Abstract
| Original language | Undefined/Unknown |
|---|---|
| Pages (from-to) | 6096-6111 |
| Number of pages | 16 |
| Journal | Human Molecular Genetics |
| Volume | 23 |
| Issue number | 22 |
| DOIs | |
| Publication status | Published - 2014 |
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Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium. / Milne, RL; Burwinkel, B; Michailidou, K; Arias-Perez, JI; Zamora, MP; Menendez-Rodriguez, P; Hardisson, D; Mendiola, M; Gonzalez-Neira, A; Pita, G; Alonso, MR; Dennis, J; Wang, Q (Qing); Bolla, MK; Swerdlow, A; Ashworth, A; Orr, N; Schoemaker, M; Ko, YD; Brauch, H; Hamann, U; Andrulis, IL; Knight, JA; Glendon, G; Tchatchou, S; Matsuo, K; Ito, H; Iwata, H; Tajima, K; Li, JM; Brand, JS; Brenner, H; Dieffenbach, AK; Arndt, V; Stegmaier, C; Lambrechts, D; Peuteman, G; Christiaens, MR; Smeets, A; Jakubowska, A; Lubinski, J; Jaworska-Bieniek, K; Durda, K; Hartman, M; Hui, M; Lim, WY; Chan, CW; Marme, F; Yang, RX; Bugert, P; Lindblom, A; Margolin, S; Garcia-Closas, M; Chanock, SJ; Lissowska, J; Figueroa, JD; Bojesen, SE; Nordestgaard, BG; Flyger, H; Hooning, Maartje; Kriege, Mieke; van den Ouweland, Ans; Koppert, Linetta; Fletcher, O; Johnson, N; dos-Santos-Silva, I; Peto, J; Zheng, W; Deming-Halverson, S; Shrubsole, MJ; Long, JR; Chang-Claude, J; Rudolph, A; Seibold, P; Flesch-Janys, D; Winqvist, R; Pylkas, K; Jukkola-Vuorinen, A; Grip, M; Cox, A; Cross, SS; Reed, MWR; Schmidt, MK (Marjanka); Broeks, A; Cornelissen, S; Braaf, L; Kang, D; Choi, JY; Park, SK; Noh, DY; Simard, J; Dumont, M; Goldberg, MS; Labreche, F; Fasching, PA; Hein, A; Ekici, AB; Beckmann, MW; Radice, P; Peterlongo, P; Azzollini, J; Barile, M; Sawyer, E; Tomlinson, I; Kerin, M; Miller, N; Hopper, JL; Schmidt, DF; Makalic, E; Southey, MC; Teo, SH; Yip, CH; Sivanandan, K; Tay, WT; Shen, CY; Hsiung, CN; Yu, JC; Hou, MF; Guenel, P; Sanchez, M; Mulot, C; Blot, W; Cai, QY; Nevanlinna, H; Muranen, TA; Aittomaki, K; Blomqvist, C; Wu, AH; Tseng, CC; van den Berg, D; Stram, DO; Bogdanova, N; Dork, T; Muir, K; Lophatananon, A; Stewart-Brown, S; Siriwanarangsan, P; Mannermaa, A; Kataja, V; Kosma, VM; Hartikainen, JM; Shu, XO; Lu, W; Gao, YT; Zhang, B; Couch, FJ; Toland, AE; Yannoukakos, D; Sangrajrang, S; Mckay, J; Wang, XS; Olson, JE; Vachon, C; Purrington, K; Severi, G; Baglietto, L; Haiman, CA; Henderson, BE; Schumacher, F; Le Marchand, L; Devilee, P; Tollenaar, RAEM; Seynaeve, Caroline; Czene, K; Eriksson, M; Humphreys, K; Darabi, H; Ahmed, S (Shahana); Shah, M; Pharoah, PDP; Hall, P; Giles, GG; Benitez, J; Dunning, AM; Chenevix-Trench, G; Easton, DF.
