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Assessment of an APOBEC3B truncating mutation, c.783delG, in patients with breast cancer.

Abstract：

PURPOSE:APOBEC3B belongs to the family of DNA-editing enzymes. A copy number variant targeting the genomic APOBEC3A-APOBEC3B locus has a significant impact on breast cancer risk, but the relative contribution of APOBEC3B is uncertain. In this study, we investigate a loss-of-function mutation that selectively targets APOBEC3B, for its association with breast cancer risk. METHODS:We performed exome sequencing on genomic DNA samples of 6 Byelorussian patients with familial breast cancer. We then studied through mutation-specific genotyping four hospital-based breast cancer case-control series from Belarus, Russia, Germany, and Iran, respectively, comprising a total of 3070 breast cancer patients and 2878 healthy females. Results were evaluated using fixed-effects meta-analyses. RESULTS:Exome sequencing uncovered a frameshift mutation, APOBEC3B*c.783delG, that was recurrent in the study populations. Subsequent genotyping identified this mutation in 23 additional breast cancer cases and 9 healthy female controls, with an adjusted Odds Ratio 2.29 (95% CI 1.04; 5.03, P = 0.04) in the combined analysis. There was an enrichment of the c.783delG mutation in patients with breast cancer diagnosed below 50 years of age (OR 3.22, 95% CI 1.37; 7.56, P = 0.007). CONCLUSIONS:APOBEC3B*c.783delG showed evidence of modest association with breast cancer and seemed to contribute to earlier onset of the disease. These results may need to be reconciled with proposals to consider APOBEC3B as a possible therapeutic target in breast cancer.

journal_name

Breast Cancer Res Treat

journal_title

Breast cancer research and treatment

authors

Radmanesh H,Spethmann T,Enßen J,Schürmann P,Bhuju S,Geffers R,Antonenkova N,Khusnutdinova E,Sadr-Nabavi A,Shandiz FH,Park-Simon TW,Hillemanns P,Christiansen H,Bogdanova N,Dörk T

doi

10.1007/s10549-016-4100-9

subject

Has Abstract

pub_date

2017-02-01 00:00:00

pages

31-37

issue

1

eissn

0167-6806

issn

1573-7217

pii

10.1007/s10549-016-4100-9

journal_volume

162

pub_type

杂志文章,多中心研究

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