Malay Patients Research Articles

The impact of bilateral or unilateral cataract surgery on visual functioning: when does second eye cataract surgery benefit patients?

AimTo examine the impact of bilateral or unilateral cataract surgery on visual functioning.MethodsThe Singapore Malay Eye Study is a population-based study of 3280 Singapore Malay patients aged 40–80 years, of...

Single-Center Experience of von Willebrand Disease (vWD) Among Patients with Menorrhagia: A Diagnosis which could be Missed

Menorrhagia is one of the gynecological complaints, seen in women of reproductive age. In majority of cases no organic pathology is found. To date there is no consensus on application of von Willebrand disease (vWD) testing as part of the routine investigations in menorrhagia. Diagnosis of vWD is challenging. It is complicated by intra-individual variations in von Willebrand antigen, activity, and factor VIII levels due to fluctuation of these factor levels during the menstrual cycle or hormonal therapy. The aim of this study is to detect vWD presenting with menorrhagia among Malays attending gynecology clinic by using a standard panel of haemostatic profiles. Thirty Malay patients attending gynecology clinic with unexplained menorrhagia were included in this study. Haemostatic profile such as platelet count, prothrombin time, activated partial thromboplastin time (APTT), factor VIII assay, von Willebrand factor antigen, and von Willebrand factor activity, and collagen binding assay were measured in all patients. Pre- and post hormonal haemostatic profiles were also performed in the patients diagnosed as vWD. All patients had normal APTT. Based on von Willebrand factor work-up, vWD was diagnosed in four patients (13.3%). Three of them were Type 1 and the other one was Type 2M. Investigation for vWD is essential in patients with menorrhagia and thus the laboratories performing vWD testing should provide a complete panel of diagnostic work-up in order to reduce the interpretation error. Screening for vWD should be performed before hormonal treatment as haemostatic profile post treatment could mask the diagnosis.

P5-14-10: Ethnic Differences in the Association between Tumor Size and Lymph Node Status among Breast Cancer Patients in South East Asia.

Abstract Background: South East Asia consists of three major ethnic groups, i.e. Chinese, Malays and Indians. Previous work from our breast cancer research group showed that Malay ethnicity is an independent predictor of poor survival. In this study we evaluate whether (part of) these ethnic survival disparities may be due to ethnic differences in the association of tumor size and lymph node involvement. Methods: We included all patients diagnosed with breast cancer at the National University Hospital (Singapore) and University of Malaya Medical Center (Kuala Lumpur) between 1990 and 2007, for whom information on tumor size and axillary lymph node status was available (n = 3805). Ethnic differences in the association between tumor size and lymph node involvement were studied and logistic regression analysis was performed to determine the independent effect of ethnicity on the association of tumor size and lymph node involvement. Results: 1474 patients were categorized as T1 (>0 to 2 cm), 1777 as T2 (2.1 to 5 cm) and 554 as T3 (>5 cm). Within the small tumor size range (>0 to 2 cm) the Malays were significantly more likely to present with node positive disease as compared to the other ethnic groups (36.9% as compared to 24.5% for Chinese and 25.9% for Indians, p value <0.001). Similarly, for tumors measuring 2.1-5 cm, Malays were more likely than Chinese and Indians to have lymph node involvement (59.5%, 50.2% and 52.1%, respectively p value 0.016). After adjustment for age, Progesterone Receptor (PR) status, grade and treatment received, Malay ethnicity was an independent predictor of lymph node involvement, with adjusted Odds Ratio's of 1.4 (95% CI 1.0 to 2.1) for T1 tumors and 1.4 (95% CI 1.1 to 1.9) for T2 tumors compared to Chinese women. Conclusion: Malay patients are more likely to present with lymph node metastasis especially for the small and midsized tumors as compared to the Chinese and Indians. This could reflect differences in tumor biology between the three ethnic groups with the Malays possibly having more aggressive disease than the others. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-10.

P2-14-07: Ethnic Differences in Breast Cancer Molecular Subtypes and Survival Outcomes in a Multi-Ethnic Singaporean Population.

