U., additional, Lemstrova, R., additional, Johansen, J. S., additional, Bojesen, S. E., additional, Chen, I., additional, Jensen, B. V., additional, Capurso, G., additional, Pazienza, V., additional, Dervenis, C., additional, Sperti, C., additional, Mambrini, A., additional, Hackert, T., additional, Kaaks, R., additional, Basso, D., additional, Talar-Wojnarowska, R., additional, Maiello, E., additional, Izbicki, J. R., additional, Cuk, K., additional, Saum, K. U., additional, Cantore, M., additional, Kupcinskas, J., additional, Palmieri, O., additional, Delle Fave, G., additional, Landi, S., additional, Salvia, R., additional, Fogar, P., additional, Vashist, Y. K., additional, Scarpa, A., additional, Vodicka, P., additional, Tjaden, C., additional, Iskierka-Jazdzewska, E., additional, and Canzian, F., additional
- Published
- 2019
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10. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21
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Zhang, M. Wang, Z. Obazee, O. Jia, J. Childs, E.J. Hoskins, J. Figlioli, G. Mocci, E. Collins, I. Chung, C.C. Hautman, C. Arslan, A.A. Beane-Freeman, L. Bracci, P.M. Buring, J. Duell, E.J. Gallinger, S. Giles, G.G. Goodman, G.E. Goodman, P.J. Kamineni, A. Kolonel, L.N. Kulke, M.H. Malats, N. Olson, S.H. Sesso, H.D. Visvanathan, K. White, E. Zheng, W. Abnet, C.C. Albanes, D. Andreotti, G. Brais, L. Bas Bueno-de-Mesquita, H. Basso, D. Berndt, S.I. Boutron-Ruault, M.-C. Bijlsma, M.F. Brenner, H. Burdette, L. Campa, D. Caporaso, N.E. Capurso, G. Cavestro, G.M. Cotterchio, M. Costello, E. Elena, J. Boggi, U. Michael Gaziano, J. Gazouli, M. Giovannucci, E.L. Goggins, M. Gross, M. Haiman, C.A. Hassan, M. Helzlsouer, K.J. Hu, N. Hunter, D.J. Iskierka-Jazdzewska, E. Jenab, M. Kaaks, R. Key, T.J. Khaw, K.-T. Klein, E.A. Kogevinas, M. Krogh, V. Kupcinskas, J. Kurtz, R.C. Landi, M.T. Landi, S. Marchand, L.L. Mambrini, A. Mannisto, S. Milne, R.L. Neale, R.E. Oberg, A.L. Panico, S. Patel, A.V. Peeters, P.H.M. Peters, U. Pezzilli, R. Porta, M. Purdue, M. Ramón Quiros, J. Riboli, E. Rothman, N. Scarpa, A. Scelo, G. Shu, X.-O. Silverman, D.T. Soucek, P. Strobel, O. Sund, M. Malecka-Panas, E. Taylor, P.R. Tavano, F. Travis, R.C. Thornquist, M. Tjønneland, A. Tobias, G.S. Trichopoulos, D. Vashist, Y. Vodicka, P. Wactawski-Wende, J. Wentzensen, N. Yu, H. Yu, K. Zeleniuch-Jacquotte, A. Kooperberg, C. Risch, H.A. Jacobs, E.J. Li, D. Fuchs, C. Hoover, R. Hartge, P. Chanock, S.J. Petersen, G.M. Stolzenberg-Solomon, R.S. Wolpin, B.M. Kraft, P. Klein, A.P. Canzian, F. Amundadottir, L.T.
