Risk of estrogen receptor-positive and -negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042

Roger L. Milne, Javier Benítez, Heli Nevanlinna, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, José Ignacio Arias, M. Pilar Zamora, Barbara Burwinkel, Claus R. Bartram, Alfons Meindl, Rita K. Schmutzler, Angela Cox, Ian Brock, Graeme Elliott, Malcolm W R Reed, Melissa C. Southey, Letitia Smith, Amanda B. Spurdle, John L. Hopper & 73 others Fergus J. Couch, Janet E. Olson, Xianshu Wang, Zachary Fredericksen, Peter Schürmann, Michael Bremer, Peter Hillemanns, Thilo Dörk, Peter Devilee, Christie J. Van Asperen, Rob A E M Tollenaar, Caroline Seynaeve, Per Hall, Kamila Czene, Jianjun Liu, Yuqing Li, Shahana Ahmed, Alison M. Dunning, Melanie Maranian, Paul D P Pharoah, Georgia Chenevix-Trench, Jonathan Beesley, Natalia V. Bogdanova, Natalia N. Antonenkova, Iosif V. Zalutsky, Hoda Anton-Culver, Argyrios Ziogas, Hiltrud Brauch, Christina Justenhoven, Yon Dschun Ko, Susanne Haas, Peter A. Fasching, Reiner Strick, Arif B. Ekici, Matthias W. Beckmann, Graham G. Giles, Gianluca Severi, Laura Baglietto, Dallas R. English, Olivia Fletcher, Nichola Johnson, Isabel Dos Santos Silva, Julian Peto, Clare Turnbull, Sarah Hines, Anthony Renwick, Nazneen Rahman, Børge G. Nordestgaard, Stig E. Bojesen, Henrik Flyger, Daehee Kang, Keun Young Yoo, Dong Young Noh, Arto Mannermaa, Vesa Kataja, Veli Matti Kosma, Montserrat García-Closas, Stephen Chanock, Jolanta Lissowska, Louise A. Brinton, Jenny Chang-Claude, Shan Wang-Gohrke, Chen Yang Shen, Hui Chun Wang, Jyh Cherng Yu, Sou Tong Chen, Marina Bermisheva, Tatjana Nikolaeva, Elza Khusnutdinova, Manjeet K. Humphreys, Jonathan Morrison, Radka Platte, Douglas F. Easton

Research output: Contribution to journalArticle

Abstract

BackgroundA recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium.Methods2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided.ResultsWe found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95% confidence interval [CI] = 1.09 to 1.15; Ptrend = 1.0 × 10 -19). The odds ratio was lower than that previously reported (P =. 02) and did not vary by age or ethnicity (all P ≥. 2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95% CI = 1.10 to 1.17; P = 10 -15) and ER-negative disease (OR = 1.10, 95% CI = 1.04 to 1.15; P =. 0003) and both progesterone receptor (PR)-positive (OR = 1.15, 95% CI = 1.11 to 1.19; P = 5 × 10 -14) and PR-negative disease (OR = 1.10, 95% CI = 1.06 to 1.15; P =. 00002).ConclusionThe rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women.

Original languageEnglish (US)
Pages (from-to)1012-1018
Number of pages7
JournalJournal of the National Cancer Institute
Volume101
Issue number14
DOIs
StatePublished - Jul 2009
Externally publishedYes

Fingerprint

Estrogen Receptors
Single Nucleotide Polymorphism
Odds Ratio
Breast Neoplasms
Confidence Intervals
Progesterone Receptors
Logistic Models
Carcinoma, Intraductal, Noninfiltrating
Genome-Wide Association Study
Alleles
Hormones

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Milne, R. L., Benítez, J., Nevanlinna, H., Heikkinen, T., Aittomäki, K., Blomqvist, C., ... Easton, D. F. (2009). Risk of estrogen receptor-positive and -negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042. Journal of the National Cancer Institute, 101(14), 1012-1018. https://doi.org/10.1093/jnci/djp167

