Additive Interactions Between Susceptibility Single-Nucleotide Polymorphisms Identified in Genome-Wide Association Studies and Breast Cancer Risk Factors in the Breast and Prostate Cancer Cohort Consortium

被引：37

作者：

Joshi, Amit D. ^{[1
,3
]}

Lindstrom, Sara ^{[1
]}

Husing, Anika ^{[2
]}

Barrdahl, Myrto ^{[2
]}

VanderWeele, Tyler J. ^{[3
,5
]}

Campa, Daniele ^{[4
,6
]}

Canzian, Federico ^{[6
]}

Gaudet, Mia M. ^{[7
]}

Figueroa, Jonine D. ^{[8
]}

Baglietto, Laura ^{[9
,10
]}

Berg, Christine D. ^{[11
]}

Buring, Julie E. ^{[12
,13
]}

Chanock, Stephen J. ^{[8
]}

Chirlaque, Maria-Dolores ^{[14
,15
]}

Diver, W. Ryan ^{[16
]}

Dossus, Laure ^{[17
,18
]}

Giles, Graham G. ^{[9
,10
,19
]}

Haiman, Christopher A. ^{[20
]}

Hankinson, Susan E. ^{[21
]}

Henderson, Brian E. ^{[20
]}

Hoover, Robert N. ^{[8
]}

Hunter, David J. ^{[1
]}

Isaacs, Claudine ^{[22
]}

Kaaks, Rudolf ^{[2
]}

Kolonel, Laurence N. ^{[23
]}

Krogh, Vittorio ^{[24
]}

Le Marchand, Loic ^{[25
]}

Lee, I-Min ^{[12
,13
]}

Lund, Eiliv ^{[26
]}

McCarty, Catherine A. ^{[27
]}

Overvad, Kim ^{[28
]}

Peeters, Petra H. ^{[29
,30
]}

Riboli, Elio ^{[30
]}

Schumacher, Fredrick ^{[20
]}

Severi, Gianluca ^{[9
,10
]}

Stram, Daniel O. ^{[20
]}

Sund, Malin ^{[31
]}

Thun, Michael J. ^{[16
]}

Travis, Ruth C. ^{[32
]}

Trichopoulos, Dimitrios ^{[3
,33
,34
]}

Willett, Walter C. ^{[35
]}

Zhang, Shumin ^{[12
,13
]}

Ziegler, Regina G. ^{[8
]}

Kraft, Peter ^{[1
,3
]}

机构：

[1] Harvard Univ, Program Genet Epidemiol & Stat Genet, Sch Publ Hlth, Boston, MA 02115 USA

[2] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[3] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA

[4] Univ Pisa, Dept Biol, Pisa, Italy

[5] Harvard Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02115 USA

[6] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany

[7] Amer Canc Soc, Genet Epidemiol Unit, Atlanta, GA 30329 USA

[8] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[9] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia

[10] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Sch Populat Hlth, Melbourne, Vic, Australia

[11] NCI, Div Canc Prevent, Bethesda, MD 20892 USA

[12] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA

[13] Harvard Univ, Sch Med, Boston, MA 02115 USA

[14] Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain

[15] Consorcio Invest Biomed Epidemiol & Salud Publ, Madrid, Spain

[16] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

[17] Inst Gustave Roussy, INSERM, Ctr Res Epidemiol & Populat Hlth, U1018, F-94805 Villejuif, France

[18] Paris South Univ, Unite Mixte Rech Sante 1018, Villejuif, France

[19] Monash Univ, Fac Med, Melbourne, Vic 3004, Australia

[20] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[21] Univ Massachusetts, Div Biostat & Epidemiol, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA

[22] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA

[23] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA

[24] Fdn IRCCS Ist Nazl Tumori, Epidemiol & Prevent Unit, Milan, Italy

[25] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA

[26] Univ Tromso, Inst Community Med, Tromso, Norway

[27] Essentia Inst Rural Hlth, Duluth, MN USA

[28] Aarhus Univ, Epidemiol Sect, Dept Publ Hlth, Aarhus, Denmark

[29] Univ Med Ctr Utrecht, Dept Epidemiol, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[30] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Fac Med, Dept Epidemiol & Biostat, London, England

[31] Umea Univ Hosp, Dept Surg, S-90185 Umea, Sweden

[32] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England

[33] Hellen Hlth Fdn, Athens, Greece

[34] Acad Athens, Bur Epidemiol Res, Athens, Greece

[35] Harvard Univ, Dept Nutr, Sch Publ Hlth, Boston, MA 02115 USA

来源：

AMERICAN JOURNAL OF EPIDEMIOLOGY | 2014年 / 180卷 / 10期

基金：

美国国家卫生研究院;

关键词：

additive interactions; breast cancer; genome-wide association studies; single-nucleotide polymorphisms; COMMON VARIANTS; CONFER SUSCEPTIBILITY; CONFIDENCE-INTERVALS; LIFE-STYLE; PREDICTION; ALLELES; LOCI; PREVENTION; RAD51L1; MODELS;

D O I：

10.1093/aje/kwu214

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

1004 ; 120402 ;

摘要：

Additive interactions can have public health and etiological implications but are infrequently reported. We assessed departures from additivity on the absolute risk scale between 9 established breast cancer risk factors and 23 susceptibility single-nucleotide polymorphisms (SNPs) identified from genome-wide association studies among 10,146 non-Hispanic white breast cancer cases and 12,760 controls within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. We estimated the relative excess risk due to interaction and its 95% confidence interval for each pairwise combination of SNPs and nongenetic risk factors using age- and cohort-adjusted logistic regression models. After correction for multiple comparisons, we identified a statistically significant relative excess risk due to interaction (uncorrected P = 4.51 x 10(-5)) between a SNP in the DNA repair protein RAD51 homolog 2 gene (RAD51L1; rs10483813) and body mass index (weight (kg)/height (m)(2)). We also compared additive and multiplicative polygenic risk prediction models using per-allele odds ratio estimates from previous studies for breast-cancer susceptibility SNPs and observed that the multiplicative model had a substantially better goodness of fit than the additive model.

引用

页码：1018 / 1027

页数：10

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