- Abstract
Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10-15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10-9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10-8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10-8). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10-4-2.0x10-3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
- Published
- 2016
11. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21
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Zhang, M, Wang, Z, Obazee, O, Jia, J, Childs, EJ, Hoskins, J, Figlioli, G, Mocci, E, Collins, I, Chung, CC, Hautman, C, Arslan, AA, Beane-Freeman, L, Bracci, PM, Buring, J, Duell, EJ, Gallinger, S, Giles, GG, Goodman, GE, Goodman, PJ, Kamineni, A, Kolonel, LN, Kulke, MH, Malats, N, Olson, SH, Sesso, HD, Visvanathan, K, White, E, Zheng, W, Abnet, CC, Albanes, D, Andreotti, G, Brais, L, Bueno-de-Mesquita, HB, Basso, D, Berndt, SI, Boutron-Ruault, M-C, Bijlsma, MF, Brenner, H, Burdette, L, Campa, D, Caporaso, NE, Capurso, G, Cavestro, GM, Cotterchio, M, Costello, E, Elena, J, Boggi, U, Gaziano, JM, Gazouli, M, Giovannucci, EL, Goggins, M, Gross, M, Haiman, CA, Hassan, M, Helzlsouer, KJ, Hu, N, Hunter, DJ, Iskierka-Jazdzewska, E, Jenab, M, Kaaks, R, Key, TJ, Khaw, K-T, Klein, EA, Kogevinas, M, Krogh, V, Kupcinskas, J, Kurtz, RC, Landi, MT, Landi, S, Le Marchand, L, Mambrini, A, Mannisto, S, Milne, RL, Neale, RE, Oberg, AL, Panico, S, Patel, AV, Peeters, PHM, Peters, U, Pezzilli, R, Porta, M, Purdue, M, Ramon Quiros, J, Riboli, E, Rothman, N, Scarpa, A, Scelo, G, Shu, X-O, Silverman, DT, Soucek, P, Strobel, O, Sund, M, Malecka-Panas, E, Taylor, PR, Tavano, F, Travis, RC, Thornquist, M, Tjonneland, A, Tobias, GS, Trichopoulos, D, Vashist, Y, Vodicka, P, Wactawski-Wende, J, Wentzensen, N, Yu, H, Yu, K, Zeleniuch-Jacquotte, A, Kooperberg, C, Risch, HA, Jacobs, EJ, Li, D, Fuchs, C, Hoover, R, Hartge, P, Chanock, SJ, Petersen, GM, Stolzenberg-Solomon, RS, Wolpin, BM, Kraft, P, Klein, AP, Canzian, F, Amundadottir, LT, Zhang, M, Wang, Z, Obazee, O, Jia, J, Childs, EJ, Hoskins, J, Figlioli, G, Mocci, E, Collins, I, Chung, CC, Hautman, C, Arslan, AA, Beane-Freeman, L, Bracci, PM, Buring, J, Duell, EJ, Gallinger, S, Giles, GG, Goodman, GE, Goodman, PJ, Kamineni, A, Kolonel, LN, Kulke, MH, Malats, N, Olson, SH, Sesso, HD, Visvanathan, K, White, E, Zheng, W, Abnet, CC, Albanes, D, Andreotti, G, Brais, L, Bueno-de-Mesquita, HB, Basso, D, Berndt, SI, Boutron-Ruault, M-C, Bijlsma, MF, Brenner, H, Burdette, L, Campa, D, Caporaso, NE, Capurso, G, Cavestro, GM, Cotterchio, M, Costello, E, Elena, J, Boggi, U, Gaziano, JM, Gazouli, M, Giovannucci, EL, Goggins, M, Gross, M, Haiman, CA, Hassan, M, Helzlsouer, KJ, Hu, N, Hunter, DJ, Iskierka-Jazdzewska, E, Jenab, M, Kaaks, R, Key, TJ, Khaw, K-T, Klein, EA, Kogevinas, M, Krogh, V, Kupcinskas, J, Kurtz, RC, Landi, MT, Landi, S, Le Marchand, L, Mambrini, A, Mannisto, S, Milne, RL, Neale, RE, Oberg, AL, Panico, S, Patel, AV, Peeters, PHM, Peters, U, Pezzilli, R, Porta, M, Purdue, M, Ramon Quiros, J, Riboli, E, Rothman, N, Scarpa, A, Scelo, G, Shu, X-O, Silverman, DT, Soucek, P, Strobel, O, Sund, M, Malecka-Panas, E, Taylor, PR, Tavano, F, Travis, RC, Thornquist, M, Tjonneland, A, Tobias, GS, Trichopoulos, D, Vashist, Y, Vodicka, P, Wactawski-Wende, J, Wentzensen, N, Yu, H, Yu, K, Zeleniuch-Jacquotte, A, Kooperberg, C, Risch, HA, Jacobs, EJ, Li, D, Fuchs, C, Hoover, R, Hartge, P, Chanock, SJ, Petersen, GM, Stolzenberg-Solomon, RS, Wolpin, BM, Kraft, P, Klein, AP, Canzian, F, and Amundadottir, LT
- Abstract
Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
- Published
- 2016
12. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21
- Author