Risk of estrogen receptor-positive and -negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042. / Milne, Roger L.; Benítez, Javier; Nevanlinna, Heli; Heikkinen, Tuomas; Aittomäki, Kristiina; Blomqvist, Carl; Arias, José Ignacio; Zamora, M. Pilar; Burwinkel, Barbara; Bartram, Claus R.; Meindl, Alfons; Schmutzler, Rita K.; Cox, Angela; Brock, Ian; Elliott, Graeme; Reed, Malcolm W R; Southey, Melissa C.; Smith, Letitia; Spurdle, Amanda B.; Hopper, John L.; Couch, Fergus J.; Olson, Janet E.; Wang, Xianshu; Fredericksen, Zachary; Schürmann, Peter; Bremer, Michael; Hillemanns, Peter; Dörk, Thilo; Devilee, Peter; Van Asperen, Christie J.; Tollenaar, Rob A E M; Seynaeve, Caroline; Hall, Per; Czene, Kamila; Liu, Jianjun; Li, Yuqing; Ahmed, Shahana; Dunning, Alison M.; Maranian, Melanie; Pharoah, Paul D P; Chenevix-Trench, Georgia; Beesley, Jonathan; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Zalutsky, Iosif V.; Anton-Culver, Hoda; Ziogas, Argyrios; Brauch, Hiltrud; Justenhoven, Christina; Ko, Yon Dschun; Haas, Susanne; Fasching, Peter A.; Strick, Reiner; Ekici, Arif B.; Beckmann, Matthias W.; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; English, Dallas R.; Fletcher, Olivia; Johnson, Nichola; Dos Santos Silva, Isabel; Peto, Julian; Turnbull, Clare; Hines, Sarah; Renwick, Anthony; Rahman, Nazneen; Nordestgaard, Børge G.; Bojesen, Stig E.; Flyger, Henrik; Kang, Daehee; Yoo, Keun Young; Noh, Dong Young; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli Matti; García-Closas, Montserrat; Chanock, Stephen; Lissowska, Jolanta; Brinton, Louise A.; Chang-Claude, Jenny; Wang-Gohrke, Shan; Shen, Chen Yang; Wang, Hui Chun; Yu, Jyh Cherng; Chen, Sou Tong; Bermisheva, Marina; Nikolaeva, Tatjana; Khusnutdinova, Elza; Humphreys, Manjeet K.; Morrison, Jonathan; Platte, Radka; Easton, Douglas F.

In: Journal of the National Cancer Institute, Vol. 101, No. 14, 07.2009, p. 1012-1018.

