Predictive Factors for BRCA1 and BRCA2 Genetic Testing in an Asian Clinic-Based Population

Wong, Edward Sern Yuen; Shekar, Sandhya; Chan, Claire Hian Tzer; Hong, Lewis Z.; Poon, Suk-Yean; Silla, Toomas; Lin, Clarabelle Bitong; Kumar, Vikrant; Dávila, Sonia; Voorhoeve, Mathijs; Thike, Aye Aye; Yap, Yoon Sim; Tan, Puay Hoon; Tan, Min‐Han; Ang, Peter; Lee, Ann S. G.

doi:10.1371/journal.pone.0134408

Cited by 15 publications

(12 citation statements)

References 32 publications

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“…High costs have long been cited as a barrier to entry for genetic testing internationally26 as well as locally 3 6. However, data gathered from our study showed that the relationship between cost and uptake rate is more complex than previously understood.…”

Section: Discussionmentioning

confidence: 68%

Impact of subsidies on cancer genetic testing uptake in Singapore

Yuen

Zhou

et al. 2016

J Med Genet

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Section: Discussionmentioning

confidence: 68%

Impact of subsidies on cancer genetic testing uptake in Singapore

Yuen

Zhou

et al. 2016

J Med Genet

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“…A total of 28 novel potentially pathogenic variants were detected in BRCA1 , BRCA2 , PALB2 , TP53 , PTEN , NF1 , CDH1 , MSH6 and PMS2 ( Table 2 ) by our group in this study and previous studies. 4–6 …”

Section: Resultsmentioning

confidence: 99%

Inherited breast cancer predisposition in Asians: multigene panel testing outcomes from Singapore

et al. 2016

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Genetic testing for germline mutations in breast cancer predisposition genes can potentially identify individuals at a high risk of developing breast and/or ovarian cancer. There is a paucity of such mutational information for Asians. Panel testing of 25 cancer susceptibility genes and BRCA1/2 deletion/duplication analysis was performed for 220 Asian breast cancer patients or their family members referred for genetics risk assessment. All 220 participants had at least one high-risk feature: having a family history of breast and/or ovarian cancer in first- and/or second-degree relatives; having breast and ovarian cancer in the same individual or bilateral breast cancer; having early-onset breast cancer or ovarian cancer (⩽40 years of age). We identified 67 pathogenic variants in 66 (30.0%) patients. Of these, 19 (28.3%) occurred in BRCA1, 16 (23.9%) in BRCA2, 7 (10.4%) in PALB2, 6 (9.0%) in TP53, 2 (3.0%) in PTEN, 2 (3.0%) in CDH1 and 15 (22.4%) in other predisposition genes. Notably, 47.8% of pathogenic variants were in non-BRCA1/2 genes. Of the 66 patients with pathogenic mutations, 63.6% (42/66) were under the age of 40 years. Family history of breast and/or ovarian cancer is enriched in patients with BRCA1/2 pathogenic variants but less predictive for non-BRCA1/2 related pathogenic variations. We detected a median of three variants of unknown significance (VUS) per gene (range 0–21). Custom gene panel testing is feasible and useful for the detection of pathogenic mutations and should be done in the setting of a formal clinical cancer genetics service given the rate of VUS.

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“…In the same study, the most common pathogenic BRCA2 variants were found to be c.3195_3198delTAAT (p.Asn1066Leufs*10) (n = 5) and c.5576_5579delTTAA (p.Ile1859Lysfs*3) (n = 5) in exon 11 [ 39 ]. The BRCA2 mutation c.7480C>T is enriched in Korean familial BC patients [ 49 ], and Wong et al reported four recurrent mutations in BRCA1 (p.Y1127* (c.3381T4A), E23Rfs*18 (c.67_68delinsAG), p.E1112Nfs*5 (c.3333delA), p.T1691K (c.5072C4)) and one BRCA2 mutation (p.C161W (c.483T4G)) in a population from Singapore [ 50 ]. In our hospital cohort, we detected one recurrent BRCA1 mutation (p.R1203X (c.3607C>T)) in one double cancer patient and in one OC patient without a family history ( Table 2 ), and the BRCA2 p.S1722fs (c.5164_5165 delAG) mutation was detected in two OC patients [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

The frequency of cancer predisposition gene mutations in hereditary breast and ovarian cancer patients in Taiwan: From BRCA1/2 to multi-gene panels

et al. 2017

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An important role of genetic factors in the development of breast cancer (BC) or ovarian cancer (OC) in Taiwanese (ethnic Chinese) patients has been suggested. However, other than germline BRCA1 or BRCA2 mutations, which are related to hereditary breast-ovarian cancer (HBOC), cancer-predisposition genes have not been well studied in this population. The aim of the present study was to more accurately summarize the prevalence of genetic mutations in HBOC patients using various gene panels ranging in size from BRCA1/2 alone to multi-gene panels. Among 272 HBOC patients analyzed, the prevalence of BRCA1, BRCA2 and non-BRCA1/2 pathogenic mutations was 7.7% (21/272), 6.8% (16/236) and 8.2% (13/159), respectively. The total mutation rate was 18.4% (50/272). Although no founder mutations were identified in this study, two recurrent mutations, BRCA1 (c.3607C>T) and BRCA2 (c.5164_5165 delAG), were found. The main pathogenic/likely pathogenic mutations in non-BRCA1/2 genes included ATM, BRIP1, FANCI, MSH2, MUYTH, RAD50, RAD51C and TP53. The prevalence rate of gene mutations in HBOC patients did not differ with respect to whether BC or OC was the first diagnosis or they presented a family history of the disease or their age at diagnosis. HBOC patients with both BC and OC exhibited a higher prevalence rate of mutations (50.0%) than patients with OC (25.0%) or BC (8.6%) alone. In conclusion, evaluation of hereditary cancer risk in Taiwan HBOC patients, particularly individuals with double cancer, is strongly encouraged. Panel testing can yield additional genomic information, and widespread and well-designed panel testing will help in assessing more accurate mutational prevalence of risk genes.

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Predictive Factors for BRCA1 and BRCA2 Genetic Testing in an Asian Clinic-Based Population

Cited by 15 publications

References 32 publications

Impact of subsidies on cancer genetic testing uptake in Singapore

Impact of subsidies on cancer genetic testing uptake in Singapore

Inherited breast cancer predisposition in Asians: multigene panel testing outcomes from Singapore

The frequency of cancer predisposition gene mutations in hereditary breast and ovarian cancer patients in Taiwan: From BRCA1/2 to multi-gene panels

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