Introduction
Materials and methods
Participants
BRCA1 and BRCA2 gene mutation screening test using next-generation sequencing (NGS)
Genetic counselling and medical advice
Genetic counselling
Medical advice
Guidance for patient treatment
Surgical treatment of cancer patients with BRCA1/2 mutations
Chemotherapy and targeted therapy in cancer patients with BRCA1/2 mutations
Statistical analyses
Results
Population characteristics
Characteristics | Number (Mean ± SD) | Percentage (%) |
---|---|---|
Gender | ||
Female | 1,661 | 99.8 |
Male | 3 | 0.2 |
Age (years) | ||
< 35 | 76 (29.88 ± 4.60) | 4.6 |
35–50 | 749 (44.13 ± 4.34) | 45.0 |
> 50 | 839 (58.23 ± 5.96) | 50.4 |
Type of cancer | ||
Breast cancer only | 1,415 | 85.04 |
Ovarian cancer only | 245 | 14.72 |
Both breast and ovarian cancer | 4 | 0.24 |
Mean age of breast cancer (years) | 50.03 ± 9.17 | |
Mean age of ovarian cancer (years) | 53.78 ± 12.15 | |
Mean age of both breast and ovarian cancer (years) | 56.00 ± 8.29 | |
Clinical stage | ||
0-II | 882 | 53.0 |
III-IV | 717 | 43.1 |
Unknown | 65 | 3.9 |
Frequency and distribution of BRCA1 and BRCA2 variants in the Hakka population
Recurrent variants in the BRCA1 and BRCA2 genes in the Hakka population
Gene | Exon/Intron | Mutation | Amino acid change | ClinVar | Number of patients |
---|---|---|---|---|---|
BRCA1 | Exon 5 | c.5212G > A | p.Gly1738Arg | Pathogenic | 1 |
BRCA1 | Exon 5 | c.5209dupA | p.Arg1737Lysfs*93 | Pathogenic | 1 |
BRCA1 | Intron 5 | c.5194-2A > G | - | Likely pathogenic | 1 |
BRCA1 | Exon 7 | c.5096G > A | p.Arg1699Gln | Likely pathogenic | 1 |
BRCA1 | Exon 8 | c.5072C > A | p.Thr1691Lys | Likely pathogenic | 4 |
BRCA1 | Intron 7 | c.4987-5 T > C | - | Pathogenic | 1 |
BRCA1 | Intron 7 | c.4986 + 5G > A | - | Likely pathogenic | 1 |
BRCA1 | Exon 10 | c.4624_4628del | p.Ser1542Alafs*30 | Pathogenic | 1 |
BRCA1 | Exon 11 | c.4484G > A | p.Arg1495Lys | Pathogenic | 1 |
BRCA1 | Exon 11 | c.4467delA | p.Glu1490Asnfs*15 | Pathogenic | 2 |
BRCA1 | Exon 12 | c.4342delA | p.Ser1448Alafs*8 | Pathogenic | 1 |
BRCA1 | Exon 12 | c.4237delG | p.Glu1413Asnfs*2 | Pathogenic | 1 |
BRCA1 | Exon 13 | c.4161_4162del | p.Gln1388Glufs*2 | Pathogenic | 1 |
BRCA1 | Exon 14 | c.4065_4068del | p.Asn1355Lysfs*10 | Pathogenic | 2 |
BRCA1 | Exon 14 | c.4041_4042del | p.Gly1348Asnfs*7 | Pathogenic | 1 |
BRCA1 | Exon 14 | c.3823dupA | p.Ile1275Asnfs*12 | Pathogenic | 1 |
BRCA1 | Exon 14 | c.3817C > T | p.Gln1273* | Pathogenic | 1 |
BRCA1 | Exon 14 | c.3756_3759del | p.Ser1253Argfs*10 | Pathogenic | 5 |
BRCA1 | Exon 14 | c.3607C > T | p.Arg1203Ter | Pathogenic | 1 |