Abstract Background: Previous studies have described differences in breast cancer biological subtypes from various ethnic backgrounds such as women of African descent. Data on the heterogeneity of breast cancer biology among Asian ethnic groups is limited. Objectives: The aim of this study was to evaluate the frequency of the different immunohistochemical (IHC) subtypes of breast carcinoma and clinical outcomes among Chinese, Malay and Indian patients (pts) at a single Singaporean institution. Methods: Local pts of Chinese, Malay and Indian ethnicity seen at the National Cancer Centre Singapore (NCCS) and diagnosed with breast cancer from 2001 to 2004 were included in this retrospective study. Tumours were classified using IHC profiles as 1)"Luminal": (ER+ and/or PR+, HER2−), 2) HER2 overexpressing (HER2+ regardless of hormone receptor status) and 3) Triple Negative (TNBC: ER, PR and HER2−). Data was collected on pt and tumor characteristics including stage, grade, body mass index (BMI), treatment received including chemotherapy and endocrine therapy, as well as disease-free survival(DFS) and overall survival(OS). Statistical analysis was performed using PASW statistics version 18. Results: Out of the total of 2,061 pts in this study, 86.6% were Chinese, 8.7% were Malays and 4.7% were Indians. Among pts with fully defined receptor status(n=1,427), Chinese pts were more likely to have “luminal” breast cancer at 57% compared with 45% among Malays (p=0.005) and 50% among Indians (p=0.11, ns). Malay and Indian pts were more likely to have TNBC compared with Chinese pts (25.2% and 25% versus 16.6%, p=0.0082 and 0.027 respectively). The frequency of HER2−overexpressing breast cancer did not differ significantly among the Chinese(26.6%), Malay(30.1%) and Indian pts(25%). A greater proportion of Malay pts presented at more advanced stage of 3 or 4 than Chinese and Indian pts (45.6% vs 32.1% and 31.5%, p<0.001 and 0.01 respectively), and were diagnosed at an earlier age than Chinese and Indians (48.5y vs 52.3y and 52.2y, p<0.001 and 0.05 respectively). The frequency of grade 3 cancers was higher among Malays and Indians compared with Chinese (52.3% and 56.3% vs 42%, p=0.007 and 0.006 respectively), and had higher BMI compared to Chinese pts (26.4 and 26.2 vs 22.8, p<0.001 and <0.001 respectively). Malay pts also had lower 5-yr DFS at 59 % and 5-yr OS at 76% compared with 76%(p=<0.001) and 84%(p=0.04) in Chinese pts. Survival analyses on Indian pts were limited by the small numbers. Full multivariate analyses will be tabulated. Conclusions: There are significant differences in the frequency of various subtypes of breast cancer among the Chinese, Malays and Indians in Singapore. The disparities in survival outcomes between the Chinese and the Malays may be related to more aggressive tumor biology, more advanced stage at diagnosis and host factors such as higher BMI. The full impact of ethnicity on breast carcinogenesis is still unknown but is increasingly relevant with the development of therapies that target specific molecular pathways. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-14-07.

Potential hydrophobic protein markers of breast cancer in Malaysian Chinese, Malay and Indian patients

Breast cancer is a leading cause of worldwide mortality in females. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of these, the Chinese had the most number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was used to identify protein profile changes in cancerous tissues compared with the normal tissues, the tissues were collected from patients of three different ethnicities, i.e. Chinese, Malay and Indian. Ten differentially expressed hydrophobic proteins were identified. We had evaluated the potential of these proteins as biomarker for infiltrating ducal carcinoma (IDC) and the ethnic-specific expression of these proteins was also determined. The data showed that peroxiredoxin-2, heat shock protein 60, protein disulfide isomerase and calreticulin may serve as ethnic-related potential markers for either one or combination of Chinese, Malay and Indian cohorts as their expression levels were significantly high in the cancerous tissues compared to the normal tissues in the ethnic group tested.

