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Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma

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Harvard

Obazee, O, Archibugi, L, Andriulli, A, Soucek, P, Małecka-Panas, E, Ivanauskas, A, Johnson, T, Gazouli, M, Pausch, T, Lawlor, RT, Cavestro, GM, Milanetto, AC, Di Leo, M, Pasquali, C, Hegyi, P, Szentesi, A, Radu, CE, Gheorghe, C, Theodoropoulos, GE, 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, JS, Bojesen, SE, Chen, I, Jensen, BV, Capurso, G, Pazienza, V, Dervenis, C, Sperti, C, Mambrini, A, Hackert, T, Kaaks, R, Basso, D, Talar-Wojnarowska, R, Maiello, E, Izbicki, JR, Cuk, K, Saum, KU, Cantore, M, Kupcinskas, J, Palmieri, O, Delle Fave, G, Landi, S, Salvia, R, Fogar, P, Vashist, YK, Scarpa, A, Vodicka, P, Tjaden, C, Iskierka-Jazdzewska, E & Canzian, F 2019, 'Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma' International Journal of Cancer, bind 145, nr. 3, s. 686-693. https://doi.org/10.1002/ijc.32127

APA

Obazee, O., Archibugi, L., Andriulli, A., Soucek, P., Małecka-Panas, E., Ivanauskas, A., ... Canzian, F. (2019). Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma. International Journal of Cancer, 145(3), 686-693. https://doi.org/10.1002/ijc.32127

CBE

Obazee O, Archibugi L, Andriulli A, Soucek P, Małecka-Panas E, Ivanauskas A, Johnson T, Gazouli M, Pausch T, Lawlor RT, Cavestro GM, Milanetto AC, Di Leo M, Pasquali C, Hegyi P, Szentesi A, Radu CE, Gheorghe C, Theodoropoulos GE, 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 JS, Bojesen SE, Chen I, Jensen BV, Capurso G, Pazienza V, Dervenis C, Sperti C, Mambrini A, Hackert T, Kaaks R, Basso D, Talar-Wojnarowska R, Maiello E, Izbicki JR, Cuk K, Saum KU, Cantore M, Kupcinskas J, Palmieri O, Delle Fave G, Landi S, Salvia R, Fogar P, Vashist YK, Scarpa A, Vodicka P, Tjaden C, Iskierka-Jazdzewska E, Canzian F. 2019. Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma. International Journal of Cancer. 145(3):686-693. https://doi.org/10.1002/ijc.32127

MLA

Vancouver

Author

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. / Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma. I: International Journal of Cancer. 2019 ; Bind 145, Nr. 3. s. 686-693.

Bibtex

@article{4d014ccda5734b3f81a430ff09273113,
title = "Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma",
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 (OR dom) = 1.78, 95{\%} confidence interval (CI) = 1.26–2.52, p = 1.19 × 10 −3 and OR dom = 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.",
keywords = "Aged, BRCA2 Protein/genetics, Carcinoma, Pancreatic Ductal/genetics, Case-Control Studies, Checkpoint Kinase 2/genetics, Female, Genes, BRCA2, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Male, Middle Aged, Pancreatic Neoplasms/genetics, Polymorphism, Single Nucleotide",
author = "O Obazee and L Archibugi and A Andriulli and P Soucek and E Małecka-Panas and A Ivanauskas and T Johnson and M Gazouli and T Pausch and Lawlor, {R T} and Cavestro, {G M} and Milanetto, {A C} and {Di Leo}, M and C Pasquali and P Hegyi and A Szentesi and Radu, {C E} and C Gheorghe and Theodoropoulos, {G E} and F Bergmann and H Brenner and L Vodickova and V Katzke and D Campa and O Strobel and J Kaiser and R Pezzilli and F Federici and B Mohelnikova-Duchonova and U Boggi and R Lemstrova and Johansen, {J S} and Bojesen, {S E} and I Chen and Jensen, {B V} and G Capurso and V Pazienza and C Dervenis and C Sperti and A Mambrini and T Hackert and R Kaaks and D Basso and R Talar-Wojnarowska and E Maiello and Izbicki, {J R} and K Cuk and Saum, {K U} and M Cantore and J Kupcinskas and O Palmieri and {Delle Fave}, G and S Landi and R Salvia and P Fogar and Vashist, {Y K} and A Scarpa and P Vodicka and C Tjaden and E Iskierka-Jazdzewska and F Canzian",
note = "{\circledC} 2019 UICC.",
year = "2019",
month = "8",
day = "1",
doi = "10.1002/ijc.32127",
language = "English",
volume = "145",
pages = "686--693",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "JohnWiley & Sons, Inc",
number = "3",

}

RIS

TY - JOUR

T1 - Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma

AU - Obazee, O

AU - Archibugi, L

AU - Andriulli, A

AU - Soucek, P

AU - Małecka-Panas, E

AU - Ivanauskas, A

AU - Johnson, T

AU - Gazouli, M

AU - Pausch, T

AU - Lawlor, R T

AU - Cavestro, G M

AU - Milanetto, A C

AU - Di Leo, M

AU - Pasquali, C

AU - Hegyi, P

AU - Szentesi, A

AU - Radu, C E

AU - Gheorghe, C

AU - Theodoropoulos, G E

AU - Bergmann, F

AU - Brenner, H

AU - Vodickova, L

AU - Katzke, V

AU - Campa, D

AU - Strobel, O

AU - Kaiser, J

AU - Pezzilli, R

AU - Federici, F

AU - Mohelnikova-Duchonova, B

AU - Boggi, U

AU - Lemstrova, R

AU - Johansen, J S

AU - Bojesen, S E

AU - Chen, I

AU - Jensen, B V

AU - Capurso, G

AU - Pazienza, V

AU - Dervenis, C

AU - Sperti, C

AU - Mambrini, A

AU - Hackert, T

AU - Kaaks, R

AU - Basso, D

AU - Talar-Wojnarowska, R

AU - Maiello, E

AU - Izbicki, J R

AU - Cuk, K

AU - Saum, K U

AU - Cantore, M

AU - Kupcinskas, J

AU - Palmieri, O

AU - Delle Fave, G

AU - Landi, S

AU - Salvia, R

AU - Fogar, P

AU - Vashist, Y K

AU - Scarpa, A

AU - Vodicka, P

AU - Tjaden, C

AU - Iskierka-Jazdzewska, E

AU - Canzian, F

N1 - © 2019 UICC.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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 (OR dom) = 1.78, 95% confidence interval (CI) = 1.26–2.52, p = 1.19 × 10 −3 and OR dom = 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.

AB - 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 (OR dom) = 1.78, 95% confidence interval (CI) = 1.26–2.52, p = 1.19 × 10 −3 and OR dom = 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.

KW - Aged

KW - BRCA2 Protein/genetics

KW - Carcinoma, Pancreatic Ductal/genetics

KW - Case-Control Studies

KW - Checkpoint Kinase 2/genetics

KW - Female

KW - Genes, BRCA2

KW - Genetic Predisposition to Disease

KW - Germ-Line Mutation

KW - Humans

KW - Male

KW - Middle Aged

KW - Pancreatic Neoplasms/genetics

KW - Polymorphism, Single Nucleotide

UR - http://www.scopus.com/inward/record.url?scp=85061243831&partnerID=8YFLogxK

U2 - 10.1002/ijc.32127

DO - 10.1002/ijc.32127

M3 - Journal article

VL - 145

SP - 686

EP - 693

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 3

ER -

ID: 56638170