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  1. Mohd Taib NA, Yip CH, Mohamed I
    Asian Pac. J. Cancer Prev., 2008 Apr-Jun;9(2):197-202.
    PMID: 18712958
    BACKGROUND: Breast cancer is the commonest cancer amongst Malaysian women but local survival data are scarce. The present study was therefore conducted to assess overall survival and prognostic factors in Malaysian breast cancer patients.

    METHODS: The research sample was a prospective cohort of 413 patients diagnosed with breast cancer in the University of Malaya Medical Centre between 1993 to 1997. Survival data were obtained from the National Registry of Birth and Deaths in December 2000. The clinico-pathological variables studied were age, ethnic group, stage, tumour size, lymph node status, oestrogen receptor status and grade. The data were analysed utilizing Splus statistical software. The important prognostic factors were identified by fitting the Cox's proportional hazard model to the data set. Survival probabilities were estimated using the Kaplan-Meier method and differences were compared by the log-rank test.

    RESULTS: The overall 5-year survival was 59.1%. The Cox's proportional hazard model identified stage, lymph node status, size and grade as factors that correlated with prognosis. Age was not a significant prognostic factor. The Cox regression model by stepwise selection showed stage, nodal status and grade of tumour to be independent prognostic factors, whereas ethnicity, age and ER status were not.

    INTERPRETATION: The overall survival in our centre was low. Recognizing factors that affect prognosis of breast cancer patients in Malaysia may improve delivery of health care to at-risk groups by strategizing interventions as survival depends on early detection and effective treatment.
  2. Yip CH, bt Mohd Taib NA, Lau PC
    Asian Pac. J. Cancer Prev., 2008 Jan-Mar;9(1):63-5.
    PMID: 18439076
    INTRODUCTION: An important risk factor for developing breast cancer is a positive family history of breast cancer. In Malaysia, there is no population-based breast screening programme, but the clinical practice guidelines suggest increased surveillance for those with a positive family history ie mammography for those 40 years old and above, breast self-examination and clinical breast examination yearly.
    OBJECTIVE: To determine if women with a family history of breast cancer present with earlier stages of disease.
    METHODOLOGY: From Jan 2001 to Dec 2006, 1553 women with breast cancer presenting to the University Malaya, where family history was recorded, were eligible for this study. Women with a first or second degree relative with breast cancer were compared with those who have no family history with regard to their race, age, stage, size and duration of symptoms. The Chi Square test of significance was used for analysis.
    RESULTS: Out of 1553 patients, 252 (16.2%) were found to have a relative with breast cancer out of which 174 (11.2%) had at least one affected first degree relative. There were no significant difference in the incidence of positive family history between the Malays, Chinese and Indians. 20% below the age of 40 years old had a positive family history compared with 12.6% in women with no family history. (p<0.05). There was no significant difference in stage at diagnosis between those with and without family history, ie 24.2% late stages (Stage 3 and 4) in the group with no family history compared with 21.8% in the group with family history. (p>0.05). The mean size in the group with no family history was 4.4 cm compared to 4.1 cm in the group with family history. There was a significant difference in screen-detected cancers in the women with family history, 10.7% compared with 5.1% of screen-detected cancers in the group without a family history. However there was no difference in the duration of symptoms between the 2 groups--25.8% in the women without a family history presented after 1 year of symptoms compared with 22.4% in the group with a family history (p>0.05).
    CONCLUSION: Having a family history of breast cancer does not appear to have much impact on the health-seeking behavior of women. Even though there were more screen detected cancers, these comprised only 10% of the group with family history. Public education should target women at risk ie with family history to encourage these women to present earlier and to undergo screening for breast cancer.
  3. Baskaran P, Subramanian P, Rahman RA, Ping WL, Mohd Taib NA, Rosli R
    Asian Pac. J. Cancer Prev., 2013;14(12):7693-9.
    PMID: 24460355
    AIMS: A main reason for increasing incidence of cervical cancer worldwide is the lack of regular cervical cancer screening. Coverage and uptake remain major challenges and it is crucial to determine the perceived susceptibility to cervical cancer, as well as the benefits of, and barriers to, cervical cancer screening among women.