Risk factors for lower extremity amputation among patients with diabetes in Singapore

Background Among other risk factors, renal disease and ethnicity have been associated with diabetic lower extremity amputation (LEA) in Western populations. However, little is known about risk factors for LEA among Asian patients. Objective The objective was to assess the proportion of hospitalized patients with diabetes who have a LEA among all hospital patients with diabetes mellitus (DM) and to investigate risk factors for diabetic LEA (especially renal disease and ethnicity) using hospital discharge database. Method A retrospective study of hospital discharge database (2004–2009) was performed to identify patients with DM, LEA and renal disease using the International Statistical Classification of Diseases and Related Health Problems, Ninth Revision, Australian Modification codes. Results Of 44 917 hospitalized patients with DM during the 6 years, 7312 (16.3%) patients had renal disease, and 1457 (3.2%) patients had LEA. DM patients with renal disease had significant higher rates of LEA (7.1%) compared to DM patients without renal disease (2.5%, P<.001). The differences were present for foot (2.7% vs. 1.2%), ankle or leg (2.8% vs. 0.9%), and knee or above amputation (1.6% vs. 0.4%, all P<.001). Malays had the highest rate of diabetic LEA (5.1%), followed by Indians (3.0%), Chinese (3.0%), and others (2.3%, P<.001). In logistic regression analyses, renal disease and ethnicity were significant predictors of diabetic LEA (renal disease: odds ratio 3.2, 95% confidence interval 2.8–3.6; ethnicity: odds ratio, 1.6, Malays vs. Chinese, P<.001; 1.0, Indians vs. Chinese, P=.784) after adjustment for age, gender, and year of discharge. Conclusion DM patients with renal disease and Malay ethnicity had higher rates of LEA in this Asian patient population. Malay patients with DM and diabetic patients with renal disease should be considered as high-risk groups for LEA and therefore screened and monitored systematically.

English

Increase in the prevalence of diabetes worldwide and it becoming an epidemic has resulted in a clinical research shift to the management of diabetes mellitus globally. The study aimed to investigate the socio-demographic differences among diabetes patients with infection incidence. The study was conducted in an urban, governmental hospital in Penang Malaysia. The records of patients, more than and equal to age 18 years, who were admitted with diabetes mellitus&nbsp; between January 1, 2008 and December 31, 2010 were reviewed. Statistical analyses were performed using SPSS version 17&reg;. This study was approved by the hospitals &ldquo;Clinical Research Committee (CRC)&rdquo; as well as &ldquo;Ministry of Health Malaysia (MOH)&rdquo;. During the time period of January 2008 through December 2010, there were total 2174 diabetes patients admitted; 2174 (100%) patients&rsquo; charts were reviewed. Of the total, 1063 (48.9%) were males and the rest, 1111 (51.1%), females. Mean and standard distribution (SD) showed females have less mean age distribution (35.2 &plusmn;4.187 years) as compared to males (37.9&plusmn;5.724 years). A total of 798 (36.7%) had infection exposure before and/or during hospital admission; statistical significance (p&lt;0.001) was found in association of diabetes ketoacidosis (DKA) and infection exposure. Though the rate of hospitalization increased among females, OR showed that males were more likely to get the infection severely as compared to females (1.81 (95%CI 1.1-2.40)&nbsp;p&lt;0.021). Profound ethnic difference is three times more prone to severity rate of infection among Malay diabetic patients as compared to other non-Malays (OR 3.44 (95%CI 1.60-5.68)p&lt;0.001). Further analysis showed that with the age of &ge; 65 years and history of diabetes (mean &plusmn; SD: 27.13 &plusmn; 2.782) average patient utilizes 135.7 days (average) of antibiotic course. Increased and recurrent use of antibiotic was found among Malays; also Malays predominantly experience clinical manifestations (poor glycaemic control) as compared to other ethnics. Every third patient with diabetes mellitus had infectious exposure. &nbsp; Key words:&nbsp;Diabetes mellitus, infections, factors association, clinical management, metabolic disorder, endocrinology.

Shared Epitope Alleles Remain A Risk Factor for Anti-Citrullinated Proteins Antibody (ACPA) – Positive Rheumatoid Arthritis in Three Asian Ethnic Groups

BackgroundTo investigate the associations between HLA-DRB1 shared epitope (SE) alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia.Methods1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA) and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping.ResultsThe proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups.ConclusionThe HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia.

