16 research outputs found
Abstract 1294: Prevalence and spectrum of germline rare variants in <i>BRCA1/2</i> and <i>PALB2</i> among breast cancer cases in Sarawak, Malaysia
No full textAbstract
Germline mutations in the BRCA1 and BRCA2 genes result in predisposition to breast and ovarian cancer. Detection of BRCA mutation carriers can lead to improved prevention and therapeutic interventions such as the targeted therapy using poly ADP ribose polymerase (PARP) inhibitors, which are particularly effective in BRCA mutation carriers. The spectrum of BRCA mutations varies depending on geographic origin, population, and ethnic group; however, the prevalence of BRCA mutations in non-Caucasian populations has been poorly characterized, particularly in a population-based setting. The goal of this study was to characterize the spectrum of germline mutations in BRCA1/2 and PALB2 in unselected breast cancer cases who were seen in Sarawak General Hospital, Malaysia, where 93% of the breast cancer patients in Sarawak are treated. We performed targeted sequencing using a validated AmpliSeq panel on 467 cases with available risk factor questionnaire and clinical follow-up data. Breast cancer subtypes were defined by the joint expression of ER, PR, and HER2. Common variants with frequency &gt;1% in any public database (1000 Genome, Exome Sequencing Project, The Exome Aggregation Consortium) were excluded. Pathogenic variants included known pathogenic variants in ClinVar, loss of function variants (frameshift and stop-gain), and variants that alter the first or second base of the splice site. Variants of unknown significance (VUS) were also defined using the ClinVar classification. We found 10 BRCA1 pathogenic variants in 12 patients, 10 BRCA2 pathogenic variants in 15 patients, and 4 PALB2 pathogenic variants in 4 patients, which gave a BRCA mutation prevalence of 5.78% among the unselected breast cancer cases in this population. All these variants were extremely rare in the general population (&lt;0.05%). Only 4 of them were recurrent variants (2 in BRCA1 and 2 in BRCA2) and all four are known variants that were reported previously in other populations. In addition, we identified a novel deleterious mutation (stop-gain) that has never been reported and a number of VUS variants in this population. Patients with pathogenic BRCA and PALB2 variants were associated with an earlier age at onset (7 years younger, p=0.0005), a positive family history (20% higher, p=0.01), and the triple-negative (TN) subtype (56% vs. 18%, p&lt;0.0001), compared to patients without mutations. Mutation carrier cases had worse survival compared to non-carriers, however, the association was mostly driven by the higher frequency of TN in mutation carriers. Our study for the first time reported the prevalence of germline mutations in BRCA and PALB2 in a quasi-population-based case series unselected for age and family history in an under-studied Asian population. Our results may have important clinical implications for performing genetic testing on selected patients in a low-resource setting.
Citation Format: Xiaohong (Rose) Yang, Beena Devi, Hyuna Sung, Jennifer Guida, Yanzi Xiao, Lisa Garland, Nan Hu, Maria Rodriguez-Herrera, Chaoyu Wang, Kristine Jones, Wen Luo, Belynda Hicks, Tieng Swee Tang, Karobi Moitra, Mike Dean. Prevalence and spectrum of germline rare variants in BRCA1/2 and PALB2 among breast cancer cases in Sarawak, Malaysia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1294. doi:10.1158/1538-7445.AM2017-1294</jats:p
Incidence and risk factors for breast cancer subtypes in three distinct South-East Asian ethnic groups: Chinese, Malay and natives of Sarawak, Malaysia
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Breast cancer risk factors, survival and recurrence, and tumor molecular subtype: analysis of 3012 women from an indigenous Asian population
No full textAbstract Background Limited evidence, mostly from studies in Western populations, suggests that the prognostic effects of lifestyle-related risk factors may be molecular subtype-dependent. Here, we examined whether pre-diagnostic lifestyle-related risk factors for breast cancer are associated with clinical outcomes by molecular subtype among patients from an understudied Asian population. Methods In this population-based case series, we evaluated breast cancer risk factors in relation to 10-year all-cause mortality (ACM) and 5-year recurrence by molecular subtype among 3012 women with invasive breast cancer in Sarawak, Malaysia. A total of 579 deaths and 314 recurrence events occurred during a median follow-up period of ~ 24 months. Subtypes (luminal A-like, luminal B-like, HER2-enriched, triple-negative) were defined using immunohistochemical markers for hormone receptors and human epidermal growth factor receptor 2 (HER2) in conjunction with histologic grade. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between risk factors and ACM/recurrence were estimated in subtype-specific Cox regression models. Results We observed heterogeneity in the relationships between parity/breastfeeding, age at first full-term pregnancy (FFP), family history, body mass index (BMI), and tumor subtype (p value 30 vs < 21 years = 0.20 (0.04, 0.90)] were associated with good prognosis. For these women, the addition of age at menarche, parity/breastfeeding, and BMI, provided significantly better fit to a prognostic model containing standard clinicopathological factors alone [LRχ2 (8df) = 21.78; p value = 0.005]. Overall, the results were similar in relation to recurrence. Conclusions Our finding that breastfeeding and BMI were associated with prognosis only among women with luminal A-like breast cancer is consistent with those from previously published data in Western populations. Further prospective studies will be needed to clarify the role of lifestyle modification, especially changes in BMI, in improving clinical outcomes for women with luminal A-like breast cancer