    MATERIALS AND METHODS: A cross-sectional survey was conducted among 369 women attending an outpatient centre in Malaysia and data were collected by administering a self-report questionnaire.

    RESULTS: The majority of the participants (265, 71.8%) showed good level of perception of their susceptibility to cervical cancer. Almost all responded positively to four statements about the perceived benefits of cervical cancer screening (agree, 23.1% or strongly agree, 52.5%), whereas negative responses were received from most of the participants (agree, 29.9%or strongly agree, 14.6 %) about the eleven statements on perceived barriers. Significant associations were observed between age and perceived susceptibility(x2=9.030, p=0.029); between employment status (p<0.001) as well as ethnicity and perceived benefits (p<0.05 [P=0.003]); and between education and perceived barriers to cervical cancer screening (p<0.001).

    CONCLUSIONS: Perceived susceptibility, including knowledge levels and personal risk assessment, should be emphasized through education and awareness campaigns to improve uptake of cervical cancer screening in Malaysia.
  4. Ng PS, Wen WX, Fadlullah MZ, Yoon SY, Lee SY, Thong MK, et al.
    Clin. Genet., 2016 10;90(4):315-23.
    PMID: 26757417 DOI: 10.1111/cge.12735
    Although an association between protein-truncating variants and breast cancer risk has been established for 11 genes, only alterations in BRCA1, BRCA2, TP53 and PALB2 have been reported in Asian populations. Given that the age of onset of breast cancer is lower in Asians, it is estimated that inherited predisposition to breast cancer may be more significant. To determine the potential utility of panel testing, we investigated the prevalence of germline alterations in 11 established and 4 likely breast cancer genes in a cross-sectional hospital-based cohort of 108 moderate to high-risk breast cancer patients using targeted next generation sequencing. Twenty patients (19%) were identified to carry deleterious mutations, of whom 13 (12%) were in the BRCA1 or BRCA2, 6 (6%) were in five other known breast cancer predisposition genes and 1 patient had a mutation in both BRCA2 and BARD1. Our study shows that BRCA1 and BRCA2 account for the majority of genetic predisposition to breast cancer in our cohort of Asian women. Although mutations in other known breast cancer genes are found, the functional significance and breast cancer risk have not yet been determined, thus limiting the clinical utility of panel testing in Asian populations.
  5. Lai KN, Ho WK, Kang IN, Kang PC, Phuah SY, Mariapun S, et al.
    BMC Cancer, 2017 02 22;17(1):149.
    PMID: 28222693 DOI: 10.1186/s12885-017-3099-6
    BACKGROUND: Genetic testing for BRCA1 and BRCA2 has led to the accurate identification of individuals at higher risk of cancer and the development of new therapies. Approximately 10-20% of the genetic testing for BRCA1 and BRCA2 leads to the identification of variants of uncertain significance (VUS), with higher proportions in Asians. We investigated the functional significance of 7 BRCA1 and 25 BRCA2 variants in a multi-ethnic Asian cohort using a case-control approach.

    METHODS: The MassARRAY genotyping was conducted in 1,394 Chinese, 406 Malay and 310 Indian breast cancer cases and 1,071 Chinese, 167 Malay and 255 Indian healthy controls. The association of individual variant with breast cancer risk was analyzed using logistic regression model adjusted for ethnicity, age and family history.

    RESULTS: Our study confirmed BRCA2 p.Ile3412Val is presented in >2% of unaffected women and is likely benign, and BRCA2 p.Ala1996Thr which is predicted to be likely pathogenic by in-silico models is presented in 2% of healthy Indian women suggesting that it may not be associated with breast cancer risk. Single-variant analysis suggests that BRCA1 p.Arg762Ser may be associated with breast cancer risk (OR = 7.4; 95% CI, 0.9-62.3; p = 0.06).

    CONCLUSIONS: Our study shows that BRCA2 p.Ile3412Val and p.Ala1996Thr are likely benign and highlights the need for population-specific studies to determine the likely functional significance of population-specific variants. Our study also suggests that BRCA1 p.Arg762Ser may be associated with increased risk of breast cancer but other methods or larger studies are required to determine a more precise estimate of breast cancer risk.