Research output: Contribution to journalArticle

Milne, RL, Benítez, J, Nevanlinna, H, Heikkinen, T, Aittomäki, K, Blomqvist, C, Arias, JI, Zamora, MP, Burwinkel, B, Bartram, CR, Meindl, A, Schmutzler, RK, Cox, A, Brock, I, Elliott, G, Reed, MWR, Southey, MC, Smith, L, Spurdle, AB, Hopper, JL, Couch, FJ, Olson, JE, Wang, X, Fredericksen, Z, Schürmann, P, Bremer, M, Hillemanns, P, Dörk, T, Devilee, P, Van Asperen, CJ, Tollenaar, RAEM, Seynaeve, C, Hall, P, Czene, K, Liu, J, Li, Y, Ahmed, S, Dunning, AM, Maranian, M, Pharoah, PDP, Chenevix-Trench, G, Beesley, J, Bogdanova, NV, Antonenkova, NN, Zalutsky, IV, Anton-Culver, H, Ziogas, A, Brauch, H, Justenhoven, C, Ko, YD, Haas, S, Fasching, PA, Strick, R, Ekici, AB, Beckmann, MW, Giles, GG, Severi, G, Baglietto, L, English, DR, Fletcher, O, Johnson, N, Dos Santos Silva, I, Peto, J, Turnbull, C, Hines, S, Renwick, A, Rahman, N, Nordestgaard, BG, Bojesen, SE, Flyger, H, Kang, D, Yoo, KY, Noh, DY, Mannermaa, A, Kataja, V, Kosma, VM, García-Closas, M, Chanock, S, Lissowska, J, Brinton, LA, Chang-Claude, J, Wang-Gohrke, S, Shen, CY, Wang, HC, Yu, JC, Chen, ST, Bermisheva, M, Nikolaeva, T, Khusnutdinova, E, Humphreys, MK, Morrison, J, Platte, R & Easton, DF 2009, 'Risk of estrogen receptor-positive and -negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042', Journal of the National Cancer Institute, vol. 101, no. 14, pp. 1012-1018. https://doi.org/10.1093/jnci/djp167
Milne, Roger L. ; Benítez, Javier ; Nevanlinna, Heli ; Heikkinen, Tuomas ; Aittomäki, Kristiina ; Blomqvist, Carl ; Arias, José Ignacio ; Zamora, M. Pilar ; Burwinkel, Barbara ; Bartram, Claus R. ; Meindl, Alfons ; Schmutzler, Rita K. ; Cox, Angela ; Brock, Ian ; Elliott, Graeme ; Reed, Malcolm W R ; Southey, Melissa C. ; Smith, Letitia ; Spurdle, Amanda B. ; Hopper, John L. ; Couch, Fergus J. ; Olson, Janet E. ; Wang, Xianshu ; Fredericksen, Zachary ; Schürmann, Peter ; Bremer, Michael ; Hillemanns, Peter ; Dörk, Thilo ; Devilee, Peter ; Van Asperen, Christie J. ; Tollenaar, Rob A E M ; Seynaeve, Caroline ; Hall, Per ; Czene, Kamila ; Liu, Jianjun ; Li, Yuqing ; Ahmed, Shahana ; Dunning, Alison M. ; Maranian, Melanie ; Pharoah, Paul D P ; Chenevix-Trench, Georgia ; Beesley, Jonathan ; Bogdanova, Natalia V. ; Antonenkova, Natalia N. ; Zalutsky, Iosif V. ; Anton-Culver, Hoda ; Ziogas, Argyrios ; Brauch, Hiltrud ; Justenhoven, Christina ; Ko, Yon Dschun ; Haas, Susanne ; Fasching, Peter A. ; Strick, Reiner ; Ekici, Arif B. ; Beckmann, Matthias W. ; Giles, Graham G. ; Severi, Gianluca ; Baglietto, Laura ; English, Dallas R. ; Fletcher, Olivia ; Johnson, Nichola ; Dos Santos Silva, Isabel ; Peto, Julian ; Turnbull, Clare ; Hines, Sarah ; Renwick, Anthony ; Rahman, Nazneen ; Nordestgaard, Børge G. ; Bojesen, Stig E. ; Flyger, Henrik ; Kang, Daehee ; Yoo, Keun Young ; Noh, Dong Young ; Mannermaa, Arto ; Kataja, Vesa ; Kosma, Veli Matti ; García-Closas, Montserrat ; Chanock, Stephen ; Lissowska, Jolanta ; Brinton, Louise A. ; Chang-Claude, Jenny ; Wang-Gohrke, Shan ; Shen, Chen Yang ; Wang, Hui Chun ; Yu, Jyh Cherng ; Chen, Sou Tong ; Bermisheva, Marina ; Nikolaeva, Tatjana ; Khusnutdinova, Elza ; Humphreys, Manjeet K. ; Morrison, Jonathan ; Platte, Radka ; Easton, Douglas F. / Risk of estrogen receptor-positive and -negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042. In: Journal of the National Cancer Institute. 2009 ; Vol. 101, No. 14. pp. 1012-1018.