In: Human Molecular Genetics, Vol. 23, No. 22, 2014, p. 6096-6111.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium
AU - Milne, RL
AU - Burwinkel, B
AU - Michailidou, K
AU - Arias-Perez, JI
AU - Zamora, MP
AU - Menendez-Rodriguez, P
AU - Hardisson, D
AU - Mendiola, M
AU - Gonzalez-Neira, A
AU - Pita, G
AU - Alonso, MR
AU - Dennis, J
AU - Wang, Q (Qing)
AU - Bolla, MK
AU - Swerdlow, A
AU - Ashworth, A
AU - Orr, N
AU - Schoemaker, M
AU - Ko, YD
AU - Brauch, H
AU - Hamann, U
AU - Andrulis, IL
AU - Knight, JA
AU - Glendon, G
AU - Tchatchou, S
AU - Matsuo, K
AU - Ito, H
AU - Iwata, H
AU - Tajima, K
AU - Li, JM
AU - Brand, JS
AU - Brenner, H
AU - Dieffenbach, AK
AU - Arndt, V
AU - Stegmaier, C
AU - Lambrechts, D
AU - Peuteman, G
AU - Christiaens, MR
AU - Smeets, A
AU - Jakubowska, A
AU - Lubinski, J
AU - Jaworska-Bieniek, K
AU - Durda, K
AU - Hartman, M
AU - Hui, M
AU - Lim, WY
AU - Chan, CW
AU - Marme, F
AU - Yang, RX
AU - Bugert, P
AU - Lindblom, A
AU - Margolin, S
AU - Garcia-Closas, M
AU - Chanock, SJ
AU - Lissowska, J
AU - Figueroa, JD
AU - Bojesen, SE
AU - Nordestgaard, BG
AU - Flyger, H
AU - Hooning, Maartje
AU - Kriege, Mieke
AU - van den Ouweland, Ans
AU - Koppert, Linetta
AU - Fletcher, O
AU - Johnson, N
AU - dos-Santos-Silva, I
AU - Peto, J
AU - Zheng, W
AU - Deming-Halverson, S
AU - Shrubsole, MJ
AU - Long, JR
AU - Chang-Claude, J
AU - Rudolph, A
AU - Seibold, P
AU - Flesch-Janys, D
AU - Winqvist, R
AU - Pylkas, K
AU - Jukkola-Vuorinen, A
AU - Grip, M
AU - Cox, A
AU - Cross, SS
AU - Reed, MWR
AU - Schmidt, MK (Marjanka)
AU - Broeks, A
AU - Cornelissen, S
AU - Braaf, L
AU - Kang, D
AU - Choi, JY
AU - Park, SK
AU - Noh, DY
AU - Simard, J
AU - Dumont, M
AU - Goldberg, MS
AU - Labreche, F
AU - Fasching, PA
AU - Hein, A
AU - Ekici, AB
AU - Beckmann, MW
AU - Radice, P
AU - Peterlongo, P
AU - Azzollini, J
AU - Barile, M
AU - Sawyer, E
AU - Tomlinson, I
AU - Kerin, M
AU - Miller, N
AU - Hopper, JL
AU - Schmidt, DF
AU - Makalic, E
AU - Southey, MC
AU - Teo, SH
AU - Yip, CH
AU - Sivanandan, K
AU - Tay, WT
AU - Shen, CY
AU - Hsiung, CN
AU - Yu, JC
AU - Hou, MF
AU - Guenel, P
AU - Sanchez, M
AU - Mulot, C
AU - Blot, W
AU - Cai, QY
AU - Nevanlinna, H
AU - Muranen, TA
AU - Aittomaki, K
AU - Blomqvist, C
AU - Wu, AH
AU - Tseng, CC
AU - van den Berg, D
AU - Stram, DO
AU - Bogdanova, N
AU - Dork, T
AU - Muir, K
AU - Lophatananon, A
AU - Stewart-Brown, S
AU - Siriwanarangsan, P
AU - Mannermaa, A
AU - Kataja, V
AU - Kosma, VM
AU - Hartikainen, JM
AU - Shu, XO
AU - Lu, W
AU - Gao, YT
AU - Zhang, B
AU - Couch, FJ
AU - Toland, AE
AU - Yannoukakos, D
AU - Sangrajrang, S
AU - Mckay, J
AU - Wang, XS
AU - Olson, JE
AU - Vachon, C
AU - Purrington, K
AU - Severi, G
AU - Baglietto, L
AU - Haiman, CA
AU - Henderson, BE
AU - Schumacher, F
AU - Le Marchand, L
AU - Devilee, P
AU - Tollenaar, RAEM
AU - Seynaeve, Caroline
AU - Czene, K
AU - Eriksson, M
AU - Humphreys, K
AU - Darabi, H
AU - Ahmed, S (Shahana)
AU - Shah, M
AU - Pharoah, PDP
AU - Hall, P
AU - Giles, GG
AU - Benitez, J
AU - Dunning, AM
AU - Chenevix-Trench, G
AU - Easton, DF
PY - 2014
Y1 - 2014
N2 - Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 x 10 26], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 x 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 x 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 x 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 x 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.
AB - Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 x 10 26], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 x 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 x 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 x 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 x 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.
U2 - 10.1093/hmg/ddu311
DO - 10.1093/hmg/ddu311
M3 - Article
VL - 23
SP - 6096
EP - 6111
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 22
ER -