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Anne Tjønneland, Jason W. Hoskins, Kala Visvanathan, Yogesh K. Vashist, Dimitrios Trichopoulos, Matthew H. Kulke, Ruth C. Travis, Charles S. Fuchs, Herbert Yu, Kai Yu, Phyllis J. Goodman, Michael Goggins, Jean Wactawski-Wende, Laurie Burdette, Joanne W. Elena, Andrea Mambrini, Petra H.M. Peeters, H. Bas Bueno-de-Mesquita, Maria Teresa Landi, Ulrike Peters, Mingfeng Zhang, Laurence N. Kolonel, Hermann Brenner, Elżbieta Iskierka-Jażdżewska, Robert C. Kurtz, Stephen J. Chanock, Marie-Christine Boutron-Ruault, Ann L. Oberg, Elio Riboli, Maarten F. Bijlsma, Eric J. Jacobs, Manolis Kogevinas, Evelina Mocci, Steven Gallinger, Jinping Jia, Mark P. Purdue, Raffaele Pezzilli, Harvey A. Risch, Demetrius Albanes, Irene Collins, Maria Gazouli, Michelle Cotterchio, Oliver Strobel, Erica J. Childs, Charles C. Chung, Geoffrey S. Tobias, J. Ramón Quirós, Núria Malats, Robert N. Hoover, Pavel Vodicka, Brian M. Wolpin, Ugo Boggi, Patricia Hartge, Gloria M. Petersen, Peter Kraft, Christopher Hautman, Gary E. Goodman, Manal Hassan, Donghui Li, Howard D. Sesso, Malin Sund, Julie E. Buring, Loic Le Marchand, Wei Zheng, Xiao-Ou Shu, Ewa Małecka-Panas, Pavel Soucek, Salvatore Panico, Nicolas Wentzensen, Graham G. Giles, Alpa V. Patel, Daniele Campa, Myron D. Gross, Ghislaine Scelo, J. Michael Gaziano, Juozas Kupcinskas, Debra T. Silverman, Laufey T. Amundadottir, Rachael S. Stolzenberg-Solomon, Neil E. Caporaso, Mazda Jenab, Sara H. Olson, Stefano Landi, Giulia Martina Cavestro, Aruna Kamineni, Laura Beane-Freeman, Roger L. Milne, Rachel E. Neale, Aldo Scarpa, Kathy J. Helzlsouer, Miquel Porta, Emily White, Eric J. Duell, Paige M. Bracci, Nan Hu, Federico Canzian, Eric A. Klein, Gabriele Capurso, Anne Zeleniuch-Jacquotte, Eithne Costello, David J. Hunter, Rudolf Kaaks, Sonja I. Berndt, Kay-Tee Khaw, Nathaniel Rothman, Christian C. Abnet, Francesca Tavano, Christopher A. Haiman, Zhaoming Wang, Ofure Obazee, Alan A. Arslan, Edward Giovannucci, Alison P. Klein, Daniela Basso, Charles Kooperberg, Philip R. Taylor, Satu Männistö, Timothy J. Key, Mark D. Thornquist, Gabriella Andreotti, Lauren K. Brais, Gisella Figlioli, Vittorio Krogh, University Medical Center Utrecht, Imperial College Trust, Cancer Research UK, Medical Research Council UK (MRC), National Institute for Health Research (NIHR), Cancer Research UK (Reino Unido), Medical Research Council (Reino Unido), National Institute for Health Research (Reino Unido), Zhang, Mingfeng, Wang, Zhaoming, Obazee, Ofure, Jia, Jinping, Childs, Erica J, Hoskins, Jason, Figlioli, Gisella, Mocci, Evelina, Collins, Irene, Chung, Charles C, Hautman, Christopher, Arslan, Alan A, Beane Freeman, Laura, Bracci, Paige M, Buring, Julie, Duell, Eric J, Gallinger, Steven, Giles, Graham G, Goodman, Gary E, Goodman, Phyllis J, Kamineni, Aruna, Kolonel, Laurence N, Kulke, Matthew H, Malats, Núria, Olson, Sara H, Sesso, Howard D, Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C, Albanes, Demetriu, Andreotti, Gabriella, Brais, Lauren, Bueno de Mesquita, H. Ba, Basso, Daniela, Berndt, Sonja I, Boutron Ruault, Marie Christine, Bijlsma, Maarten F, Brenner, Hermann, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E, Capurso, Gabriele, Cavestro, Giulia Martina, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Boggi, Ugo, Gaziano, J. Michael, Gazouli, Maria, Giovannucci, Edward L, Goggins, Michael, Gross, Myron, Haiman, Christopher A, Hassan, Manal, Helzlsouer, Kathy J, Hu, Nan, Hunter, David J, Iskierka Jazdzewska, Elzbieta, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay Tee, Klein, Eric A, Kogevinas, Manoli, Krogh, Vittorio, Kupcinskas, Juoza, Kurtz, Robert C, Landi, Maria T, Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L, Neale, Rachel E, Oberg, Ann L, Panico, Salvatore, Patel, Alpa V, Peeters, Petra H. M, Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Purdue, Mark, Quiros, J. Ramón, Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Scelo, Ghislaine, Shu, Xiao Ou, Silverman, Debra T, Soucek, Pavel, Strobel, Oliver, Sund, Malin, Małecka Panas, Ewa, Taylor, Philip R, Tavano, Francesca, Travis, Ruth C, Thornquist, Mark, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrio, Vashist, Yogesh, Vodicka, Pavel, Wactawski