  6. Mohd Mujar NM, Dahlui M, Emran NA, Abdul Hadi I, Wai YY, Arulanantham S, et al.
    PLoS ONE, 2017;12(4):e0176394.
    PMID: 28448541 DOI: 10.1371/journal.pone.0176394
    Complementary and alternative medicine (CAM) is widely used among the breast cancer patients in Malaysia. Delays in presentation, diagnosis and treatment have been shown to impact the disease prognosis. There is considerable use of CAM amongst breast cancer patients. CAM use has been cited as a cause of delay in diagnosis and treatments in qualitative studies, however there had not been any confirmatory study that confirms its impact on delays. The purpose of this study was to evaluate whether the use of CAM among newly diagnosed breast cancer patients was associated with delays in presentation, diagnosis or treatment of breast cancer. This multi-centre cross-sectional study evaluating the time points of the individual breast cancer patients' journey from first visit, resolution of diagnosis and treatments was conducted in six public hospitals in Malaysia. All newly diagnosed breast cancer patients from 1st January to 31st December 2012 were recruited. Data were collected through medical records review and patient interview by using a structured questionnaire. Complementary and alternative medicine (CAM) was defined as the use of any methods and products not included in conventional allopathic medicine before commencement of treatments. Presentation delay was defined as time taken from symptom discovery to first presentation of more than 3 months. The time points were categorised to diagnosis delay was defined as time taken from first presentation to diagnosis of more than 1 month and treatment delay was defined as time taken from diagnosis to initial treatment of more than 1 month. Multiple logistic regression was used for analysis. A total number of 340 patients participated in this study. The prevalence of CAM use was 46.5% (n = 158). Malay ethnicity (OR 3.32; 95% CI: 1.85, 5.97) and not interpreting symptom as cancerous (OR 1.79; 95% CI: 1.10, 2.92) were significantly associated with CAM use. The use of CAM was associated with delays in presentation (OR 1.65; 95% CI: 1.05, 2.59), diagnosis (OR 2.42; 95% CI: 1.56, 3.77) and treatment of breast cancer (OR 1.74; 95% CI: 1.11, 2.72) on univariate analyses. However, after adjusting with other covariates, CAM use was associated with delays in presentation (OR 1.71; 95% CI: 1.05, 2.78) and diagnosis (OR 2.58; 95% CI: 1.59, 4.17) but not for treatment of breast cancer (OR 1.58; 95% CI: 0.98, 2.55). The prevalence of CAM use among the breast cancer patients was high. Women of Malay ethnicity and not interpreting symptom as cancerous were significantly associated with CAM use. The use of CAM is significantly associated with delay in presentation and resolution of diagnosis. This study suggests further evaluation of access to breast cancer care is needed as poor access may cause the use of CAM. However, since public hospitals in Malaysia are heavily subsidized and readily available to the population, CAM use may impact delays in presentation and diagnosis.
  7. Zulkipli AF, Islam T, Mohd Taib NA, Dahlui M, Bhoo-Pathy N, Al-Sadat N, et al.
    Integr Cancer Ther, 2018 06;17(2):312-321.
    PMID: 29218996 DOI: 10.1177/1534735417745248
    BACKGROUND: The use of complementary and alternative medicine (CAM) has increased and little is known on CAM use during the initial period. Therefore, the aim was to determine prevalence of CAM use among newly diagnosed breast cancer patients prior to seeking conventional treatment.

    METHODS: This is a cross-sectional study involved interviewing newly diagnosed breast cancer patients in the University Malaya Medical Centre (UMMC) using a structured questionnaire. Eligible respondents were interviewedduring a routine clinical visit.

    RESULTS: A total of 400 patients were interviewed, of whom 139 (34.8%) were CAM users. Dietary supplementation (n = 107, 77.0%) was the most frequently used type of CAM, followed by spiritual healing (n = 40, 28.8%) and traditional Chinese medicine (n = 32, 23.0%). Malay ethnic group (n = 61, 43.9%) was the largest group of CAM users, followed by Chinese (n = 57, 41.0%) and Indian (n = 20, 14.4%). Majority of these CAM users (n = 87, 73.1%) did not disclose the use of CAM to their doctors. Most of them used remedies based on the recommendation of family and friends. Malay ethnicity and patients with 3 or more comorbidities were more likely to use CAM.