Abstract C81: Differences in breast cancer incidence and survival patterns by tumor subtype and ethnicity in Sarawak, Malaysia
No full textAuthor Correction: Increased Serum Hyaluronic Acid and Heparan Sulfate in Dengue Fever: Association with Plasma Leakage and Disease Severity (Scientific Reports, (2017), 7, 1, (46191), 10.1038/srep46191)
No full text10.1038/s41598-021-92487-3Scientific Reports1111334
Author Correction: Highly specific and non-invasive imaging of Piezo1-dependent activity across scales using GenEPi
No full textCorrection to: Nature Communications, published online 19 July 2023 In the original version of this article, the given and family names of Armando Del Rio Hernandez were incorrectly structured. The name was displayed correctly in all versions at the time of publication. In this article the affiliation details for Nordine Helassa were incorrectly given as ‘7. Centre for Cardiovascular Science, Department of Cardiovascular Science and Metabolic Medicine, Institute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.’ but should have been ‘7. Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.’. The original article has been corrected
Prevalence and spectrum of germline rare variants in BRCA1/2 and PALB2 among breast cancer cases in Sarawak, Malaysia
No full textThe language of risk : Self-assessment of nasopharyngeal cancer risk
No full textThe language of risk is a part of medical discourse that lay people have problems understanding. Scientists, doctors and patients speak a different language of risk because they understand risk differently. Scientists talk about risk factors and the likelihood of the disease while patients experience risk at a personal level (Gifford 1986). Scientists estimate level of risk in numbers but doctors and patients translate risk information to the groups that are more likely to be at risk and what signs appear before the onset of illness (Gifford 1986). For doctors and patients, the distinction between risk and cause is blurred (Jasen 2002). Lupton (1995) categorises risk factors as external factors which are beyond one’s control (e.g., family history), and internal factors which are within one’s control (e.g., dietary habits). Patients often have their own understanding of why cancer might develop and why they delay seeking of treatment, which may not align with scientific knowledge (Jasen 2002).
Much of the research on the language of risk in relation to diseases have focused on breast cancer (e.g., Jasen 2002; Lobb et al. 1999). Women also have problems understanding prognostic information delivered by doctors (Lobb et al. 1999). Traditionally it was clinical examinations that confirmed whether one had a disease, but nowadays self-examination is encouraged for early detection. There is a lack of findings on understanding of risk information for nasopharyngeal (nose and throat) cancer which is not common in Western settings. However, nasopharyngeal cancer incidence is high in Asian countries, particularly in China, Indonesia, Vietnam, India and Philippines (Kumar et al. 2019).
In Malaysia, nasopharyngeal cancer incidence is number five, affecting 4% of the population, based on the National Cancer Registry 2012-2016 (Ministry of Health Malaysia 2019). The incidence is high among males (age-standardised incidence rate of 5.2, ranked fifth among cancers) but not among the top 10 cancers for females. The 25-59 years old group (11.3%) is the most susceptible. This cancer is more common among the Chinese males, compared to Malay and Indian males (age-standardised incidence rates of 8.6, 2.7 and 0.6 respectively). Nasopharyngeal cancer incidence is also particularly high among the Bidayuh indigenous group of Sarawak (Devi et al. 2004; Kumar et al. 2019). Hence, studies on self-assessment of risk factors and potential signs of the cancer are needed.
The preliminary study on nose and throat cancer risk involved 101 respondents (55.4% male, 44.6% female). The age distribution is as follows: below 20 (6.9%), 20-39 (61.4%), 40-59 (21.8%), 60 and above (9.9%). There were more Malays (31.7%) and Chinese (38.5%) among the respondents, followed by Others (12.9%), Iban (6.9%), Bidayuh (5.0%), Indian (3%), Orang Ulu (1%) and Kadazandusun (1%). The instrument was a questionnaire on external risk factors (family history, 1 item) and internal risk factors (lifestyle, 3 items), and signs (4 items). Demographic information obtained were gender, age and ethnic background which are linked to nasopharyngeal cancer incidence in Malaysia.
Respondents filled in the questionnaire after they had given consent. Subsequently, the data on risk factors and signs were computed to obtain a nasopharyngeal cancer assessment score. The risk associated with gender, age, ethnic group and signs were weighted for the computation. At the research exposition, the respondents could see the score and the risk level: low, moderate, high. They were also given an interpretation of what the risk score meant in terms of health protective measures.