Wende, Jean, Wentzensen, Nicola, Yu, Herbert, Yu, Kai, Zeleniuch Jacquotte, Anne, Kooperberg, Charle, Risch, Harvey A, Jacobs, Eric J, Li, Donghui, Fuchs, Charle, Hoover, Robert, Hartge, Patricia, Chanock, Stephen J, Petersen, Gloria M, Stolzenberg Solomon, Rachael S, Wolpin, Brian M, Kraft, Peter, Klein, Alison P, Canzian, Federico, Amundadottir, Laufey T., Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, CCA -Cancer Center Amsterdam, Center of Experimental and Molecular Medicine, Radiotherapy, Zhang, M, Wang, Z, Obazee, O, Jia, J, Childs, Ej, Hoskins, J, Figlioli, G, Mocci, E, Collins, I, Chung, Cc, Hautman, C, Arslan, Aa, Beane Freeman, L, Bracci, Pm, Buring, J, Duell, Ej, Gallinger, S, Giles, Gg, Goodman, Ge, Goodman, Pj, Kamineni, A, Kolonel, Ln, Kulke, Mh, Malats, N, Olson, Sh, Sesso, Hd, Visvanathan, K, White, E, Zheng, W, Abnet, Cc, Albanes, D, Andreotti, G, Brais, L, Bueno de Mesquita, Hb, Basso, D, Berndt, Si, Boutron Ruault, Mc, Bijlsma, Mf, Brenner, H, Burdette, L, Campa, D, Caporaso, Ne, Capurso, G, Cavestro, GIULIA MARTINA, Cotterchio, M, Costello, E, Elena, J, Boggi, U, Gaziano, Jm, Gazouli, M, Giovannucci, El, Goggins, M, Gross, M, Haiman, Ca, Hassan, M, Helzlsouer, Kj, Hu, N, Hunter, Dj, Iskierka Jazdzewska, E, Jenab, M, Kaaks, R, Key, Tj, Khaw, Kt, Klein, Ea, Kogevinas, M, Krogh, V, Kupcinskas, J, Kurtz, Rc, Landi, Mt, Landi, S, Le Marchand, L, Mambrini, A, Mannisto, S, Milne, Rl, Neale, Re, Oberg, Al, Panico, S, Patel, Av, Peeters, Ph, Peters, U, Pezzilli, R, Porta, M, Purdue, M, Quiros, Jr, Riboli, E, Rothman, N, Scarpa, A, Scelo, G, Shu, Xo, Silverman, Dt, Soucek, P, Strobel, O, Sund, M, Małecka Panas, E, Taylor, Pr, Tavano, F, Travis, Rc, Thornquist, M, Tjønneland, A, Tobias, G, Trichopoulos, D, Vashist, Y, Vodicka, P, Wactawski Wende, J, Wentzensen, N, Yu, H, Yu, K, Zeleniuch Jacquotte, A, Kooperberg, C, Risch, Ha, Jacobs, Ej, Li, D, Fuchs, C, Hoover, R, Hartge, P, Chanock, Sj, Petersen, Gm, Stolzenberg Solomon, R, Wolpin, Bm, Kraft, P, Klein, Ap, Canzian, F, and Amundadottir, L. T.
- Subjects
0301 basic medicine ,Candidate gene ,Pancreatic disease ,GENETIC SUSCEPTIBILITY ,pancreatic cancer ,Datasets as Topic ,Genome-wide association study ,imputation ,TRET ,0302 clinical medicine ,Fine-mapping ,GWAS ,Imputation ,NR5A2 ,Pancreatic cancer ,Oncology ,Genotype ,Genetics ,3. Good health ,fine-mapping ,Chromosomes, Human, Pair 1 ,030220 oncology & carcinogenesis ,Chromosomes, Human, Pair 5 ,Chromosomes, Human, Pair 8 ,616.37-006.6 [udc] ,BLADDER-CANCER ,Single-nucleotide polymorphism ,GENOTYPE IMPUTATION ,BREAST ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Journal Article ,medicine ,Humans ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,Pàncrees -- Càncer ,Cancer och onkologi ,LONG-RANGE INTERACTION ,business.industry ,medicine.disease ,Pancreatic neoplasms ,genetics ,Polymorphism, single nucleotide ,RISK LOCI ,Fold change ,COMMON VARIANT ,Cromosomes ,Pancreatic Neoplasms ,030104 developmental biology ,Cancer and Oncology ,business ,Imputation (genetics) ,LRH-1 ,Priority Research Paper ,Genome-Wide Association Study - Abstract
Altres ajuts: The authors acknowledge the contribution of the staff of the Cancer Genomics Research Laboratory (CGR) at the National Cancer Institute, NIH, for their help throughout the project. This work was supported by the Intramural Research Program of the US National Institutes of Health (NIH), National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Additional acknowledgements for individual participating studies are listed in the Supplemental Materials. Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88×10 −15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22×10 −9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70×10 −8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L - TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7×10 −8). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5×10 −4 -2.0×10 −3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
