Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium

Jieping Lei; Anja Rudolph; Kirsten B Moysich; Sabine Behrens; Ellen L Goode; Manjeet K Bolla; Joe Dennis; Alison M Dunning; Douglas F Easton; Qin Wang; Javier Benitez; John L Hopper; Melissa C Southey; Marjanka K Schmidt; Annegien Broeks; Peter A Fasching; Lothar Haeberle; Julian Peto; Isabel Dos-Santos-Silva; Elinor J Sawyer; Ian Tomlinson; Barbara Burwinkel; Frederik Marmé; Pascal Guénel; Thérèse Truong; Stig E Bojesen; Henrik Flyger; Sune F Nielsen; Børge G Nordestgaard; Anna González-Neira; Primitiva Menéndez; Hoda Anton-Culver; Susan L Neuhausen; Hermann Brenner; Volker Arndt; Alfons Meindl; Rita K Schmutzler; Hiltrud Brauch; Ute Hamann; Heli Nevanlinna; Rainer Fagerholm; Thilo Dörk; Natalia V Bogdanova; Arto Mannermaa; Jaana M Hartikainen; Laurien Van Dijck; Ann Smeets; Dieter Flesch-Janys; Ursula Eilber; Paolo Radice; Australian Ovarian Study Group

doi:10.1007/s00439-015-1616-8

Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium

Jieping Lei, Anja Rudolph, Kirsten B Moysich, Sabine Behrens, Ellen L Goode, Manjeet K Bolla, Joe Dennis, Alison M Dunning, Douglas F Easton, Qin Wang, Javier Benitez, John L Hopper, Melissa C Southey, Marjanka K Schmidt, Annegien Broeks, Peter A Fasching, Lothar Haeberle, Julian Peto, Isabel Dos-Santos-Silva, Elinor J SawyerIan Tomlinson, Barbara Burwinkel, Frederik Marmé, Pascal Guénel, Thérèse Truong, Stig E Bojesen, Henrik Flyger, Sune F Nielsen, Børge G Nordestgaard, Anna González-Neira, Primitiva Menéndez, Hoda Anton-Culver, Susan L Neuhausen, Hermann Brenner, Volker Arndt, Alfons Meindl, Rita K Schmutzler, Hiltrud Brauch, Ute Hamann, Heli Nevanlinna, Rainer Fagerholm, Thilo Dörk, Natalia V Bogdanova, Arto Mannermaa, Jaana M Hartikainen, Laurien Van Dijck, Ann Smeets, Dieter Flesch-Janys, Ursula Eilber, Paolo Radice, Australian Ovarian Study Group

Institut for Klinisk Medicin

7 Citationer (Scopus)

Abstract

Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 × 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10(-3), 4.5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry.

Originalsprog	Engelsk
Tidsskrift	Human Genetics
Vol/bind	135
Udgave nummer	1
Sider (fra-til)	137-54
Antal sider	18
ISSN	0340-6717
DOI	https://doi.org/10.1007/s00439-015-1616-8
Status	Udgivet - 1 jan. 2016

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10.1007/s00439-015-1616-8

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Lei, J., Rudolph, A., Moysich, K. B., Behrens, S., Goode, E. L., Bolla, M. K., Dennis, J., Dunning, A. M., Easton, D. F., Wang, Q., Benitez, J., Hopper, J. L., Southey, M. C., Schmidt, M. K., Broeks, A., Fasching, P. A., Haeberle, L., Peto, J., Dos-Santos-Silva, I., ... Australian Ovarian Study Group (2016). Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium. Human Genetics, 135(1), 137-54. https://doi.org/10.1007/s00439-015-1616-8

Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium. / Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B et al.
I: Human Genetics, Bind 135, Nr. 1, 01.01.2016, s. 137-54.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Lei, J, Rudolph, A, Moysich, KB, Behrens, S, Goode, EL, Bolla, MK, Dennis, J, Dunning, AM, Easton, DF, Wang, Q, Benitez, J, Hopper, JL, Southey, MC, Schmidt, MK, Broeks, A, Fasching, PA, Haeberle, L, Peto, J, Dos-Santos-Silva, I, Sawyer, EJ, Tomlinson, I, Burwinkel, B, Marmé, F, Guénel, P, Truong, T, Bojesen, SE, Flyger, H, Nielsen, SF, Nordestgaard, BG, González-Neira, A, Menéndez, P, Anton-Culver, H, Neuhausen, SL, Brenner, H, Arndt, V, Meindl, A, Schmutzler, RK, Brauch, H, Hamann, U, Nevanlinna, H, Fagerholm, R, Dörk, T, Bogdanova, NV, Mannermaa, A, Hartikainen, JM, Van Dijck, L, Smeets, A, Flesch-Janys, D, Eilber, U, Radice, P & Australian Ovarian Study Group 2016, 'Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium', Human Genetics, bind 135, nr. 1, s. 137-54. https://doi.org/10.1007/s00439-015-1616-8

