Targeted Resequencing of the Coding Sequence of 38 Genes Near Breast Cancer GWAS Loci in a Large Case-Control Study

被引：7

作者：

Decker, Brennan ^{[1
,2
,4
]}

Allen, Jamie ^{[1
]}

Luccarini, Craig ^{[3
]}

Pooley, Karen A. ^{[1
]}

Shah, Mitul ^{[3
]}

Bolla, Manjeet K. ^{[1
]}

Wang, Qin ^{[1
]}

Ahmed, Shahana ^{[3
]}

Baynes, Caroline ^{[1
]}

Conroy, Don M. ^{[1
]}

Brown, Judith ^{[1
]}

Luben, Robert ^{[1
]}

Ostrander, Elaine A. ^{[2
]}

Pharoah, Paul D. P. ^{[1
,3
]}

Dunning, Alison M. ^{[3
]}

Easton, Douglas F. ^{[1
,3
]}

机构：

[1] Univ Cambridge, Dept Publ & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England

[2] NHGRI, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA

[3] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England

[4] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

来源：

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION | 2019年 / 28卷 / 04期

关键词：

D O I：

10.1158/1055-9965.EPI-18-0298

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Genes regulated by breast cancer risk alleles identified through genome-wide association studies (GWAS) may harbor rare coding risk alleles. Methods: We sequenced the coding regions for 38 genes within 500 kb of 38 lead GWAS SNPs in 13,538 breast cancer cases and 5,518 controls. Results: Truncating variants in these genes were rare, and were not associated with breast cancer risk. Burden testing of rare missense variants highlighted 5 genes with some suggestion of an association with breast cancer, although none met the multiple testing thresholds: MKL1, FTO, NEK10, MDM4, and COX11. Six common alleles in COX11, MAP3K1 (two), and NEK10 (three) were associated at the P < 0.0001 significance level, but these likely reflect linkage disequilibrium with causal regulatory variants. Conclusions: There was no evidence that rare coding variants in these genes confer substantial breast cancer risks. However, more modest effect sizes could not be ruled out. Impact: We tested the hypothesis that rare variants in 38 genes near breast cancer GWAS loci may mediate risk. These variants do not appear to play a major role in breast cancer heritability.

引用

页码：822 / 825

页数：4

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