- Published
- 2016
13. Identification of novel genetic loci for risk of multiple myeloma by functional annotation.
- Author
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Macauda A, Briem K, Clay-Gilmour A, Cozen W, Försti A, Giaccherini M, Corradi C, Sainz J, Niazi Y, Ter Horst R, Li Y, Netea MG, Vogel U, Hemminki K, Slager SL, Varkonyi J, Andersen V, Iskierka-Jazdzewska E, Mártinez-Lopez J, Zaucha J, Camp NJ, Rajkumar SV, Druzd-Sitek A, Bhatti P, Chanock SJ, Kumar SK, Subocz E, Mazur G, Landi S, Machiela MJ, Jerez A, Norman AD, Hildebrandt MAT, Kadar K, Berndt SI, Ziv E, Buda G, Nagler A, Dumontet C, Raźny M, Watek M, Butrym A, Grzasko N, Dudzinski M, Rybicka-Ramos M, Matera EL, García-Sanz R, Goldschmidt H, Jamroziak K, Jurczyszyn A, Clavero E, Giles GG, Pelosini M, Zawirska D, Kruszewski M, Marques H, Haastrup E, Sánchez-Maldonado JM, Bertsch U, Rymko M, Raab MS, Brown EE, Hofmann JN, Vachon C, Campa D, and Canzian F
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- Humans, Genetic Loci, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Multiple Myeloma genetics
- Published
- 2023
- Full Text
- View/download PDF
14. A pleiotropic variant in DNAJB4 is associated with multiple myeloma risk.
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Dicanio M, Giaccherini M, Clay-Gilmour A, Macauda A, Sainz J, Machiela MJ, Rybicka-Ramos M, Norman AD, Tyczyńska A, Chanock SJ, Barington T, Kumar SK, Bhatti P, Cozen W, Brown EE, Suska A, Haastrup EK, Orlowski RZ, Dudziński M, Garcia-Sanz R, Kruszewski M, Martinez-Lopez J, Beider K, Iskierka-Jazdzewska E, Pelosini M, Berndt SI, Raźny M, Jamroziak K, Rajkumar SV, Jurczyszyn A, Vangsted AJ, Collado PG, Vogel U, Hofmann JN, Petrini M, Butrym A, Slager SL, Ziv E, Subocz E, Giles GG, Andersen NF, Mazur G, Watek M, Lesueur F, Hildebrandt MAT, Zawirska D, Ebbesen LH, Marques H, Gemignani F, Dumontet C, Várkonyi J, Buda G, Nagler A, Druzd-Sitek A, Wu X, Kadar K, Camp NJ, Grzasko N, Waller RG, Vachon C, Canzian F, and Campa D
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- Humans, Oncogenes, Alleles, Phenotype, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic Predisposition to Disease, HSP40 Heat-Shock Proteins genetics, DNA-Binding Proteins genetics, RNA-Binding Proteins, Multiple Myeloma epidemiology, Multiple Myeloma genetics
- Abstract
Pleiotropy, which consists of a single gene or allelic variant affecting multiple unrelated traits, is common across cancers, with evidence for genome-wide significant loci shared across cancer and noncancer traits. This feature is particularly relevant in multiple myeloma (MM) because several susceptibility loci that have been identified to date are pleiotropic. Therefore, the aim of this study was to identify novel pleiotropic variants involved in MM risk using 28 684 independent single nucleotide polymorphisms (SNPs) from GWAS Catalog that reached a significant association (P < 5 × 10
-8 ) with their respective trait. The selected SNPs were analyzed in 2434 MM cases and 3446 controls from the International Lymphoma Epidemiology Consortium (InterLymph). The 10 SNPs showing the strongest associations with MM risk in InterLymph were selected for replication in an independent set of 1955 MM cases and 1549 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and 418 MM cases and 147 282 controls from the FinnGen project. The combined analysis of the three studies identified an association between DNAJB4-rs34517439-A and an increased risk of developing MM (OR = 1.22, 95%CI 1.13-1.32, P = 4.81 × 10-7 ). rs34517439-A is associated with a modified expression of the FUBP1 gene, which encodes a multifunctional DNA and RNA-binding protein that it was observed to influence the regulation of various genes involved in cell cycle regulation, among which various oncogenes and oncosuppressors. In conclusion, with a pleiotropic scan approach we identified DNAJB4-rs34517439 as a potentially novel MM risk locus., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)- Published
- 2023
- Full Text
- View/download PDF
15. Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?
