Prevalence ofBRCA1andBRCA2Germline Mutations in Breast Cancer Women of Multiple Ethnic Region in Northwest China

Abstract

PurposeThe aim of this study is to further understand the status of BRCA1 and BRCA2 mutation among Chinese high-risk breast cancer patients in multiple-ethnic regions of China.MethodsA total of 79 blood samples of high-risk breast cancer patients from Xinjiang Uyghur autonomous region were analyzed by PCR-DHPLC sequencing analysis.ResultsAnalysis with full length of the two genes identified a total of 6 deleterious mutations (2073delA, 2394C-T [Q759X] and IVS16+1G>A in BRCA1; 1627A-T [K467X], 6873delCTCC and 9481delA in BRCA2) in this cohort. The prevalence of BRCA1/2 germline mutation was about 7.6% (6/79) in the Xinjiang multiple ethnic region of China. Among them, 3 novel deleterious mutations, 2073delA in BRCA1 (Han ethnic Chinese) and BRCA2 variants 6873delCTCC and 9481delA (both are Kazakh ethnic Chinese), were identified and they had never been reported in breast cancer information core (BIC) database before. 2394C-T (Q759X) and IVS16+1G>A, in BRCA1 and BRCA2 variants 1627A-T were previously reported in other populations but not Chinese. Among 6 of the BRCA-related tumors, three BRCA1- and one BRCA2-associated tumors were in triple negative (estrogen receptor, progesterone receptor, and HER2 negative expressed) status and exhibited a high tumor grade. So far none of these 6 deleterious mutations were reported in ethnic Han Chinese.ConclusionBRCA germline mutation in Chinese multiple ethnicity region may exhibit different genotypes compared to ethnic Han Chinese in other regions. These differences may arise from interaction of genetic background and environmental factors.

Mutational analysis of BRCA1/2 gene and pathologic characteristics from Kazakh population with sporadic breast cancer in northwestern China

“…Thus, previous studies have examined the function of these 2 sites (Karimian Fathi et al, 2014;Samel et al, 2014). Currently, only 2 deleterious mutations have been found in the Kazakh population in China (Ou et al, 2013). BRCA1/BRCA2 deleterious mutations were not detected in our study, which may be because the subjects were not high-risk patients, such as some patients are with family history or of the triple-negative type.…”

“…The breast cancer characteristics of Kazakhs include low incidence, early onset age, later clinical stage, and poor prognosis. To date, few studies examining the spectrum of BRCA mutations in China's Kazakh populations have been conducted, and most were performed in Han and Uygur populations (Zhang et al, 2012;Ou et al, 2013;Cao et al, 2014).…”

Differences in Incidence, Mortality and Survival of Breast Cancer by Regions and Countries in Asia and Contributing Factors

“…The mutation rate of BRCA1 and BRCA2 genes among high risk breast cancer patients who were suspected to have hereditary breast/ovarian cancer also varies by country, ranging from 3.8% in Hong Kong (BRCA1) (Tang et al, 1999), 5.1% in Iran (BRCA1) (Kooshyar et al, 2013), 7.6% in northwest China (BRCA1/2) (Ou et al, 2013), 7.8% in Indonesia (BRCA1/2) (Purnomosari et al, 2007), 8.6%-12.7 % in Korea (BRCA1/2) (Ahn et al, 2004;Son et al, 2012), and 26.7% in Japan (BRCA1/2) (Sugano et al, 2008). The BRCA1 and BRCA2 mutation rates among all breast cancer cases were 1.1% in Shanghai (Suter et al, 2004) and 2.8% in Korea (Ahn et al, 2004).…”

Frecuencia de las mutaciones en los genes BRCA en mujeres con agregación familiar de cáncer de glándula mamaria/ovario

“…Adicionalmente, entre un 30% y 40% de los tumores malignos esporádicos están asociados con la pérdida de expresión del gen BRCA1 (Han et al, 2013;O'Donovan & Livingston, 2010;Ou et al, 2013). El riesgo de desarrollar CGM en individuos portadores de alguna mutación en BRCA es del 45% al 80%; para el cáncer de ovario es del 45% al 60% (Mahfoudh et al, 2012;Narod & Rodríguez, 2011;O'Donovan & Livingston, 2010;Paul & Paul, 2014).…”