    CONCLUSION: There is substantial use of CAM among breast cancer patients in UMMC prior to seeking hospital treatment, and the most popular CAM modality is dietary supplements. Since, the majority of CAM users do not disclose the use of CAM to their physicians, therefore health care providers should ensure that those patients who are likely to use CAM are appropriately counseled and advised.

  8. Lim KK, Yoon SY, Mohd Taib NA, Shabaruddin FH, Dahlui M, Woo YL, et al.
    Appl Health Econ Health Policy, 2018 06;16(3):395-406.
    PMID: 29572724 DOI: 10.1007/s40258-018-0384-8
    OBJECTIVE: Previous studies showed that offering BRCA mutation testing to population subgroups at high risk of harbouring the mutation may be cost effective, yet no evidence is available for low- or middle-income countries (LMIC) and in Asia. We estimated the cost effectiveness of BRCA mutation testing in early-stage breast cancer patients with high pre-test probability of harbouring the mutation in Malaysia, an LMIC in Asia.

    METHODS: We developed a decision analytic model to estimate the lifetime costs and quality-adjusted life-years (QALYs) accrued through BRCA mutation testing or routine clinical surveillance (RCS) for a hypothetical cohort of 1000 early-stage breast cancer patients aged 40 years. In the model, patients would decide whether to accept testing and to undertake risk-reducing mastectomy, oophorectomy, tamoxifen, combinations or neither. We calculated the incremental cost-effectiveness ratio (ICER) from the health system perspective. A series of sensitivity analyses were performed.

    RESULTS: In the base case, testing generated 11.2 QALYs over the lifetime and cost US$4815 per patient whereas RCS generated 11.1 QALYs and cost US$4574 per patient. The ICER of US$2725/QALY was below the cost-effective thresholds. The ICER was sensitive to the discounting of cost, cost of BRCA mutation testing and utility of being risk-free, but the ICERs remained below the thresholds. Probabilistic sensitivity analysis showed that at a threshold of US$9500/QALY, 99.9% of simulations favoured BRCA mutation testing over RCS.

    CONCLUSIONS: Offering BRCA mutation testing to early-stage breast cancer patients identified using a locally-validated risk-assessment tool may be cost effective compared to RCS in Malaysia.

  9. Soh WH, Rajaram N, Mariapun S, Eriksson M, Fadzli F, Ho WK, et al.
    Cancer Causes Control, 2018 Sep;29(9):883-894.
    PMID: 30062608 DOI: 10.1007/s10552-018-1064-6
    BACKGROUND: Physical activity is a modifiable lifestyle factor associated with reduced breast cancer risk. Mammographic density is a strong, independent risk factor for breast cancer, and some breast cancer risk factors have been shown to modify mammographic density. However, the effect of physical activity on mammographic density, studied predominantly among Caucasians, has yielded conflicting results. In this study, we examined, in an Asian population, the association between physical activity and mammographic density.

    METHODS: We conducted a cross-sectional study of 2,377 Malaysian women aged 40-74 years. Physical activity information was obtained at screening mammogram and mammographic density was measured from mammograms by the area-based STRATUS method (n = 1,522) and the volumetric Volpara™ (n = 1,200) method. Linear regression analyses were performed to evaluate the association between physical activity and mammographic density, adjusting for potential confounders.

    RESULTS: We observed that recent physical activity was associated with area-based mammographic density measures among postmenopausal women, but not premenopausal women. In the fully adjusted model, postmenopausal women with the highest level of recent physical activity had 8.0 cm2 [95% confidence interval: 1.3, 14.3 cm2] lower non-dense area and 3.1% [0.1, 6.3%] higher area-based percent density, compared to women with the lowest level of recent physical activity. Physical activity was not associated to volumetric mammographic density.

    CONCLUSIONS: Our findings suggest that the beneficial effects of physical activity on breast cancer risk may not be measurable through mammographic density. Future research is needed to identify appropriate biomarkers to assess the effect of physical activity on breast cancer risk.