Evaluation of N-(carboxymethyl)lysine and lipid peroxidation in multiethnic Malaysian subjects with type 2 diabetes mellitus

The glycoxidation product, Ne-(carboxymethyl)lysine (CML), is formed during reaction of glucose with protein under oxidative conditions. The aim of the study was to evaluate the levels of the most common glycoxidation product; Ne-(carboxymethyl)lysine (CML) and the most advanced lipoxidation product, malondialdehyde (MDA) in type 2 diabetic Malay, Indian, and Chinese ethnic groups in the Malaysian population. Studies were performed on age-matched Malay, Indian, and Chinese subjects with type 2 diabetes mellitus. Different biochemical parameters including serum levels of CML, MDA, lipid profile, glucose, and hemoglobin A1c (HbA1c) were measured by standard methods. The relationships between circulating CML and lipids, HbA1c, and MDA, were examined. Correlation studies between CML, lipids, HbA1c, and lipid peroxidation were performed. CML and MDA levels were significantly higher in Malay subjects than in Indian or Chinese patients (p <0.005). A significant difference was also observed in the levels of serum total cholesterol and LDL-cholesterol (p <0.05) between the groups in the study. A positive correlation was observed between serum levels of CML and MDA in Malay diabetic patients, but no such correlation was seen in either the Chinese or Indian populations. The results of this study demonstrate that ethnicity affects CML and MDA circulating levels in Malaysian subjects with type 2 diabetes mellitus. Key words: Type 2 diabetes mellitus, Ne-(carboxymethyl) lysine, lipoxidation, multiethnic Malaysian subjects.

HLA-A*11 and novel associations in Malays and Chinese with systemic lupus erythematosus

We investigated the association of the HLA genes in Malaysian patients with systemic lupus erythematosus (SLE) and their associations with the clinical manifestations in 160 SLE patients (99 Chinese and 61 Malays) and 107 healthy control individuals (58 Chinese and 49 Malays) were studied. Sequence specific primer amplification (PCR-SSP) phototyping techniques were used to analyse 25 HLA-A allele groups, 31 HLA-DR allele groups and 9 HLA-DQ allele groups. Appreciable increases in allele frequencies of HLA-A*11, DRB1*0701, DRB1*1601–1606, DRB5*01–02 and DQB1*05, and decrease in HLA-DRB1*1101–1121, 1411, DRB1*1201–3, DRB1*1301–22, DRB3*0101, 0201, 0202, 0203, 0301 and DQB1*0301, 1304 in SLE patients compared with healthy control individuals. However, after Bonferroni correction (pc<0.05) only HLA-A*1101, 1102, DRB5*01–02, DQB1*05, DRB1*1201–3, DRB3*0101, 0201, 0202, 0203, 0301 and DQB1*0301, 0304 remained significant. Allele frequencies of DRB1*0701 and DRB4*0101101, 0102, 0103, DQB1*05, DRB1*1301–22, DRB3*0101, 0201, 0202, 0203, 0301 and DQB1*0301, 0304 were significantly increased in Malay SLE patients compared with healthy control individuals. In contrast, Chinese SLE patients had increased allele frequencies of DRB1*1601–1606, DQB1*05, DRB1*1201–3, DRB3*0101, 0201, 0202, 0203, 0301, DRB3*0101, 0201, 0202, 0203, 0301 and DQB1*0301, 0304 compared with healthy control individuals. HLA-A*6801–02 and DRB1*1601–1606 frequencies appeared elevated in a subset of patients with serositis and DRB1* 0401–1122 frequency was elevated in those displaying neurologic disorder. However, unequivocal evidence of these associations would require investigation of substantially larger cohorts. On the whole, our findings suggest that HLA allele associations with SLE are race specific in Malays and Chinese.

Percutaneous coronary intervention in asians- are there differences in clinical outcome?