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title = "Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium",

abstract = "Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 × 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10(-3), 4.5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry.",

author = "Jieping Lei and Anja Rudolph and Moysich, {Kirsten B} and Sabine Behrens and Goode, {Ellen L} and Bolla, {Manjeet K} and Joe Dennis and Dunning, {Alison M} and Easton, {Douglas F} and Qin Wang and Javier Benitez and Hopper, {John L} and Southey, {Melissa C} and Schmidt, {Marjanka K} and Annegien Broeks and Fasching, {Peter A} and Lothar Haeberle and Julian Peto and Isabel Dos-Santos-Silva and Sawyer, {Elinor J} and Ian Tomlinson and Barbara Burwinkel and Frederik Marm{\'e} and Pascal Gu{\'e}nel and Th{\'e}r{\`e}se Truong and Bojesen, {Stig E} and Henrik Flyger and Nielsen, {Sune F} and Nordestgaard, {B{\o}rge G} and Anna Gonz{\'a}lez-Neira and Primitiva Men{\'e}ndez and Hoda Anton-Culver and Neuhausen, {Susan L} and Hermann Brenner and Volker Arndt and Alfons Meindl and Schmutzler, {Rita K} and Hiltrud Brauch and Ute Hamann and Heli Nevanlinna and Rainer Fagerholm and Thilo D{\"o}rk and Bogdanova, {Natalia V} and Arto Mannermaa and Hartikainen, {Jaana M} and {Van Dijck}, Laurien and Ann Smeets and Dieter Flesch-Janys and Ursula Eilber and Paolo Radice and {Australian Ovarian Study Group}",

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doi = "10.1007/s00439-015-1616-8",

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T1 - Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility

T2 - a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium

AU - Lei, Jieping

AU - Rudolph, Anja

AU - Moysich, Kirsten B

AU - Behrens, Sabine

AU - Goode, Ellen L

AU - Bolla, Manjeet K

AU - Dennis, Joe

AU - Dunning, Alison M

AU - Easton, Douglas F

AU - Wang, Qin

AU - Benitez, Javier

AU - Hopper, John L

AU - Southey, Melissa C

AU - Schmidt, Marjanka K

AU - Broeks, Annegien

AU - Fasching, Peter A

AU - Haeberle, Lothar

AU - Peto, Julian

AU - Dos-Santos-Silva, Isabel

AU - Sawyer, Elinor J

AU - Tomlinson, Ian

AU - Burwinkel, Barbara

AU - Marmé, Frederik

AU - Guénel, Pascal

AU - Truong, Thérèse

AU - Bojesen, Stig E

AU - Flyger, Henrik

AU - Nielsen, Sune F

AU - Nordestgaard, Børge G

AU - González-Neira, Anna

AU - Menéndez, Primitiva

AU - Anton-Culver, Hoda

AU - Neuhausen, Susan L

AU - Brenner, Hermann

AU - Arndt, Volker

AU - Meindl, Alfons

AU - Schmutzler, Rita K

AU - Brauch, Hiltrud

AU - Hamann, Ute

AU - Nevanlinna, Heli

AU - Fagerholm, Rainer

AU - Dörk, Thilo

AU - Bogdanova, Natalia V

AU - Mannermaa, Arto

AU - Hartikainen, Jaana M

AU - Van Dijck, Laurien

AU - Smeets, Ann

AU - Flesch-Janys, Dieter

AU - Eilber, Ursula

AU - Radice, Paolo

AU - Australian Ovarian Study Group

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 × 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10(-3), 4.5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry.

AB - Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 × 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10(-3), 4.5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry.

U2 - 10.1007/s00439-015-1616-8

DO - 10.1007/s00439-015-1616-8

M3 - Journal article

C2 - 26621531

SN - 0340-6717

VL - 135

SP - 137

EP - 154

JO - Human Genetics

JF - Human Genetics

IS - 1

ER -

Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium

Abstract

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