Prevalence and spectrum of BRCA germline variants in mainland Chinese familial breast and ovarian cancer patients

Abstract

Germline mutations in BRCA1 and BRCA2 are the most penetrating genetic predispositions for breast and ovarian cancer, and their presence is largely ethnic-specific. Comprehensive information about the prevalence and spectrum of BRCA mutations has been collected in European and North American populations. However, similar information is lacking in other populations, including the mainland Chinese population despite its large size of 1.4 billion accounting for one fifth of the world's population. Herein, we performed an extensive literature analysis to collect BRCA variants identified from mainland Chinese familial breast and ovarian cancer patients. We observed 137 distinct BRCA1 variants in 409 of 3,844 and 80 distinct BRCA2 variants in 157 of 3,024 mainland Chinese patients, with an estimated prevalence of 10.6% for BRCA1 and 5.2% for BRCA2. Of these variants, only 40.3% in BRCA1 and 42.5% in BRCA2 are listed in current Breast Cancer Information Core database. We observed higher frequent variation in BRCA1 exons 11A, 11C, 11D, and 24 and BRCA2 exon 10 in Chinese patients than in the patients of other populations. The most common pathogenic variant in BRCA1 wasc.981_982delAT in exon 11A, and in BRCA2 c.3195_3198delTAAT in exon 11B and c.5576_5579delTTAA in exon 11E; the most common novel variant in BRCA1 was c.919A>G in exon 10A, and in BRCA2 c.7142delC in exon 14. None of the variants overlap with the founder mutations in other populations. Our analysis indicates that the prevalence of BRCA variation in mainland Chinese familial breast and ovarian cancer patients is at a level similar to but the spectrum is substantially different from the ones of other populations.

Keywords: BRCA1; BRCA2; familial breast and ovarian cancer; germline variant; mainland Chinese.

Figure 1. Outline of the study

It shows the steps taken to extract information about BRCA variation in mainland Chinese familial breast and ovarian cancer patients.

Figure 2. Geographic locations of the original studies

The original studies were performed in 15 provinces and cities in mainland China. Of these, 13 were in east coast area of Han Chinese and two were in Xinjiang and Ningxia of other ethnic groups.

Figure 3. Comparison of exon distribution frequencies of BRCA variation between mainland Chinese and BIC populations

Relative ratios between these two datasets were used for the comparison (see text for the details). Chi square (χ²) and Fisher exact test were used for statistics analysis. “*” refers to p < 0.05 (actual P values listed in Supplementary Table 5). A. Variant distribution in BRCA1. B. Variant distribution in BRCA2.

Figure 4. Matching BRCA variants to the BIC database

The 137 BRCA1 and 80 BRCA2 distinct variants from mainland Chinese patients were compared with the 1,781 BRCA1 and 2,000 BRCA2 distinct variants in the BIC database. Of the Chinese variants, 56 BRCA1 and 34 BRCA2 variants were matched, whereas 82 BRCA1 and 46 BRCA2 variants were not.