  10. Wen WX, Soo JS, Kwan PY, Hong E, Khang TF, Mariapun S, et al.
    Breast Cancer Res., 2016 05 27;18(1):56.
    PMID: 27233495 DOI: 10.1186/s13058-016-0717-1
    BACKGROUND: APOBEC3B is a cytosine deaminase implicated in immune response to viral infection, cancer predisposition and carcinogenesis. Germline APOBEC3B deletion is more common in East Asian women and confers a modest risk to breast cancer in both East Asian and Caucasian women. Analysis of tumour samples from women of European descent has shown that germline APOBEC3B deletion is associated with an increased propensity to develop somatic mutations and with an enrichment for immune response-related gene sets. However, this has not been examined in Asian tumour samples, where population differences in genetic and dietary factors may have an impact on the immune system.

    METHODS: In this study, we determined the prevalence of germline APOBEC3B deletion and its association with breast cancer risk in a cross-sectional hospital-based Asian multi-ethnic cohort of 1451 cases and 1442 controls from Malaysia. We compared gene expression profiles of breast cancers arising from APOBEC3B deletion carriers and non-carriers using microarray analyses. Finally, we characterised the overall abundance of tumour-infiltrating immune cells in breast cancers from TCGA and METABRIC using ESTIMATE and relative frequency of 22 immune cell subsets in breast cancers from METABRIC using CIBERSORT.

    RESULTS: The minor allelic frequency of APOBEC3B deletion was estimated to be 0.35, 0.42 and 0.16 in female populations of Chinese, Malay and Indian descent, respectively, and that germline APOBEC3B deletion was associated with breast cancer risk with odds ratios of 1.23 (95 % CI: [1.05, 1.44]) for one-copy deletion and 1.38 (95 % CI: [1.10, 1.74]) for two-copy deletion compared to women with no deletion. Germline APOBEC3B deletion was not associated with any clinicopathologic features or the expression of any APOBEC family members but was associated with immune response-related gene sets (FDR q values 

  11. Kang P, Mariapun S, Phuah SY, Lim LS, Liu J, Yoon SY, et al.
    Breast Cancer Res. Treat., 2010 Nov;124(2):579-84.
    PMID: 20617377 DOI: 10.1007/s10549-010-1018-5
    Early studies of genetic predisposition due to the BRCA1 and BRCA2 genes have focused largely on sequence alterations, but it has now emerged that 4-28% of inherited mutations in the BRCA genes may be due to large genomic rearrangements of these genes. However, to date, there have been relatively few studies of large genomic rearrangements in Asian populations. We have conducted a full sequencing and large genomic rearrangement analysis (using Multiplex Ligation-dependent Probe Amplification, MLPA) of 324 breast cancer patients who were selected from a multi-ethnic hospital-based cohort on the basis of age of onset of breast cancer and/or family history. Three unrelated individuals were found to have large genomic rearrangements: 2 in BRCA1 and 1 in BRCA2, which accounts for 2/24 (8%) of the total mutations detected in BRCA1 and 1/23 (4%) of the mutations in BRCA2 detected in this cohort. Notably, the family history of the individuals with these mutations is largely unremarkable suggesting that family history alone is a poor predictor of mutation status in Asian families. In conclusion, this study in a multi-ethnic (Malay, Chinese, Indian) cohort suggests that large genomic rearrangements are present at a low frequency but should nonetheless be included in the routine testing for BRCA1 and BRCA2.
