Dataset Information

Germline breast cancer susceptibility genes, tumor characteristics, and survival.

ABSTRACT:

Background

Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent.

Methods

Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease.

Results

PTV_9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35-5.17], moderately vs well-differentiated 2.33 [1.56-3.49]), as well as luminal B [HER-] and triple-negative subtypes (vs luminal A 2.15 [1.58-2.92] and 2.85 [2.17-3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2-] subtype remained significant after excluding BRCA1/2 carriers. PTV_25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV_25genes carriership, but not PTV_9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16-2.28]).

Conclusions

PTV_9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions.

SUBMITTER: Ho PJ

PROVIDER: S-EPMC8638193 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Germline breast cancer susceptibility genes, tumor characteristics, and survival.

Ho Peh Joo PJ Khng Alexis J AJ Loh Hui Wen HW Ho Weang-Kee WK Yip Cheng Har CH Mohd-Taib Nur Aishah NA Tan Veronique Kiak Mien VKM Tan Benita Kiat-Tee BK Tan Su-Ming SM Tan Ern Yu EY Lim Swee Ho SH Jamaris Suniza S Sim Yirong Y Wong Fuh Yong FY Ngeow Joanne J Lim Elaine Hsuen EH Tai Mei Chee MC Wijaya Eldarina Azfar EA Lee Soo Chin SC Chan Ching Wan CW Buhari Shaik Ahmad SA Chan Patrick M Y PMY Chen Juliana J C JJC Seah Jaime Chin Mui JCM Lee Wai Peng WP Mok Chi Wei CW Lim Geok Hoon GH Woo Evan E Kim Sung-Won SW Lee Jong Won JW Lee Min Hyuk MH Park Sue K SK Dunning Alison M AM Easton Douglas F DF Schmidt Marjanka K MK Teo Soo-Hwang SH Li Jingmei J Hartman Mikael M

Genome medicine 20211202 1

<h4>Background</h4>Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent.<h4>Methods</h4>Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD ...[more]

PMID: 34857041

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Dataset Information

Germline breast cancer susceptibility genes, tumor characteristics, and survival.

Background

Methods

Results

Conclusions

Publications

Germline breast cancer susceptibility genes, tumor characteristics, and survival.

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