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title = "Risk of estrogen receptor-positive and -negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042",
abstract = "BackgroundA recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium.Methods2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided.ResultsWe found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95{\%} confidence interval [CI] = 1.09 to 1.15; Ptrend = 1.0 × 10 -19). The odds ratio was lower than that previously reported (P =. 02) and did not vary by age or ethnicity (all P ≥. 2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95{\%} CI = 1.10 to 1.17; P = 10 -15) and ER-negative disease (OR = 1.10, 95{\%} CI = 1.04 to 1.15; P =. 0003) and both progesterone receptor (PR)-positive (OR = 1.15, 95{\%} CI = 1.11 to 1.19; P = 5 × 10 -14) and PR-negative disease (OR = 1.10, 95{\%} CI = 1.06 to 1.15; P =. 00002).ConclusionThe rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women.",
author = "Milne, {Roger L.} and Javier Ben{\'i}tez and Heli Nevanlinna and Tuomas Heikkinen and Kristiina Aittom{\"a}ki and Carl Blomqvist and Arias, {Jos{\'e} Ignacio} and Zamora, {M. Pilar} and Barbara Burwinkel and Bartram, {Claus R.} and Alfons Meindl and Schmutzler, {Rita K.} and Angela Cox and Ian Brock and Graeme Elliott and Reed, {Malcolm W R} and Southey, {Melissa C.} and Letitia Smith and Spurdle, {Amanda B.} and Hopper, {John L.} and Couch, {Fergus J.} and Olson, {Janet E.} and Xianshu Wang and Zachary Fredericksen and Peter Sch{\"u}rmann and Michael Bremer and Peter Hillemanns and Thilo D{\"o}rk and Peter Devilee and {Van Asperen}, {Christie J.} and Tollenaar, {Rob A E M} and Caroline Seynaeve and Per Hall and Kamila Czene and Jianjun Liu and Yuqing Li and Shahana Ahmed and Dunning, {Alison M.} and Melanie Maranian and Pharoah, {Paul D P} and Georgia Chenevix-Trench and Jonathan Beesley and Bogdanova, {Natalia V.} and Antonenkova, {Natalia N.} and Zalutsky, {Iosif V.} and Hoda Anton-Culver and Argyrios Ziogas and Hiltrud Brauch and Christina Justenhoven and Ko, {Yon Dschun} and Susanne Haas and Fasching, {Peter A.} and Reiner Strick and Ekici, {Arif B.} and Beckmann, {Matthias W.} and Giles, {Graham G.} and Gianluca Severi and Laura Baglietto and English, {Dallas R.} and Olivia Fletcher and Nichola Johnson and {Dos Santos Silva}, Isabel and Julian Peto and Clare Turnbull and Sarah Hines and Anthony Renwick and Nazneen Rahman and Nordestgaard, {B{\o}rge G.} and Bojesen, {Stig E.} and Henrik Flyger and Daehee Kang and Yoo, {Keun Young} and Noh, {Dong Young} and Arto Mannermaa and Vesa Kataja and Kosma, {Veli Matti} and Montserrat Garc{\'i}a-Closas and Stephen Chanock and Jolanta Lissowska and Brinton, {Louise A.} and Jenny Chang-Claude and Shan Wang-Gohrke and Shen, {Chen Yang} and Wang, {Hui Chun} and Yu, {Jyh Cherng} and Chen, {Sou Tong} and Marina Bermisheva and Tatjana Nikolaeva and Elza Khusnutdinova and Humphreys, {Manjeet K.} and Jonathan Morrison and Radka Platte and Easton, {Douglas F.}",
year = "2009",
month = "7",
doi = "10.1093/jnci/djp167",
language = "English (US)",
volume = "101",
pages = "1012--1018",
journal = "Journal of the National Cancer Institute",
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TY - JOUR

