BRCA1/2 gene mutations in Uyghur and Han women with sporadic breast cancer in the xinjiang region of China

Objective: This study investigated the prevalence of BRCA1/2 gene mutations and their relationship with clinical pathological parameters in Uyghur and Han sporadic breast cancer patients in the Xinjiang Uyghur Autonomous Region. Methods: Polymerase chain reaction (PCR) and DNA sequencing were used to detect mutations of the BRCA1 (exons 2, 11 (11A and 11B) and 20) and BRCA2 (exon 11) genes in paraffin-embedded tissues obtained from 170 sporadic breast cancer patients (85 Uyghur and 85 Han) in the Xinjiang Uyghur Autonomous Region. Results: The prevalence of BRCA mutations in sporadic breast cancer cases was 9.41% (16/170). Of these, 8.24% (14/170) harbored BRCA1 mutations and 1.18% (2/170) BRCA2 mutations. Among the 14 patients with BRCA1 mutations, the detection rates of mutations in exons 2, 11 and 20 were 21.43% (3/14), 64.29% (9/14) and 14.29% (2/14), respectively. One of the sixteen mutations was at the -5382 locus in BRCA1 (a hot-spot mutation site in Ashkenazi Jews); seven cases exhibited novel mutations. There were two germline mutations in exon 11 of the BRCA2 gene. The rates of BRCA gene mutations in Uyghur and Han patients were 10.59% (9/85) and 8.24% (7/85), respectively; this difference was not significant (P > 0.05). Patients with BRCA gene mutations were on average 41.31±6.34 years old, and those without mutations were 49.67±12.63 years old. Thus, the mutation group was younger than the no-mutation group, and the age of onset of breast cancer in the total population was ≤ 50 years. Patients with amenorrhea comprised 18.75% (3/16) of the mutation group, and 81.25% (13/16) of patients were premenopausal; this difference was significant (P < 0.05). Analysis of the relationship between BRCA gene mutation status and clinical pathological features showed no significant difference (P > 0.05) in clinical staging, lymph node metastasis, tumor diameter, fertility status and age at menarche. BRCA mutations showed no significant differences among the patients of different molecular classifications (P > 0.05). Conclusion: The prevalence of BRCA1 mutations was significantly higher than that of BRCA2 mutations in sporadic breast cancer patients in Xinjiang. This study detected one mutation of the BRCA1 gene at the -5382 locus (a hot spot in Jewish individuals) and seven novel mutations, perhaps is the founder mutation of the local area in patients with breast cancer mutations. The BRCA mutations detected did not differ markedly between Uyghur and Han patients. Pre-menopausal patients with breast cancer < 50 years old in Xinjiang may be at high risk of BRCA1/2 mutations, and screening of the BRCA gene should be performed in such individuals.