BRCA1, BRCA2 mutations and the association with the clinicopathological characteristics of women with early-onset breast cancer

Introduction: BRCA1 and BRCA2 mutations have been associated with early-onset breast cancers and adverse clinico-pathological features. To date, there is paucity of studies in Malaysia investigating the relationship between types of BRCA1/2 mutations and clinicopathological characteristics of bre...

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Main Author:	Ghazali, Mohamad Bazli
Format:	Thesis
Language:	English
Published:	2014
Subjects:	RC254-282 Neoplasms Tumors Oncology (including Cancer)
Online Access:	http://eprints.usm.my/39515/1/Dr._Mohamad_Bazli_Ghazali_%28Surgery%29-24_pages.pdf
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spelling	my-usm-ep.395152019-04-12T05:26:04Z BRCA1, BRCA2 mutations and the association with the clinicopathological characteristics of women with early-onset breast cancer 2014 Ghazali, Mohamad Bazli RC254-282 Neoplasms. Tumors. Oncology (including Cancer) Introduction: BRCA1 and BRCA2 mutations have been associated with early-onset breast cancers and adverse clinico-pathological features. To date, there is paucity of studies in Malaysia investigating the relationship between types of BRCA1/2 mutations and clinicopathological characteristics of breast cancers. This study therefore aims to ascertain whether there are differences between different types of BRCA1/2 mutations in terms of clinico-pathological attributes of breast cancers amongst females with early-onset breast cancers in Malaysia. Methodology: Seventy females aged 40 or less with confirmed breast cancer diagnosis that underwent follow-ups at Seberang Jaya Hospital, Penang were recruited into this study. Clinical (age, ethnicity, stage, neo adjuvant therapy, family history of ovarian and breast cancers) and pathological (ER, PR, Her2 status, triple negativity, tumour grades and stages) characteristics of the breast cancers were obtained by retrospectively reviewing the medical records. Three mls of blood was taken from each subject and subjected to DNA extraction. These were then screened for germline mutations of BRCA1 gene (exons 11, 13 and 16) for BRCA2 gene (exons 10 and 11) using allele-specific PCR. Results: The prevalence of BRCA2-only and combined BRCA1 and BRCA1 mutations were 28.6% (95% CI: 18%, 39.2%) and 71.4% (95% CI: 60.8%, 82.0 %), respectively. No wild-type BRCA1 or BRCA2 and BRCA1-only mutations were observed in this study cohort. No significant associations were found between types of BRCA mutations (BRCA2-only mutations vs combined BRCA1 and BRCA2 mutations) and clinico-pathological characteristics of breast tumour. However, three BRCA1 mutations (3232A>G (rs16941, exon 11), 3667A>G (rs16942, exon 11) and 4427T<C (rs1060915, exon 13) were significantly associated with a more advanced tumour size group (p values = 0.032, 0.049 and 0.043, respectively). Besides, 3232A>G (rs16941, exon 11) mutation was also significantly associated with higher risk of HER2-negative (OR 7.50 (95% CI: 1.439, 39.089), p value = 0.017) and triple negative breast carcinoma (OR 4.375 (95% CI: 1.193, 16.038), p value =0.042). No significant associations were found between BRCA2 genotypes and clinico-pathological features of breast carcinoma. Conclusion: Combined BRCA1 and BRCA2 mutations are the most prevalent types of BRCA mutations amongst females with early onset breast cancers, followed by BRCA2-only mutations. Three BRCA1 germline mutations were found to be significantly predictive of a more advanced tumour size group whilst only one BRCA1 mutation was significantly associated with HER2-negative and triple negative breast tumours. Nevertheless, further studies are warranted to address the unresolved issues encountered by this study. 2014 Thesis http://eprints.usm.my/39515/ http://eprints.usm.my/39515/1/Dr._Mohamad_Bazli_Ghazali_%28Surgery%29-24_pages.pdf application/pdf en public masters Universiti Sains Malaysia Pusat Pengajian Sains Perubatan
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	RC254-282 Neoplasms Tumors Oncology (including Cancer)
spellingShingle	RC254-282 Neoplasms Tumors Oncology (including Cancer) Ghazali, Mohamad Bazli BRCA1, BRCA2 mutations and the association with the clinicopathological characteristics of women with early-onset breast cancer
