The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients

R Fagerholm; MK (Marjanka) Schmidt; Salima Khan; S Rafiq; W Tapper; K Aittomaki; D Greco; T Heikkinen; TA Muranen; PA Fasching; W Janni; R Weinshilboum; CR Loehberg; JL Hopper; MC Southey; R Keeman; A Lindblom; S Margolin; A Mannermaa; V Kataja; G Chenevix-Trench; D Lambrechts; H Wildiers; J Chang-Claude; P Seibold; FJ Couch; JE Olson; IL Andrulis; JA Knight; M Garcia-Closas; J Figueroa; Maartje Hooning; Agnes Jager; M Shah; BJ Perkins; R Luben; U Hamann; M Kabisch; K Czene; P Hall; DF Easton; PDP Pharoah; JJ Liu; D Eccles; C Blomqvist; H Nevanlinna

The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients

R Fagerholm
, MK (Marjanka) Schmidt
, Salima Khan
, S Rafiq
, W Tapper
, K Aittomaki
, D Greco
, T Heikkinen
, TA Muranen
, PA Fasching
, W Janni
, R Weinshilboum
, CR Loehberg
, JL Hopper
, MC Southey
, R Keeman
, A Lindblom
, S Margolin
, A Mannermaa
, V Kataja

G Chenevix-Trench, D Lambrechts, H Wildiers, J Chang-Claude, P Seibold, FJ Couch, JE Olson, IL Andrulis, JA Knight, M Garcia-Closas, J Figueroa, Maartje Hooning, Agnes Jager, M Shah, BJ Perkins, R Luben, U Hamann, M Kabisch, K Czene, P Hall, DF Easton, PDP Pharoah, JJ Liu, D Eccles, C Blomqvist, H Nevanlinna

Research output: Contribution to journal › Article › Academic › peer-review

14 Citations (Scopus)

Abstract

We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p((adjusted))=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p((adjusted))=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p((interaction))=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.

Original language	Undefined/Unknown
Pages (from-to)	7390-7407
Number of pages	18
Journal	Oncotarget
Volume	6
Issue number	10
Publication status	Published - 2015

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research programs

EMC MM-03-86-01

Cite this

Fagerholm, R., Schmidt, MK., Khan, S., Rafiq, S., Tapper, W., Aittomaki, K., Greco, D., Heikkinen, T., Muranen, TA., Fasching, PA., Janni, W., Weinshilboum, R., Loehberg, CR., Hopper, JL., Southey, MC., Keeman, R., Lindblom, A., Margolin, S., Mannermaa, A., ... Nevanlinna, H. (2015). The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients. Oncotarget, 6(10), 7390-7407.

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title = "The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients",

abstract = "We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95\% C.I. 1.08-1.26, p=0.0001, p((adjusted))=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95\% C.I. 1.08-1.35, p=0.0010, p((adjusted))=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p((interaction))=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95\% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.",

author = "R Fagerholm and Schmidt, \{MK (Marjanka)\} and Salima Khan and S Rafiq and W Tapper and K Aittomaki and D Greco and T Heikkinen and TA Muranen and PA Fasching and W Janni and R Weinshilboum and CR Loehberg and JL Hopper and MC Southey and R Keeman and A Lindblom and S Margolin and A Mannermaa and V Kataja and G Chenevix-Trench and D Lambrechts and H Wildiers and J Chang-Claude and P Seibold and FJ Couch and JE Olson and IL Andrulis and JA Knight and M Garcia-Closas and J Figueroa and Maartje Hooning and Agnes Jager and M Shah and BJ Perkins and R Luben and U Hamann and M Kabisch and K Czene and P Hall and DF Easton and PDP Pharoah and JJ Liu and D Eccles and C Blomqvist and H Nevanlinna",

year = "2015",

language = "Undefined/Unknown",

volume = "6",

pages = "7390--7407",

journal = "Oncotarget",

issn = "1949-2553",

publisher = "Impact Journals LLC",

number = "10",

}

Fagerholm, R, Schmidt, MK, Khan, S, Rafiq, S, Tapper, W, Aittomaki, K, Greco, D, Heikkinen, T, Muranen, TA, Fasching, PA, Janni, W, Weinshilboum, R, Loehberg, CR, Hopper, JL, Southey, MC, Keeman, R, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Chenevix-Trench, G, Lambrechts, D, Wildiers, H, Chang-Claude, J, Seibold, P, Couch, FJ, Olson, JE, Andrulis, IL, Knight, JA, Garcia-Closas, M, Figueroa, J, Hooning, M , Jager, A, Shah, M, Perkins, BJ, Luben, R, Hamann, U, Kabisch, M, Czene, K, Hall, P, Easton, DF, Pharoah, PDP, Liu, JJ, Eccles, D, Blomqvist, C & Nevanlinna, H 2015, 'The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients', Oncotarget, vol. 6, no. 10, pp. 7390-7407.

TY - JOUR

T1 - The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients

AU - Fagerholm, R

AU - Schmidt, MK (Marjanka)

AU - Khan, Salima

AU - Rafiq, S

AU - Tapper, W

AU - Aittomaki, K

AU - Greco, D

AU - Heikkinen, T

AU - Muranen, TA

AU - Fasching, PA

AU - Janni, W

AU - Weinshilboum, R

AU - Loehberg, CR

AU - Hopper, JL

AU - Southey, MC

AU - Keeman, R

AU - Lindblom, A

AU - Margolin, S

AU - Mannermaa, A

AU - Kataja, V

AU - Chenevix-Trench, G

AU - Lambrechts, D

AU - Wildiers, H

AU - Chang-Claude, J

AU - Seibold, P

AU - Couch, FJ

AU - Olson, JE

AU - Andrulis, IL

AU - Knight, JA

AU - Garcia-Closas, M

AU - Figueroa, J

AU - Hooning, Maartje

AU - Jager, Agnes

AU - Shah, M

AU - Perkins, BJ

AU - Luben, R

AU - Hamann, U

AU - Kabisch, M

AU - Czene, K

AU - Hall, P

AU - Easton, DF

AU - Pharoah, PDP

AU - Liu, JJ

AU - Eccles, D

AU - Blomqvist, C

AU - Nevanlinna, H

PY - 2015

Y1 - 2015

N2 - We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p((adjusted))=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p((adjusted))=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p((interaction))=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.

AB - We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p((adjusted))=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p((adjusted))=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p((interaction))=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.

M3 - Article

SN - 1949-2553

VL - 6

SP - 7390

EP - 7407

JO - Oncotarget

JF - Oncotarget

IS - 10

ER -