BRCA1 | Exon 14 | c.3333delA | p.Glu1112Asnfs*5 | Pathogenic | 1 |
BRCA1 | Exon 14 | c.2764_2767del | p.Thr922Leufs*77 | Pathogenic | 1 |
BRCA1 | Exon 14 | c.2635G > T | p.Glu879* | Pathogenic | 7 |
BRCA1 | Exon 14 | c.2253_2254del | p.Met751Ilefs*10 | Pathogenic | 1 |
BRCA1 | Exon 14 | c.1961delA | p.Lys654Serfs*47 | Pathogenic | 1 |
BRCA1 | Exon 14 | c.1960_1961del | p.Lys654Valfs*18 | Pathogenic | 1 |
BRCA1 | Exon 14 | c.1881_1884del | p.Ser628Glufs*3 | Pathogenic | 1 |
BRCA1 | Exon 14 | c.1483G > T | p.Glu495* | Pathogenic | 1 |
BRCA1 | Exon 14 | c.1193C > A | p.Ser398* | Pathogenic | 1 |
BRCA1 | Exon 14 | c.981_982del | p.Cys328* | Pathogenic | 2 |
BRCA1 | Exon 14 | c.968delG | p.Gly323Glufs*18 | Pathogenic | 1 |
BRCA1 | Exon 14 | c.938 T > G | p.Leu313* | Pathogenic | 1 |
BRCA1 | Intron 14 | c.671-1G > T | - | Likely pathogenic | 1 |
BRCA1 | Exon 17 | c.520C > T | p.Gln174* | Pathogenic | 1 |
BRCA1 | Exon 17 | c.470_471del | p.Ser157* | Pathogenic | 2 |
BRCA1 | Intron 19 | c.212 + 3A > G | - | Pathogenic | 1 |
BRCA1 | Exon 20 | c.140G > T | p.Cys47Phe | Likely pathogenic | 1 |
BRCA1 | Exon 22 | c.66dupA | p.Glu23Argfs*18 | Pathogenic | 2 |
BRCA1 | Exon 22 | c.1A > G | p.Met1Val | Pathogenic | 1 |
Gene | Exon/Intron | Mutation | Amino acid change | ClinVar | Number of patients |
---|---|---|---|---|---|
BRCA2 | Exon 2 | c.31delT | p.Phe12Leufs*13 | Pathogenic | 1 |
BRCA2 | Exon 8 | c.657_658del | p.Val220Ilefs*4 | Pathogenic | 1 |
BRCA2 | Exon 9 | c.684delT | p.Asn228Lysfs*2 | Pathogenic | 1 |
BRCA2 | Exon 9 | c.750_753del | p.Asp252Valfs*24 | Pathogenic | 1 |
BRCA2 | Exon 10 | c.1281delC | p.Leu428Tyrfs*2 | Pathogenic | 1 |
BRCA2 | Exon 10 | c.1528G > T | p.Glu510* | Pathogenic | 1 |
BRCA2 | Exon 11 | c.2339C > G | p.Ser780* | Pathogenic | 4 |
BRCA2 | Exon 11 | c.2548_2552del | p.Phe851Profs*28 | Pathogenic | 1 |
BRCA2 | Exon 11 | c.2806_2809del | p.Ala938Profs*21 | Pathogenic | 4 |
BRCA2 | Exon 11 | c.3109C > T | p.Gln1037* | Pathogenic | 2 |
BRCA2 | Exon 11 | c.3715_3716del | p.Lys1239Thrfs*3 | Pathogenic | 1 |
BRCA2 | Exon 11 | c.3862_3865del | p.Lys1289Alafs*3 | Pathogenic | 1 |
BRCA2 | Exon 11 | c.4525C > T | p.Gln1509* | Pathogenic | 3 |
BRCA2 | Exon 11 | c.4790delC | p.Ser1597Phefs*20 | Pathogenic | 1 |
BRCA2 | Exon 11 | c.5164_5165del | p.Ser1722Tyrfs*4 | Pathogenic | 7 |
BRCA2 | Exon 11 | c.5242delA | p.Ser1748Alafs*29 | Pathogenic | 1 |
BRCA2 | Exon 11 | c.5467A > T | p.Lys1823* | Pathogenic | 1 |
BRCA2 | Exon 11 | c.5574_5577del | p.Ile1859Lysfs*3 | Pathogenic | 2 |