BackgroundEthnic differences in clinical outcome after percutaneous coronary intervention (PCI) have been reported. Data within different Asian subpopulations is scarce. We aim to explore the differences in clinical profile and outcome between Chinese, Malay and Indian Asian patients who undergo PCI for coronary artery disease (CAD).MethodsA prospective registry of consecutive patients undergoing PCI from January 2002 to December 2007 at a tertiary care center was analyzed. Primary endpoint was major adverse cardiovascular events (MACE) of myocardial infarction (MI), repeat revascularization and all-cause death at six months.Results7889 patients underwent PCI; 7544 (96%) patients completed follow-up and were included in the analysis (79% males with mean age of 59 years ± 11). There were 5130 (68%) Chinese, 1056 (14%) Malays and 1001 (13.3%) Indian patients. The remaining 357 (4.7%) patients from other minority ethnic groups were excluded from the analysis. The primary end-point occurred in 684 (9.1%) patients at six months. Indians had the highest rates of six month MACE compared to Chinese and Malays (Indians 12% vs. Chinese 8.2% vs. Malays 10.7%; OR 1.55 95%CI 1.24-1.93, p < 0.001). This was contributed by increased rates of MI (Indians 1.9% vs. Chinese 0.9% vs. Malays 1.3%; OR 4.49 95%CI 1.91-10.56 p = 0.001), repeat revascularization (Indians 6.5% vs. Chinese 4.1% vs. Malays 5.1%; OR 1.64 95%CI 1.22-2.21 p = 0.0012) and death (Indians 11.4% vs. Chinese 7.6% vs. Malays 9.9%; OR 1.65 95%CI 1.23-2.20 p = 0.001) amongst Indian patients.ConclusionThese data indicate that ethnic variations in clinical outcome exist following PCI. In particular, Indian patients have higher six month event rates compared to Chinese and Malays. Future studies are warranted to elucidate the underlying mechanisms behind these variations.

Lack of association of ABCB1 haplotypes on five loci with response to treatment in epilepsy

Approximately one third of newly treated epilepsy patients do not respond to antiepileptic drugs (AEDs). Overexpression of P-glycoprotein (P-gp) efflux transporter has been proposed to have a critical role in causing resistance to AEDs. P-gp is a product of the ATP-binding cassette subfamily B member 1 (ABCB1) gene. The purpose of this study was to investigate a possible link between ABCB1 rs3789243 C > T, C1236T, G2677T/A, rs6949448 C > T, and C3435T haplotypes with response to carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in Malaysian epilepsy patients. No ABCB1 haplotype association was found with response to either CBZ or VPA monotherapy in the Chinese, Indian, and Malay patients. C3435 allele carriers of the Indian males with cryptogenic epilepsy were more prone to resistance to either CBZ or VPA than carriers of T allele. Moreover, rs3789243T allele carriers of Malay females with symptomatic epilepsy were more resistant to either CBZ or VPA than C allele carriers. Our findings suggest that the ABCB1 rs3789243 C > T, C1236T, G2677T/A, rs6949448 C > T, and C3435T haplotypes do not contribute to response to AED treatment in epilepsy.

Clinical and epidemiological perspectives of dyspepsia in a multiracial Malaysian population

Dyspepsia is perhaps the most common gastrointestinal disease universally. The prevalence of dyspepsia ranges from 7-40% in population based studies worldwide. These figures vary with definition of dyspepsia used and also with the survey methodology. As with Western studies, functional dyspepsia (FD) predominates in Asia. With a decline in peptic ulcer disease and gastric cancer, the proportion of FD is set to increase further. Studies have shown FD to account for 50-70% of cases of uninvestigated dyspepsia. In Malaysia dyspepsia has been reported in up to 15% of a rural and 25% of an urban population. No racial differences were seen in the rural survey. In the urban survey, Malays and Indians were found to have significantly more dyspepsia than Chinese. No clear explanation can be found for these racial differences. In clinical practice, Malays seem to complain a lot of wind and bloating in the "stomach." This is interesting to note when you compare it with the prevalence of H. pylori which is distinctly less common amongst Malays compared to the Indians and Chinese. As with many Asian populations, many Malaysians do not consult for complains of dyspepsia. Many will self medicate and others may even bear with their complains. This is probably true in the rural population. Traditional medications are often used and these are often ethnic based. Different types of lotions for example are used for massaging the putative area in the abdomen by Malay, Chinese and Indian patients. Moxibustion and acupuncture is still practiced by Chinese traditional physicians for treatment of dyspepsia. The notion that mood disorders may underlies dyspepsia is still poorly accepted by a less educated or rural population who consider a psychiatric consultation a taboo. Amongst urban dwellers where Westernized medical care is readily available and the awareness of potential serious disease like cancer is higher, consultation for dyspepsia is certainly higher. Indeed a higher education level has been identified as independent risk factors for dyspepsia in both an urban and rural population survey in Malaysia. With greater consultation for dyspepsia, there has also been a higher demand and utilization of endoscopy services for investigation of gastrointestinal diseases in the country.

