Association of Common Genetic Variants With Contralateral Breast Cancer Risk in the WECARE Study

被引：28

作者：

Robson, Mark E. ^{[1
,3
,4
]}

Reiner, Anne S. ^{[2
,3
]}

Brooks, Jennifer D. ^{[5
]}

Concannon, Patrick J. ^{[6
]}

John, Esther M. ^{[7
,9
]}

Mellemkjaer, Lene ^{[10
]}

Bernstein, Leslie ^{[11
]}

Malone, Kathleen E. ^{[12
]}

Knight, Julia A. ^{[5
,13
]}

Lynch, Charles F. ^{[14
]}

Woods, Meghan ^{[2
,3
]}

Liang, Xiaolin ^{[2
,3
]}

Haile, Robert W. ^{[8
,9
]}

Duggan, David J. ^{[15
]}

Shore, Roy E. ^{[16
]}

Smith, Susan A. ^{[17
]}

Thomas, Duncan C. ^{[18
,20
]}

Stram, Daniel O. ^{[19
,20
]}

Bernstein, Jonine L. ^{[2
,3
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[3] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA

[4] Cornell Univ, Dept Med, Weill Cornell Med Coll, New York, NY 10021 USA

[5] Univ Toronto, Dalla Lana Sch Publ Hlth Sci, Epidemiol Div, Toronto, ON, Canada

[6] Univ Florida, Genet Inst, Gainesville, FL USA

[7] Canc Prevent Inst Calif, Dept Hlth Res & Policy, Div Epidemiol, Fremont, CA USA

[8] Stanford Sch Med, Div Oncol, Dept Med, Stanford, CA USA

[9] Stanford Sch Med, Stanford, CA USA

[10] Danish Canc Soc, Copenhagen, Denmark

[11] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA

[12] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA

[13] Sinai Hlth Syst, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada

[14] Univ Iowa, Dept Epidemiol, Iowa City, IA USA

[15] Translat Genom Res Inst TGen, Integrated Canc Genom Div, Phoenix, AZ USA

[16] NYU, Dept Populat Hlth, New York, NY USA

[17] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA

[18] Univ Southern Calif, Div Biostat, Los Angeles, CA USA

[19] Univ Southern Calif, Dept Prevent Med, Div Biostat & Genet Epidemiol, Los Angeles, CA 90089 USA

[20] Univ Southern Calif, Los Angeles, CA USA

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2017年 / 109卷 / 10期

基金：

美国国家卫生研究院;

关键词：

WOMENS ENVIRONMENTAL CANCER; GENOME-WIDE ASSOCIATION; PROPHYLACTIC MASTECTOMY; ATM GENE; RADIATION EPIDEMIOLOGY; MUTATIONS; CARRIERS; LOCI;

D O I：

10.1093/jnci/djx051

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Women with unilateral breast cancer (UBC) are at risk of developing a subsequent contralateral breast cancer (CBC). Common variants are associated with breast cancer risk. Whether these influence CBC risk is unknown. Methods: Participants were breast cancer cases from the population-based Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study. Sixty-seven established breast cancer risk loci were genotyped directly or by imputation in 1459 case subjects with CBC and 2126 UBC control subjects. An unweighted polygenic risk score (PRS) was created by summing the number of risk alleles for each directly genotyped single nucleotide polymorphism (SNP), or for imputed loci, the imputed dosage. A weighted PRS was calculated similarly, but where each SNP's contribution was weighted by the published per-allele log odds ratio. Unweighted and weighted polygenic risk scores and CBC risk were modeled using conditional logistic regression. Cumulative CBC risk was estimated and benchmarked using Surveillance, Epidemiology, and End Results population incidence rates. Results: Both unweighted and weighted PRS were statistically significantly associated with CBC risk. The adjusted risk ratio of CBC in women in the upper quartile of unweighted PRS compared with the lowest quartile was 1.63 (95% confidence interval [CI] - 1.33 to 2.00). The estimated 10-year cumulative risk for women in the upper quartile of the unweighted PRS was 7.4% (95% CI = 6.0% to 9.1%). For women in the upper quartile of the weighted PRS, the risk ratio for CBC was 1.75 (95% CI = 1.41 to 2.18) compared with women in the lowest quartile. There was no statistically significant heterogeneity by age, treatment (radiation therapy dose, tamoxifen, chemotherapy), estrogen receptor status of the first primary, histology of the first primary, length of at-risk period for CBC, or breast cancer family history. Conclusions: Common genomic variants associated with the development of first primary breast cancer are also associated with the development of CBC; the risk is strongest among those who carry more risk alleles.

引用

页数：6

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