BRCA2 | Exon 11 | c.5645C > A | p.Ser1882* | Pathogenic | 1 |
BRCA2 | Exon 11 | c.5682C > G | p.Tyr1894* | Pathogenic | 1 |
BRCA2 | Exon 11 | c.5718_5719del | p.Leu1908Argfs*2 | Pathogenic | 1 |
BRCA2 | Exon 11 | c.6096dupT | p.Ile2033Tyrfs*16 | Pathogenic | 2 |
BRCA2 | Exon 11 | c.6581delT | p.Ile2194Metfs*12 | Pathogenic | 1 |
BRCA2 | Exon 15 | c.7558C > T | p.Arg2520* | Pathogenic | 1 |
BRCA2 | Intron 18 | c.8331 + 1G > A | - | Likely pathogenic | 1 |
BRCA2 | Intron 22 | c.8954-5A > G | - | Likely pathogenic | 2 |
BRCA2 | Exon 23 | c.9073_9078T | p.Ile3025Phefs*17 | Pathogenic | 1 |
BRCA2 | Exon 25 | c.9400delG | p.Gly3134Alafs*29 | Pathogenic | 1 |
Genetic distribution of pathogenic BRCA1 and BRCA2 variants
Ethnicity comparison of BRCA1 and BRCA2 pathogenic variants
Population | BRCA1 | BRCA2 | Ref | ||||
---|---|---|---|---|---|---|---|
First | Second | Third | First | Second | Third | ||
Asian | |||||||
Our data (Hakka) | c.2635G > T | c.3756_3759delGTCT | c.4065_4068delTCAA | c.5164_5165delAG | c.2339C > G | c.2806_2809delACAA | |
Chinese | c.5470_5477delATTGGGCA | c.2612C > T | c.3548A > G | c.3109C > T | c.2806_2809delAAAC | c.5164_5165delAG | [25] |
Vietnamese | c.5251C > T | c.4997dup | No hotspot | [19] | |||
Indian | c.68_69delAG | c.5074 + 1G > A | c.3607C > T | c.5722_5723delCT | [10] | ||
Pakistani | c.4508C > A | c.4065_4068delTCAA | c.68_69delAG | c.3109C > T | c.4829_4830delTG | [20] | |
Korean | c.390C > A | c.3627dupA | c.922_924delAGCinsT | c.7480C > T | c.1399A > T | c.5576_5579delTTAA | [21] |
European | |||||||
Ashkenazi Jewish | c.68_69delAG | c.5266dupC | c.5946delT | [11] | |||
Polish | c.5266dupC | c.181 T > G | c.5251C > T | - | [16] | ||
Spanish | c.5123C > A | c.211A > G | - | c.2806_2809delAAAC | c.6024dupG | c.6275_6276delTT | [22] |
Italian | c.5266dupC | c.2406_2409delGAGT | c.5062_5064delGTT | c.6313delA | c.5722_5723delCT | - | [17] |
Latin America and the Caribbean populations | c.5123C > A | - | - | c.6174delT | - | - | [23] |
Ashkenazi Jewish in Argentina | c.68_69delAG | c.5266dupC | - | c.5946delT | - | - | [12] |
Southern Brazilian | c.5266dupC | c.5177_5180delGAAA | c.5251C > T | c.2808_2811delACAA | c.1138delA | - | [18] |
Peruvian | c.68_69delAG | - | - | c.2808_2811delACAA | - | - | [13] |
African | |||||||
South African Indian | c.68_69delAG | c.4308_4309delTT | - | c.8754 + 1G > A | c.4003G > T | - | [14] |
South African | c.68_69delAG | c.1374delC | c.2641G > T | c.7934delG | c.5771_5774del | c.6448_6449dup | [15] |
North African | c.211dupA | c.798_799delTT | c.5266dupC | c.1310_1313delAAGA | - | - | [24] |