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Macauda A, Clay-Gilmour A, Hielscher T, Hildebrandt MAT, Kruszewski M, Orlowski RZ, Kumar SK, Ziv E, Orciuolo E, Brown EE, Försti A, Waller RG, Machiela MJ, Chanock SJ, Camp NJ, Rymko M, Raźny M, Cozen W, Várkonyi J, Piredda C, Pelosini M, Belachew AA, Subocz E, Hemminki K, Rybicka-Ramos M, Giles GG, Milne RL, Hofmann JN, Zaucha JM, Vangsted AJ, Goldschmidt H, Rajkumar SV, Tomczak W, Sainz J, Butrym A, Watek M, Iskierka-Jazdzewska E, Buda G, Robinson DP, Jurczyszyn A, Dudziński M, Martinez-Lopez J, Sinnwell JP, Slager SL, Jamroziak K, Reis RMV, Weinhold N, Bhatti P, Carvajal-Carmona LG, Zawirska D, Norman AD, Mazur G, Berndt SI, Campa D, Vachon CM, and Canzian F
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- Genetic Predisposition to Disease, Humans, Polymorphism, Single Nucleotide, Risk Factors, Genome-Wide Association Study methods, Multiple Myeloma genetics
- Abstract
Background: Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g., colorectum and melanoma), risk loci have also been associated with patient survival., Methods: We explored the possible association of all the known risk variants and their polygenic risk score (PRS) with multiple myeloma overall survival (OS) in multiple populations of EA [the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the International Lymphoma Epidemiology consortium, CoMMpass, and the German GWAS] for a total of 3,748 multiple myeloma cases. Cox proportional hazards regression was used to assess the association between each risk SNP with OS under the allelic and codominant models of inheritance. All analyses were adjusted for age, sex, country of origin (for IMMEnSE) or principal components (for the others) and disease stage (ISS). SNP associations were meta-analyzed., Results: SNP associations were meta-analyzed. From the meta-analysis, two multiple myeloma risk SNPs were associated with OS (P < 0.05), specifically POT1-AS1-rs2170352 [HR = 1.37; 95% confidence interval (CI) = 1.09-1.73; P = 0.007] and TNFRSF13B-rs4273077 (HR = 1.19; 95% CI = 1.01-1.41; P = 0.04). The association between the combined 24 SNP MM-PRS and OS, however, was not significant., Conclusions: Overall, our results did not support an association between the majority of multiple myeloma risk SNPs and OS., Impact: This is the first study to investigate the association between multiple myeloma PRS and OS in multiple myeloma., (©2022 American Association for Cancer Research.)
- Published
- 2022
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16. Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients.
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Macauda A, Piredda C, Clay-Gilmour AI, Sainz J, Buda G, Markiewicz M, Barington T, Ziv E, Hildebrandt MAT, Belachew AA, Varkonyi J, Prejzner W, Druzd-Sitek A, Spinelli J, Andersen NF, Hofmann JN, Dudziński M, Martinez-Lopez J, Iskierka-Jazdzewska E, Milne RL, Mazur G, Giles GG, Ebbesen LH, Rymko M, Jamroziak K, Subocz E, Reis RM, Garcia-Sanz R, Suska A, Haastrup EK, Zawirska D, Grzasko N, Vangsted AJ, Dumontet C, Kruszewski M, Dutka M, Camp NJ, Waller RG, Tomczak W, Pelosini M, Raźny M, Marques H, Abildgaard N, Wątek M, Jurczyszyn A, Brown EE, Berndt S, Butrym A, Vachon CM, Norman AD, Slager SL, Gemignani F, Canzian F, and Campa D
- Subjects
- Aged, Female, Genetic Association Studies, Germ-Line Mutation, Humans, Male, Middle Aged, Multiple Myeloma genetics, Survival Analysis, Apyrase genetics, Gene Expression Profiling methods, Mitochondrial Proteins genetics, Multiple Myeloma mortality, Polymorphism, Single Nucleotide, Quantitative Trait Loci, RNA-Binding Proteins genetics
- Abstract
Gene expression profiling can be used for predicting survival in multiple myeloma (MM) and identifying patients who will benefit from particular types of therapy. Some germline single nucleotide polymorphisms (SNPs) act as expression quantitative trait loci (eQTLs) showing strong associations with gene expression levels. We performed an association study to test whether eQTLs of genes reported to be associated with prognosis of MM patients are directly associated with measures of adverse outcome. Using the genotype-tissue expression portal, we identified a total of 16 candidate genes with at least one eQTL SNP associated with their expression with P < 10
-7 either in EBV-transformed B-lymphocytes or whole blood. We genotyped the resulting 22 SNPs in 1327 MM cases from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and examined their association with overall survival (OS) and progression-free survival (PFS), adjusting for age, sex, country of origin and disease stage. Three polymorphisms in two genes (TBRG4-rs1992292, TBRG4-rs2287535 and ENTPD1-rs2153913) showed associations with OS at P < .05, with the former two also associated with PFS. The associations of two polymorphisms in TBRG4 with OS were replicated in 1277 MM cases from the International Lymphoma Epidemiology (InterLymph) Consortium. A meta-analysis of the data from IMMEnSE and InterLymph (2579 cases) showed that TBRG4-rs1992292 is associated with OS (hazard ratio = 1.14, 95% confidence interval 1.04-1.26, P = .007). In conclusion, we found biologically a plausible association between a SNP in TBRG4 and OS of MM patients., (© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)- Published
- 2021
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17. Cutaneous leukocytoclastic vasculitis at diagnosis of hairy cell leukemia successfully treated with vemurafenib and rituximab.