Lack of association of ABCB1 and PXR polymorphisms with response to treatment in epilepsy

It is proposed that overexpression of P-glycoprotein (P-gp), encoded by the ABC subfamily B member 1 (ABCB1) gene, is involved in resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation and haplotype patterns are population specific which may cause different phenotypes such as response to AEDs. Although several studies examined the link between the common polymorphisms in the ABCB1 gene with resistance to AEDs, the results have been conflicting. This controversy may be caused by the effect of some confounders such as ethnicity and polytherapy. Moreover, expression of the ABCB1 gene is under the control of pregnane X receptor (PXR). Evidence showed that PXR gene contribute to the response to treatment. The aim of this study was to assess the association of ABCB1 and PXR genetic polymorphisms with response to the carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in epilepsy. Genotypes were assessed in 685 Chinese, Indian, and Malay epilepsy patients for ABCB1 (C1236T, G2677T, C3435T) and PXR (G7635A) polymorphisms. No association between these polymorphisms and their haplotypes, and interaction between them, with response to treatment was observed in the overall group or in the Chinese, Indian, and Malay subgroups. Our data showed that these polymorphisms may not contribute to the response to CBZ or VPA monotherapy treatment in epilepsy.

Association of HLA‐B*1502 allele with carbamazepine‐induced toxic epidermal necrolysis and Stevens–Johnson syndrome in the multi‐ethnic Malaysian population

Carbamazepine (CBZ), a frequently used anticonvulsant drug, is one of the most common causes of life-threatening cutaneous adverse drug reactions such as toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). Recent studies have revealed a strong association between HLA-B*1502 and CBZ-induced TEN/SJS in the Taiwan Han Chinese population. This study is aimed to investigate the association between human leucocyte antigens (HLA) and CBZ-induced TEN/SJS in the multi-ethnic Malaysian population. A sample of 21 unrelated patients with CBZ-induced TEN/SJS and 300 race-matched, healthy controls were genotyped for HLA-A, -B and -DR using polymerase chain reaction (PCR). Allele frequencies were compared. HLA-B*1502 was present in 75.0% (12/16) of Malay patients with CBZ-induced TEN/SJS but in only 15.7% (47/300) of normal controls (odds ratio 16.15, 95% confidence interval 4.57-62.4; corrected P-value = 7.87 × 10(-6) ), which suggests a strong association between HLA and CBZ-induced TEN/SJS. Additionally, HLA-B*1502 was found in all three Chinese and two Indian patients. Existing data show that frequencies of the HLA-B*1502 allele are generally much higher in Asian populations than in White European populations, which explains the higher incidences of SJS and TEN in Asian countries. HLA-B*1502 is strongly associated with CBZ-induced TEN/SJS in the Malay population in Malaysia, as has been seen in Han Chinese in Taiwan. This indicates that the genetic association apparent in the incidence of CBZ-induced TEN/SJS is linked with the presence of HLA-B*1502, irrespective of racial origin. Screening of patients for this genetic marker can help to prevent the occurrence of TEN/SJS.

Skeletal, dentoalveolar, and soft tissue cephalometric measurements of Malay transfusion-dependent thalassaemia patients

Thalassaemia is a public health problem in Malaysia. It is known to cause skeletal deformity. The purpose of this study was to compare the skeletal, dentoalveolar, and soft tissue features of Malay transfusion-dependent thalassaemia (TDT) patients with a Malay control group. Lateral cephalometric radiographs of 30 Malay (14 males and 16 females aged 6.4-21.8 years) TDT patients and 60 normal Malays matched for chronological age and gender were analysed and compared using an independent t-test. The TDT group showed a similar sagittal relationship to the control group but with a significantly increased (P < 0.01) mandibular plane inclination. They also showed a significantly shorter (P ≤ 0.001) mandibular body, ramus length, and posterior face height and consequently a smaller ratio of posterior to anterior face height (P < 0.01). The upper and lower lips were significantly procumbent (P < 0.001) in the TDT group together with a significantly smaller nasolabial angle (P < 0.05). Dentoalveolar measurements showed less proclined maxillary teeth in the TDT group compared with the controls (P < 0.05). The cephalometric features of Malay TDT patients were characterized by a mild Class II skeletal pattern, prominent vertical growth direction of the mandible, and protruded upper and lower lips.