T1 - Risk of estrogen receptor-positive and -negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042

AU - Milne, Roger L.

AU - Benítez, Javier

AU - Nevanlinna, Heli

AU - Heikkinen, Tuomas

AU - Aittomäki, Kristiina

AU - Blomqvist, Carl

AU - Arias, José Ignacio

AU - Zamora, M. Pilar

AU - Burwinkel, Barbara

AU - Bartram, Claus R.

AU - Meindl, Alfons

AU - Schmutzler, Rita K.

AU - Cox, Angela

AU - Brock, Ian

AU - Elliott, Graeme

AU - Reed, Malcolm W R

AU - Southey, Melissa C.

AU - Smith, Letitia

AU - Spurdle, Amanda B.

AU - Hopper, John L.

AU - Couch, Fergus J.

AU - Olson, Janet E.

AU - Wang, Xianshu

AU - Fredericksen, Zachary

AU - Schürmann, Peter

AU - Bremer, Michael

AU - Hillemanns, Peter

AU - Dörk, Thilo

AU - Devilee, Peter

AU - Van Asperen, Christie J.

AU - Tollenaar, Rob A E M

AU - Seynaeve, Caroline

AU - Hall, Per

AU - Czene, Kamila

AU - Liu, Jianjun

AU - Li, Yuqing

AU - Ahmed, Shahana

AU - Dunning, Alison M.

AU - Maranian, Melanie

AU - Pharoah, Paul D P

AU - Chenevix-Trench, Georgia

AU - Beesley, Jonathan

AU - Bogdanova, Natalia V.

AU - Antonenkova, Natalia N.

AU - Zalutsky, Iosif V.

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Brauch, Hiltrud

AU - Justenhoven, Christina

AU - Ko, Yon Dschun

AU - Haas, Susanne

AU - Fasching, Peter A.

AU - Strick, Reiner

AU - Ekici, Arif B.

AU - Beckmann, Matthias W.

AU - Giles, Graham G.

AU - Severi, Gianluca

AU - Baglietto, Laura

AU - English, Dallas R.

AU - Fletcher, Olivia

AU - Johnson, Nichola

AU - Dos Santos Silva, Isabel

AU - Peto, Julian

AU - Turnbull, Clare

AU - Hines, Sarah

AU - Renwick, Anthony

AU - Rahman, Nazneen

AU - Nordestgaard, Børge G.

AU - Bojesen, Stig E.

AU - Flyger, Henrik

AU - Kang, Daehee

AU - Yoo, Keun Young

AU - Noh, Dong Young

AU - Mannermaa, Arto

AU - Kataja, Vesa

AU - Kosma, Veli Matti

AU - García-Closas, Montserrat

AU - Chanock, Stephen

AU - Lissowska, Jolanta

AU - Brinton, Louise A.

AU - Chang-Claude, Jenny

AU - Wang-Gohrke, Shan

AU - Shen, Chen Yang

AU - Wang, Hui Chun

AU - Yu, Jyh Cherng

AU - Chen, Sou Tong

AU - Bermisheva, Marina

AU - Nikolaeva, Tatjana

AU - Khusnutdinova, Elza

AU - Humphreys, Manjeet K.

AU - Morrison, Jonathan

AU - Platte, Radka

AU - Easton, Douglas F.

PY - 2009/7

Y1 - 2009/7

N2 - BackgroundA recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium.Methods2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided.ResultsWe found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95% confidence interval [CI] = 1.09 to 1.15; Ptrend = 1.0 × 10 -19). The odds ratio was lower than that previously reported (P =. 02) and did not vary by age or ethnicity (all P ≥. 2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95% CI = 1.10 to 1.17; P = 10 -15) and ER-negative disease (OR = 1.10, 95% CI = 1.04 to 1.15; P =. 0003) and both progesterone receptor (PR)-positive (OR = 1.15, 95% CI = 1.11 to 1.19; P = 5 × 10 -14) and PR-negative disease (OR = 1.10, 95% CI = 1.06 to 1.15; P =. 00002).ConclusionThe rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women.

AB - BackgroundA recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium.Methods2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided.ResultsWe found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95% confidence interval [CI] = 1.09 to 1.15; Ptrend = 1.0 × 10 -19). The odds ratio was lower than that previously reported (P =. 02) and did not vary by age or ethnicity (all P ≥. 2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95% CI = 1.10 to 1.17; P = 10 -15) and ER-negative disease (OR = 1.10, 95% CI = 1.04 to 1.15; P =. 0003) and both progesterone receptor (PR)-positive (OR = 1.15, 95% CI = 1.11 to 1.19; P = 5 × 10 -14) and PR-negative disease (OR = 1.10, 95% CI = 1.06 to 1.15; P =. 00002).ConclusionThe rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women.

UR - http://www.scopus.com/inward/record.url?scp=67650825015&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650825015&partnerID=8YFLogxK

U2 - 10.1093/jnci/djp167

DO - 10.1093/jnci/djp167

M3 - Article

VL - 101

SP - 1012

EP - 1018

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 14

ER -