Dataset Information

Prevalence of PALB2 mutations in breast cancer patients in multi-ethnic Asian population in Malaysia and Singapore.

ABSTRACT:

Background

The partner and localizer of breast cancer 2 (PALB2) is responsible for facilitating BRCA2-mediated DNA repair by serving as a bridging molecule, acting as the physical and functional link between the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risks of developing breast cancer in various populations.

Methods

We evaluated the contribution of PALB2 germline mutations in 122 Asian women with breast cancer, all of whom had significant family history of breast and other cancers. Further screening for nine PALB2 mutations was conducted in 874 Malaysian and 532 Singaporean breast cancer patients, and in 1342 unaffected Malaysian and 541 unaffected Singaporean women.

Results

By analyzing the entire coding region of PALB2, we found two novel truncating mutations and ten missense mutations in families tested negative for BRCA1/2-mutations. One additional novel truncating PALB2 mutation was identified in one patient through genotyping analysis. Our results indicate a low prevalence of deleterious PALB2 mutations and a specific mutation profile within the Malaysian and Singaporean populations.

SUBMITTER: Phuah SY

PROVIDER: S-EPMC3748013 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prevalence of PALB2 mutations in breast cancer patients in multi-ethnic Asian population in Malaysia and Singapore.

Phuah Sze Yee SY Lee Sheau Yee SY Kang Peter P Kang In Nee IN Yoon Sook-Yee SY Thong Meow Keong MK Hartman Mikael M Sng Jen-Hwei JH Yip Cheng Har CH Taib Nur Aishah Mohd NA Teo Soo-Hwang SH

PloS one 20130820 8

<h4>Background</h4>The partner and localizer of breast cancer 2 (PALB2) is responsible for facilitating BRCA2-mediated DNA repair by serving as a bridging molecule, acting as the physical and functional link between the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risks of developing breast cancer in various populations.<h4>Methods</h4>We evaluated the contribution of PALB2 germline m ...[more]

PMID: 23977390

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Project description:BackgroundCancer has become the leading cause of mortality in Singapore and among other Asian populations worldwide. Despite the presence of National Cancer Screening programmes in Singapore, less than half of the population has had timely screening according to guidelines. The underlying factors of poor cancer screening rates and health outcomes among Asian ethnic groups remain poorly understood. We therefore examined cancer screening participation rates and screening behavior in a multi-ethnic Singapore population.MethodsWe collected data from 7,125 respondents of the 2015-2016 Singapore Community Health Study. Factors associated with cervical, breast, and colorectal cancer screening were evaluated using modified Poisson regression. Adjusted prevalence ratios were computed with 95% confidence intervals after adjusting for confounders.ResultsThe mean age of the respondents was 57.7 ± 10.9 years; 58.9% were female and were predominately Chinese (73.0%), followed by Malay (14.2%), and Indian (10.9%). Less than half of the respondents in the recommended age groups had undergone cancer screening (cervical, 43%; breast, 35.1%; colorectal, 27.3%). Malay respondents were significantly less likely to screen as recommended for cervical (aPR = 0.75, CI = 0.65-0.86, p < 0.001), breast (aPR = 0.83, CI = 0.68-0.99, p = 0.045), and colorectal cancer (aPR = 0.55, CI = 0.44-0.68, p < 0.001), as compared to Chinese respondents. Respondents who had obtained lower secondary level education were 42% more likely to screen for cervical cancer (aPR = 1.42, CI = 1.23-1.64, p < 0.001), and 22% more likely to screen for breast cancer (aPR = 1.22, CI = 1.02-1.46, p = 0.032), compared to those with primary level education and below. Respondents with a household income ≥S$10,000/month were 71% more likely to screen for breast cancer (aPR = 1.71, CI = 1.37-2.13, p < 0.001), as compared with <$2,000/month.ConclusionsEthnicity and socio-economic status were significantly associated with lower uptake of cancer screening tests in Singapore. To improve the screening uptake among disadvantaged groups, a multi-faceted approach is needed that addresses the barriers to screening such as the adequacy of subsidy schemes and ethnic differences.

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Project description:IntroductionPopulation-based studies of breast cancer have estimated that some PALB2 mutations confer a breast cancer risk (penetrance) comparable to the average pathogenic mutation in BRCA2. As this risk is of clinical relevance, we sought to identify mono-allelic PALB2 mutations and determine their frequencies in multiple-case breast cancer families attending Familial Cancer Clinics in Australia and New Zealand.MethodsThe youngest affected woman, not known to carry a mutation in BRCA1 or BRCA2, from 747 multiple-case breast cancer families participating in kConFab were selected for PALB2 mutation screening. The coding and flanking intronic regions of PALB2 in DNA extracted from blood were screened using high-resolution melt curve analysis with Sanger sequencing confirmation. Where possible, relatives of women found to carry PALB2 mutations were genotyped for the family-specific mutation, mutant transcripts were characterised and breast tumours arising in mutation carriers were recalled and reviewed. Missense mutations were assessed for potential to disrupt protein function via SIFT, Align GVGD and Polyphen-2.ResultsThe mutation screen identified two nonsense mutations (PALB2 c.3113G>A in eight women and PALB2 c.196C>T in one woman), two frameshift mutations (PALB2 c.1947_1948insA and PALB2 c.2982_2983insT each in one woman), 10 missense variants, eight synonymous variants and four variants in intronic regions. Of the four PALB2 mutations identified that were predicted to produce truncated protein products, only PALB2 c.1947_1948insA had not previously been reported. PALB2 c.3113G>A and PALB2 c.196C>T were previously identified in the Australian population whereas PALB2 c.2982_2983insT was previously reported in the UK population. Transcripts derived from three of these mutant PALB2 alleles were vulnerable to nonsense-mediated decay. One missense mutation (PALB2 c.2993G>A) was predicted to disrupt protein function via the three in silico assessment methods applied. The majority of breast cancers arising in carriers that were available for review were high-grade invasive ductal carcinomas.ConclusionsAbout 1.5% (95% CI 0.6to 2.4) of Australasian multiple-case breast cancer families attending clinics are segregating protein-truncating mutations in PALB2, most being PALB2 c.3113G>A, p.Trp1038*. Given the prevalence, breast cancer risk, and tumour grade associated with this mutation, consideration of clinical PALB2 testing is warranted.

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Dataset Information

Prevalence of PALB2 mutations in breast cancer patients in multi-ethnic Asian population in Malaysia and Singapore.

Background

Methods

Results

Publications

Prevalence of PALB2 mutations in breast cancer patients in multi-ethnic Asian population in Malaysia and Singapore.

Similar Datasets

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