No evidence for association between DRD3 and COMT with schizophrenia in a Malay population

Molecular components of the dopamine D3 receptor (DRD3) may play an important role in the pathophysiology of schizophrenia. Previous studies have demonstrated an association between DRD3 Ser9Gly and cathechol-o-methyltransferase (COMT, SNP = rs165656) polymorphisms and schizophrenia but the results were inconclusive. We investigated this apparent association between Ser9Gly (A/G) polymorphism and an intronic SNP (dbSNP or rs165656) in 261 Malay patients diagnosed with schizophrenia and 216 controls, using PCR-RFLP. The genotype distribution of the polymorphism DRD3 Ser9Gly was in Hardy-Weinberg equilibrium (HWE) for patients (P = 0.1251) and out of HWE for controls (P = 0.0137). However, both healthy controls and schizophrenia patients were out of HWE for the polymorphism COMT rs165656. Based on allele and genotype frequencies in both groups, we found no significant association of DRD3 Ser9Gly polymorphisms and COMT (rs165656) with schizophrenia in Malays. Further studies should examine the association between other dopamine-related genes and the behavioral phenotypes of schizophrenia.

Gene expression profiling in ethnic Malays with type 2 diabetes mellitus, with and without diabetic nephropathy

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD) among type 2 diabetes mellitus patients (DM) in Malaysia. This study used microarray analysis to determine the gene expression profiling in ethnic Malay patients with type 2 DM. A total of 312 patients were recruited; 25 were on dialysis due to ESRD, 128 were classified as normoalbuminuric, 93 as microalbuminuric and 66 as macroalbuminuric, based on urine albumin to creatinine ratio of <3.5, between 3.5 and 35 and =35 mg/mmol, respectively. Microalbuminuria was associated with up- and down-regulation of 2,694 and 2,538 genes, respectively, while macroalbuminuria was associated with up-regulation of 2,520 genes and down-regulation of 2,920 genes. There was significant up-regulation of 1,135 genes and down-regulation of 908 genes in the ESRD samples. Thirty-seven significantly up-regulated genes and 40 down-regulated genes were commonly expressed in all 3 groups of patients with worsening of renal functions. Up-regulated genes included major histocompatibility complex (HLA-C), complement component 3a receptor 1 (C3AR1), solute carrier family 16, member 3 (SLC16A3) and solute carrier family 9 (sodium/hydrogen exchanger) (SLC9A8). Consistently down-regulated genes included were bone morphogenetic phosphatase kinase (BMP2K), solute carrier family 12, member 1 (SLC12A1), solute carrier family 7 (SLC7A2), paternally expressed 10 (PEG10) and protein phosphatase 1 regulatory (inhibitor unit) (PPP1R1C). This study has identified several genes of interest, such as HLA-C, SLC16A3, SLC9A8, SLC12A1 and SLC7A2, that require verification of their roles as susceptibility genes for diabetic nephropathy in ethnic Malays with type 2 DM.

Abstract P3-13-03: Association between Ethnicity and Survival after Breast Cancer in a Multi-Ethnic Asian Setting: Results from the Singapore-Malaysia Hospital-Based Breast Cancer Registry

Abstract Background: Little is known on the impact of ethnicity on survival after breast cancer in the multi-ethnic Asian setting. Material and Methods: Using the multi-institutional Singapore-Malaysia hospital-based breast cancer registry, we investigated the association between ethnicity and risk of mortality after breast cancer in 3,366 patients diagnosed between 1990 and 2007 (Chinese: 77%, Malay: 15%, Indian: 8%). Kaplan-Meier analysis was used to estimate overall cumulative survival (OS). Multivariable hazard ratios (HR) adjusted for tumor and treatment characteristics were computed using Cox regression analysis after splitting follow-up time along the age-axis and calendar-time axis. Results: Malay patients presented at younger age compared to Chinese and Indians (47years vs 52years vs 53years, respectively, P&amp;lt;0.001) with larger tumors (35mm vs 24mm vs 30mm, respectively, P&amp;lt;0.001), and at later stages (TNM stage III or IV) (37% vs 23% vs 25%, respectively, P&amp;lt;0.001). Malay women were least likely to have undergone surgery, and most likely to receive chemotherapy. Five-year OS was 71.9% (95% CI: 69.7%-74.1%) in Chinese, 47.2% (95%CI: 41.9%-52.5%) in Malays and 62.7% (56.0%- 69.4%) in Indians. After adjustment for tumor and treatment characteristics, Malay patients had approximately 60% higher risk of death than the Chinese (HR:1.57; 95%CI:1.40-1.77). Indian ethnicity was not significantly associated with risk of mortality after breast cancer compared to Chinese (HR:1.12; 95%CI: 0.98-1.30). Conclusion: In the Asian setting, Malay ethnicity seems to be associated with significantly poorer survival after breast cancer, independent of tumor and treatment profile. The underlying reasons for this association are unclear but may be explained by variations in susceptibility to treatment, co-morbidity and lifestyle after diagnosis of breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-13-03.