- Author
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Robak E, Jesionek-Kupnicka D, Iskierka-Jazdzewska E, Janus A, and Robak T
- Subjects
- Humans, Male, Middle Aged, Leukemia, Hairy Cell diagnosis, Leukemia, Hairy Cell drug therapy, Leukemia, Hairy Cell pathology, Rituximab administration & dosage, Vasculitis, Leukocytoclastic, Cutaneous diagnosis, Vasculitis, Leukocytoclastic, Cutaneous drug therapy, Vasculitis, Leukocytoclastic, Cutaneous pathology, Vemurafenib administration & dosage
- Published
- 2021
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18. Common gene variants within 3'-untranslated regions as modulators of multiple myeloma risk and survival.
- Author
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Melaiu O, Macauda A, Sainz J, Calvetti D, Facioni MS, Maccari G, Ter Horst R, Netea MG, Li Y, Grząśko N, Moreno V, Jurczyszyn A, Jerez A, Watek M, Varkonyi J, Garcia-Sanz R, Kruszewski M, Dudziński M, Kadar K, Jacobsen SEH, Mazur G, Andersen V, Rybicka M, Zawirska D, Raźny M, Zaucha JM, Ostrovsky O, Iskierka-Jazdzewska E, Reis RM, Stępień A, Beider K, Nagler A, Druzd-Sitek A, Marques H, Martìnez-Lopez J, Lesueur F, Avet-Loiseau H, Vangsted AJ, Krawczyk-Kulis M, Butrym A, Jamroziak K, Dumontet C, Vogel U, Rymko M, Pelosini M, Subocz E, Szombath G, Sarasquete ME, Silvestri R, Morani F, Landi S, Campa D, Canzian F, and Gemignani F
- Subjects
- Adult, Aged, Case-Control Studies, Female, Gene Expression Regulation, Neoplastic, Gene Frequency, Genotype, Humans, Male, Middle Aged, Multiple Myeloma diagnosis, Polymorphism, Single Nucleotide, RNA, Messenger genetics, RNA, Messenger metabolism, Risk Factors, Survival Analysis, 3' Untranslated Regions genetics, Genetic Predisposition to Disease genetics, Germ-Line Mutation, Multiple Myeloma genetics
- Abstract
We evaluated the association between germline genetic variants located within the 3'-untranlsated region (polymorphic 3'UTR, ie, p3UTR) of candidate genes involved in multiple myeloma (MM). We performed a case-control study within the International Multiple Myeloma rESEarch (IMMEnSE) consortium, consisting of 3056 MM patients and 1960 controls recruited from eight countries. We selected p3UTR of six genes known to act in different pathways relevant in MM pathogenesis, namely KRAS (rs12587 and rs7973623), VEGFA (rs10434), SPP1 (rs1126772), IRF4 (rs12211228) and IL10 (rs3024496). We found that IL10-rs3024496 was associated with increased risk of developing MM and with a worse overall survival of MM patients. The variant allele was assayed in a vector expressing eGFP chimerized with the IL10 3'-UTR and it was found functionally active following transfection in human myeloma cells. In this experiment, the A-allele caused a lower expression of the reporter gene and this was also in agreement with the in vivo expression of mRNA measured in whole blood as reported in the GTEx portal. Overall, these data are suggestive of an effect of the IL10-rs3024496 SNP on the regulation of IL10 mRNA expression and it could have clinical implications for better characterization of MM patients in terms of prognosis., (© 2020 Union for International Cancer Control.)
- Published
- 2021
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19. Long-term Efficacy of Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia: Results of the Polish Adult Leukemia Study Group Observational Study.