The results showed an average nasopharyngeal cancer risk score of 10.7 points out of the maximum of 48 points (range: 3-20). When converted to 100%, the average is 22.3% (range: 6.2%-41.7%). This means that on average, the respondents were at low risk of having nasopharyngeal cancer. Pearson correlation tests showed that there was no relationship between the nasopharyngeal cancer risk score and age. The t-test showed that there were also no significant differences between male and female respondents in their cancer risk score. As for ethnic group, the mean scores show some variation: Chinese (24.6%), Bidayuh (24.2%), Malay (22.7%), Iban (22.3%), Others (16.9%), and Indian (13.1%). The Orang Ulu and Kadazandusun were grouped with ‘Others’ category as there was only one respondent each.
Among the lifestyle risk factors, the greatest risk is from consumption of preserved food, followed by exposure to chemicals and smoking. Smoking was a minimal risk factor for the respondents. A small percentage (0.8%) were non-smokers, 95% reported that they rarely smoked and 1% smoked one to three cigarettes per month and 4% smoked more than five cigarettes per day. The respondents were at minimal risk to nasopharyngeal cancer due to exposure to hazardous chemicals (no exposure, 86.1%; exposure, 13.9%). However, this group was at greater risk due to their consumption of preserved food (never, 2%; one to two times per year, 20.8%; one to two times per month, 54.5%; once per week, 22.8%).
Nasopharyngeal cancer risk from family history was generally low for the respondents. The results showed that 91.1% did not have a family history of the cancer, while 6.9% had one uncle or aunt, and 2% had one parent who contracted the cancer.
The results on the four early signs of nasopharyngeal cancer are as follows, arranged in the order of progressively more certain signs of the cancer:
(1) Symptoms of common cold or flu, such as sore throat, cough, and running nose: less than 2 times per year, 43.6%; 3-5 times per year, 39.6%, 3 times per month, 16.8%;
(2) Ear pain: nul incidence, 78.2%; occasional incidence, 19.8%; frequent incidence, 2%.
(3) Blood in sputum or nasal discharge: nul incidence, 82.2%; occasional incidence, 16.8%; whenever they coughed, 1%.
(4) Lump in neck area: absence, 98%; presence, 2%.
The small percentage who reported blood in their sputum or nasal discharge and a lump in the neck area may be at risk of nasopharyngeal cancer. Taken together, about one-quarter of the respondents self-reported presence of lifestyle risk factors, family history and nasopharyngeal cancer signs (25% Indian respondents, 20.7% Malay respondents, 23.7% Chinese respondents).
In conclusion, our results showed that respondents could perform self-assessment of cancer risk if the ‘diagnostic questions’ were phrased in everyday language and about tangible matters. In our study, we showed the nasopharyngeal cancer risk score in numerical form to respondents because this kind of information appears scientific. However, to help them understand the language of risk, we worded the ‘diagnostic outcome’ as low, moderate and high risk. For example, the high-risk respondents were told, ‘NasoCRA indicates a moderate to high NPC risk. We strongly suggest that you seek medical assistance from relevant medical specialist(s) as soon as possible to get further professional advice, and proper diagnosis. It is necessary that you consider quarterly to half yearly medical check-up’. The findings suggest that to help the lay person understand the language of risk, it is important to provide the risk information in both numerical and text form, and to focus the information on health measures within their control.
References
Devi, Beena C., Pisani, Paola, Tang, Tieng Swee., & Parkin, D. Maxwell. 2004. ‘High incidence of nasopharyngeal carcinoma in native people of Sarawak, Borneo Island,’ Cancer Epidemiology and Prevention Biomarkers 13(3), 482-486.
Gifford, Sandra M. 1986. ‘The meaning of lumps: A case study of the ambiguities of risk,’ in C. R. Janes, Ron Stall, & Sandra M. Gifford, eds., Anthropology and epidemiology: Interdisciplinary approaches to the study of health and illness, 217-230. Dordrecht.
Jasen, Patricia. 2002. Breast cancer and the language of risk, 1750-1950. The Society for the Social History of Medicine, 15(1), 17-43.
Kumar, Karen Michell Othaya, & Mydin, Rabiatul Basria S. M. N. 2019. ‘Nasopharyngeal cancer: Geographic variation and risk factors,’ Malaysian Journal of Medicine and Health Sciences 15(109), 116-121.
Lobb, Elizabeth A., Butow, Phyllis N., Kenny Dianna T., & Tattersall, Martin H. N. 1999. ‘Communicating prognosis in early breast cancer: Do women understand the language used?’ Medical Journal of Australia 171(6), 290-294.
Lupton, Deborah. 1995. ‘The imperative of health: Public health and the regulated body,’ London.
Ministry of Health Malaysia. 2019. Malaysia National Cancer Registry Report (MNCR) 2012-2016, Ministry of Health, Kuala Lumpur.ng Kong: Linguistic Society of Hong Kong