description	Introduction: BRCA1 and BRCA2 mutations have been associated with early-onset breast cancers and adverse clinico-pathological features. To date, there is paucity of studies in Malaysia investigating the relationship between types of BRCA1/2 mutations and clinicopathological characteristics of breast cancers. This study therefore aims to ascertain whether there are differences between different types of BRCA1/2 mutations in terms of clinico-pathological attributes of breast cancers amongst females with early-onset breast cancers in Malaysia. Methodology: Seventy females aged 40 or less with confirmed breast cancer diagnosis that underwent follow-ups at Seberang Jaya Hospital, Penang were recruited into this study. Clinical (age, ethnicity, stage, neo adjuvant therapy, family history of ovarian and breast cancers) and pathological (ER, PR, Her2 status, triple negativity, tumour grades and stages) characteristics of the breast cancers were obtained by retrospectively reviewing the medical records. Three mls of blood was taken from each subject and subjected to DNA extraction. These were then screened for germline mutations of BRCA1 gene (exons 11, 13 and 16) for BRCA2 gene (exons 10 and 11) using allele-specific PCR. Results: The prevalence of BRCA2-only and combined BRCA1 and BRCA1 mutations were 28.6% (95% CI: 18%, 39.2%) and 71.4% (95% CI: 60.8%, 82.0 %), respectively. No wild-type BRCA1 or BRCA2 and BRCA1-only mutations were observed in this study cohort. No significant associations were found between types of BRCA mutations (BRCA2-only mutations vs combined BRCA1 and BRCA2 mutations) and clinico-pathological characteristics of breast tumour. However, three BRCA1 mutations (3232A>G (rs16941, exon 11), 3667A>G (rs16942, exon 11) and 4427T<C (rs1060915, exon 13) were significantly associated with a more advanced tumour size group (p values = 0.032, 0.049 and 0.043, respectively). Besides, 3232A>G (rs16941, exon 11) mutation was also significantly associated with higher risk of HER2-negative (OR 7.50 (95% CI: 1.439, 39.089), p value = 0.017) and triple negative breast carcinoma (OR 4.375 (95% CI: 1.193, 16.038), p value =0.042). No significant associations were found between BRCA2 genotypes and clinico-pathological features of breast carcinoma. Conclusion: Combined BRCA1 and BRCA2 mutations are the most prevalent types of BRCA mutations amongst females with early onset breast cancers, followed by BRCA2-only mutations. Three BRCA1 germline mutations were found to be significantly predictive of a more advanced tumour size group whilst only one BRCA1 mutation was significantly associated with HER2-negative and triple negative breast tumours. Nevertheless, further studies are warranted to address the unresolved issues encountered by this study.
format	Thesis
qualification_level	Master's degree
author	Ghazali, Mohamad Bazli
author_facet	Ghazali, Mohamad Bazli
author_sort	Ghazali, Mohamad Bazli
title	BRCA1, BRCA2 mutations and the association with the clinicopathological characteristics of women with early-onset breast cancer
title_short	BRCA1, BRCA2 mutations and the association with the clinicopathological characteristics of women with early-onset breast cancer
title_full	BRCA1, BRCA2 mutations and the association with the clinicopathological characteristics of women with early-onset breast cancer
title_fullStr	BRCA1, BRCA2 mutations and the association with the clinicopathological characteristics of women with early-onset breast cancer
title_full_unstemmed	BRCA1, BRCA2 mutations and the association with the clinicopathological characteristics of women with early-onset breast cancer
title_sort	brca1, brca2 mutations and the association with the clinicopathological characteristics of women with early-onset breast cancer
granting_institution	Universiti Sains Malaysia
granting_department	Pusat Pengajian Sains Perubatan
publishDate	2014
url	http://eprints.usm.my/39515/1/Dr._Mohamad_Bazli_Ghazali_%28Surgery%29-24_pages.pdf
_version_	1747820757171306496

BRCA1, BRCA2 mutations and the association with the clinicopathological characteristics of women with early-onset breast cancer

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