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Pula B, Iskierka-Jazdzewska E, Dlugosz-Danecka M, Szymczyk A, Hus M, Szeremet A, Drozd-Sokolowska J, Waszczuk-Gajda A, Zaucha JM, Holojda J, Piszczek W, Steckiewicz P, Wojciechowska M, Osowiecki M, Knopinska-Posluszny W, Dudzinski M, Zawirska D, Subocz E, Halka J, Pluta A, Wichary R, Kumiega B, Budziszewska BK, Jurczak W, Lech-Maranda E, Giannopoulos K, Robak T, and Jamroziak K
- Subjects
- Adenine analogs & derivatives, Adult, Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Drug Resistance, Neoplasm, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Male, Middle Aged, Piperidines, Poland, Protein Kinase Inhibitors adverse effects, Pyrazoles adverse effects, Pyrimidines adverse effects, Recurrence, Survival Analysis, Treatment Outcome, Antineoplastic Agents therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Protein Kinase Inhibitors therapeutic use, Pyrazoles therapeutic use, Pyrimidines therapeutic use
- Abstract
Background/aim: To study the long-term clinical efficacy and tolerability of ibrutinib monotherapy in real-world relapsed and refractory chronic lymphocytic leukemia (RR-CLL) patients outside clinical trials., Patients and Methods: Clinical data of 171 RR-CLL patients treated with ibrutinib were collected within the observational study of the Polish Adult Leukemia Study Group., Results: Median patient age was 64 years. Patients were pretreated with 3 (1-10) median lines of therapy, while 42 (24.6%) had 17p deletion. The median observation time was 40 months (range=1-59 months), while median ibrutinib monotherapy reached 37.5 months (range=0.4-59.2 months). Response was noted in 132 (77.2%) patients. The estimated 5-year progression-free survival (PFS) and overall survival (OS) rates were 61.1% (95%CI=49.3-70.9%) and 56.8% (95%CI=45.6-66.6%), respectively. At the time of analysis 97 (56.7%) remained under ibrutinib monotherapy., Conclusion: Ibrutinib is clinically effective and tolerable as a monotherapy in real-world RR-CLL patients., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2020
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20. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21.
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Zhang M, Wang Z, Obazee O, Jia J, Childs EJ, Hoskins J, Figlioli G, Mocci E, Collins I, Chung CC, Hautman C, Arslan AA, Beane-Freeman L, Bracci PM, Buring J, Duell EJ, Gallinger S, Giles GG, Goodman GE, Goodman PJ, Kamineni A, Kolonel LN, Kulke MH, Malats N, Olson SH, Sesso HD, Visvanathan K, White E, Zheng W, Abnet CC, Albanes D, Andreotti G, Brais L, Bueno-de-Mesquita HB, Basso D, Berndt SI, Boutron-Ruault MC, Bijlsma MF, Brenner H, Burdette L, Campa D, Caporaso NE, Capurso G, Cavestro GM, Cotterchio M, Costello E, Elena J, Boggi U, Gaziano JM, Gazouli M, Giovannucci EL, Goggins M, Gross M, Haiman CA, Hassan M, Helzlsouer KJ, Hu N, Hunter DJ, Iskierka-Jazdzewska E, Jenab M, Kaaks R, Key TJ, Khaw KT, Klein EA, Kogevinas M, Krogh V, Kupcinskas J, Kurtz RC, Landi MT, Landi S, Le Marchand L, Mambrini A, Mannisto S, Milne RL, Neale RE, Oberg AL, Panico S, Patel AV, Peeters PH, Peters U, Pezzilli R, Porta M, Purdue M, Quiros JR, Riboli E, Rothman N, Scarpa A, Scelo G, Shu XO, Silverman DT, Soucek P, Strobel O, Sund M, Małecka-Panas E, Taylor PR, Tavano F, Travis RC, Thornquist M, Tjønneland A, Tobias GS, Trichopoulos D, Vashist Y, Vodicka P, Wactawski-Wende J, Wentzensen N, Yu H, Yu K, Zeleniuch-Jacquotte A, Kooperberg C, Risch HA, Jacobs EJ, Li D, Fuchs C, Hoover R, Hartge P, Chanock SJ, Petersen GM, Stolzenberg-Solomon RS, Wolpin BM, Kraft P, Klein AP, Canzian F, and Amundadottir LT
- Subjects
- Datasets as Topic, Genome-Wide Association Study methods, Genotype, Humans, Polymorphism, Single Nucleotide genetics, Chromosomes, Human, Pair 1 genetics, Chromosomes, Human, Pair 5 genetics, Chromosomes, Human, Pair 8 genetics, Genetic Predisposition to Disease genetics, Pancreatic Neoplasms genetics
- Abstract
Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
- Published
- 2016
- Full Text
- View/download PDF
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