  12. Mohamed E, Abdul-Rahman PS, Doustjalali SR, Chen Y, Lim BK, Omar SZ, et al.
    Electrophoresis, 2008 Jun;29(12):2645-50.
    PMID: 18494030 DOI: 10.1002/elps.200700828
    A 35 kDa glycoprotein whose abundance was previously demonstrated to be enhanced in sera of patients with endometrial adenocarcinoma (n = 12), was isolated from pooled sera of three of the cancer patients using champedak galactose-binding lectin affinity chromatography in the present study. Subjecting it to 2-DE and MS/MS, the glycoprotein was identified as the O-glycosylated fragment of inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4). When compared to control sera (n = 17), expression of the 35 kDa ITIH4 cleavage fragment was demonstrated to be significantly enhanced in sera of patients with breast carcinoma (n = 10), epithelial ovarian carcinoma (n = 10), and germ cell ovarian carcinoma (n = 10) but not in patients with nasopharyngeal carcinoma (n = 13) and osteosarcoma (n = 7). The lectin-based electrophoretic bioanalytical method adopted in the present study may be used to assess the physiological relevance of ITIH4 fragmentation and its correlation with different malignancies, their stages and progression.
  13. Toh GT, Kang P, Lee SS, Lee DS, Lee SY, Selamat S, et al.
    PLoS ONE, 2008;3(4):e2024.
    PMID: 18431501 DOI: 10.1371/journal.pone.0002024
    BACKGROUND: In Asia, breast cancer is characterised by an early age of onset: In Malaysia, approximately 50% of cases occur in women under the age of 50 years. A proportion of these cases may be attributable, at least in part, to genetic components, but to date, the contribution of genetic components to breast cancer in many of Malaysia's ethnic groups has not been well-characterised.
    METHODOLOGY: Given that hereditary breast carcinoma is primarily due to germline mutations in one of two breast cancer susceptibility genes, BRCA1 and BRCA2, we have characterised the spectrum of BRCA mutations in a cohort of 37 individuals with early-onset disease (
  14. Lee DS, Yoon SY, Looi LM, Kang P, Kang IN, Sivanandan K, et al.
    Breast Cancer Res., 2012;14(2):R66.
    PMID: 22507745
    Germline TP53 mutations cause an increased risk to early-onset breast cancer in Li-Fraumeni syndrome (LFS) families and the majority of carriers identified through breast cancer cohorts have LFS or Li-Fraumeni-like (LFL) features. However, in Asia and in many low resource settings, it is challenging to obtain accurate family history and we, therefore, sought to determine whether the presence of early-onset breast cancer is an appropriate selection criteria for germline TP53 testing.
  15. Rajaram N, Lim ZY, Song CV, Kaur R, Mohd Taib NA, Muhamad M, et al.
    Psychooncology, 2019 Jan;28(1):147-153.
    PMID: 30346074 DOI: 10.1002/pon.4924
    OBJECTIVES: Patient-reported outcomes (PROs) in high-income countries (HICs) suggest that physical, emotional, and psychological needs are important in cancer care. To date, there have been few inconsistent descriptions of PROs in low-income and middle-income Asian countries. Using a standard questionnaire developed by the International Consortium for Health Outcomes Measurement (ICHOM), we compared the perceived importance of PROs between patients in Malaysia and those in HICs and between clusters of Malaysian women.

    METHODS: Breast cancer patients were recruited from three Malaysian hospitals between June and November 2017. We compared the proportion of patients who rated PROs as very important (scored 7-9 on a 9-point Likert scale) between Malaysian patients and data collected from patients in HICs via the ICHOM questionnaire development process, using logistic regression. A two-step cluster analysis explored differences in PROs among Malaysian patients.

    RESULTS: The most important PROs for both cohorts were survival, overall well-being, and physical functioning. Compared with HIC patients (n = 1177), Malaysian patients (n = 969) were less likely to rate emotional (78% vs 90%), cognitive (76% vs 84%), social (72% vs 81%), and sexual (30% vs 56%) functioning as very important outcomes (P 

  16. Kang PC, Phuah SY, Sivanandan K, Kang IN, Thirthagiri E, Liu JJ, et al.
    Breast Cancer Res. Treat., 2014 Apr;144(3):635-42.
    PMID: 24578176 DOI: 10.1007/s10549-014-2894-x
    Although the breast cancer predisposition genes BRCA1 and BRCA2 were discovered more than 20 years ago, there remains a gap in the availability of genetic counselling and genetic testing in Asian countries because of cost, access and inaccurate reporting of family history of cancer. In order to improve access to testing, we developed a rapid test for recurrent mutations in our Asian populations. In this study, we designed a genotyping assay with 55 BRCA1 and 44 BRCA2 mutations previously identified in Asian studies, and validated this assay in 267 individuals who had previously been tested by full sequencing. We tested the prevalence of these mutations in additional breast cancer cases. Using this genotyping approach, we analysed recurrent mutations in 533 Malaysian breast cancer cases with <10 % a priori risk, and found 1 BRCA1 (0.2 %) and 5 BRCA2 (0.9 %) carriers. Testing in a hospital-based unselected cohort of 532 Singaporean breast cancer cases revealed 6 BRCA1 (1.1 %) and 3 BRCA2 (0.6 %) carriers. Overall, 2 recurrent BRCA1 and 1 BRCA2 mutations in Malays, 3 BRCA1 and 2 BRCA2 mutations in Chinese and 1 BRCA1 mutation in Indians account for 60, 24 and 20 % of carrier families, respectively. By contrast, haplotype analyses suggest that a recurrent BRCA2 mutation (c.262_263delCT) found in 5 unrelated Malay families has at least 3 distinct haplotypes. Taken together, our data suggests that panel testing may help to identify carriers, particularly Asian BRCA2 carriers, who do not present with a priori strong family history characteristics.
  17. Wen WX, Allen J, Lai KN, Mariapun S, Hasan SN, Ng PS, et al.
    J. Med. Genet., 2018 02;55(2):97-103.
    PMID: 28993434 DOI: 10.1136/jmedgenet-2017-104947
    BACKGROUND: Genetic testing for BRCA1 and BRCA2 is offered typically to selected women based on age of onset and family history of cancer. However, current internationally accepted genetic testing referral guidelines are built mostly on data from cancer genetics clinics in women of European descent. To evaluate the appropriateness of such guidelines in Asians, we have determined the prevalence of germ line variants in an unselected cohort of Asian patients with breast cancer and healthy controls.

    METHODS: Germ line DNA from a hospital-based study of 2575 unselected patients with breast cancer and 2809 healthy controls were subjected to amplicon-based targeted sequencing of exonic and proximal splice site junction regions of BRCA1 and BRCA2 using the Fluidigm Access Array system, with sequencing conducted on a Illumina HiSeq2500 platform. Variant calling was performed with GATK UnifiedGenotyper and were validated by Sanger sequencing.

    RESULTS: Fifty-five (2.1%) BRCA1 and 66 (2.6%) BRCA2 deleterious mutations were identified among patients with breast cancer and five (0.18%) BRCA1 and six (0.21%) BRCA2 mutations among controls. One thousand one hundred and eighty-six (46%) patients and 97 (80%) carriers fulfilled the National Comprehensive Cancer Network guidelines for genetic testing.

    CONCLUSION: Five per cent of unselected Asian patients with breast cancer carry deleterious variants in BRCA1 or BRCA2. While current referral guidelines identified the majority of carriers, one in two patients would be referred for genetic services. Given that such services are largely unavailable in majority of low-resource settings in Asia, our study highlights the need for more efficient guidelines to identify at-risk individuals in Asia.

  18. Tan MM, Ho WK, Yoon SY, Mariapun S, Hasan SN, Lee DS, et al.
    PLoS ONE, 2018;13(9):e0203469.
    PMID: 30216346 DOI: 10.1371/journal.pone.0203469
    BACKGROUND: Breast cancer risk factors have been examined extensively in Western setting and more developed Asian cities/countries. However, there are limited data on developing Asian countries. The purpose of this study was to examine breast cancer risk factors and the change of selected risk factors across birth cohorts in Malaysian women.

    METHODS: An unmatched hospital based case-control study was conducted from October 2002 to December 2016 in Selangor, Malaysia. A total of 3,683 cases and 3,980 controls were included in this study. Unconditional logistic regressions, adjusted for potential confounding factors, were conducted. The breast cancer risk factors were compared across four birth cohorts by ethnicity.

    RESULTS: Ever breastfed, longer breastfeeding duration, a higher soymilk and soy product intake, and a higher level of physical activity were associated with lower risk of breast cancer. Chinese had the lowest breastfeeding rate, shortest breastfeeding duration, lowest parity and highest age of first full term pregnancy.

    CONCLUSIONS: Our study shows that breastfeeding, soy intake and physical activity are modifiable risk factors for breast cancer. With the increasing incidence of breast cancer there is an urgent need to educate the women about lifestyle intervention they can take to reduce their breast cancer risk.

  19. Dörk T, Peterlongo P, Mannermaa A, Bolla MK, Wang Q, Dennis J, et al.
    Sci Rep, 2019 Aug 29;9(1):12524.
    PMID: 31467304 DOI: 10.1038/s41598-019-48804-y
    Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
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