Abstract P3-13-06: Racial Differences in Breast Cancer Biomarkers in the Three Ethnic Groups of Sarawak, Malaysia

Abstract Sarawak, Malaysia Introduction The Malaysian state of Sarawak has a mixed ethnic population of Natives, Chinese and Malays. Breast cancer (BC) is the most common cancer. We present preliminary results obtained on a case series of 1034 female BC patients diagnosed between 2001 and 2009, representative of the Sarawak patient population (as discussed in our previous publication: Devi et al. 2007). Methods Tumor markers were assessed using immuno-histochemistry, Her2 2+ and Her2 3+ were confirmed using FISH test. Patients were classified as follow: Luminal A : ER+ PR+ and Fish — Luminal B : ER+, PR+ and Fish + Her2-overexpressing : ER-, PR-and Fish — Triple-negative : ER-, PR-and Fish - Chi2 comparisons and multivariate logistic regressions were performed using SAS statistical software. The OR presented are adjusted on age and ethnic groups. Results BC incidence was higher among Chinese (ASR=30.6) than among Malay (ASR=21.2) or Natives (ASR=7.8). In our series, luminal B, Her2-overexpressing and triple negative subtypes were represented in respectively 12%, 11% and 29% of the patients. The triple negative subtype was more frequent among Natives cases (37%) or Malay cases (33%), significantly higher than among Chinese cases (23%). Compared to luminal A, triple negative patients were more likely to be Malay (OR = 2.07; 95%CI= [1.44-2.98]) or Natives (OR = 2.13; 95%CI= [1.48-3.04]), to have older age at menopause (OR for menopause &amp;gt;50 years = 1.59 ; 95%CI= [1.01-2.51]) and less likely to have familial history of BC (OR = 0.52; 95%CI= [0.3260.82]) or to have breast fed for 0 to 6 months (OR = 0.60 ; 95%CI= [0.37-0.97]). Malay and Native triple negative patients were more likely to be overweight when pre-menopausal (OR for BMI 25-29 vs. BMI&amp;lt;25 = 2.02; 95%CI=[1.02-3.97]), such a trend did not exist in Chinese patients. Compared to luminal A, Her2-overexpressing patients were more likely to be Malay (OR = 1.66; 95%CI= [1.01-2.70]) and to have children (OR parous vs nulliparous=1.99; 95%CI= [1.11-3.59]). The number of children did not influence the association. A borderline significant association (p=0.053) was observed with menopausal status Compared to luminal A, luminal B, were significantly more likely to be Malay (OR=2.10; 95%CI= [1.32-3.33]), to be premenopausal (OR=1.87; 95%CI=[1.13-3.10]) and to be over-weight (OR for BMI 25-29 vs. BMI&amp;lt;25 = 1.64; 95%CI=[1.06-2.53]) especially when premenopausal (OR=1.96; 95%CI= [1.05-3.65]). Surprisingly, age distribution did not differ between Luminal A, B, Her2- overexpressing and triple-negative patients, however 80% of our patients were &amp;lt;60. Conclusions The proportion of triple negative patients in our series revealed to be one of the highest ever reported, and was significantly higher than in Caucasian or other Asian cases series. Our results confirm the finding the HER2- overexpression is more frequent in Asians compared to whites or African American. Regarding risk factors our results did not conflict with those reported in the literature for Caucasian populations however some specific patterns were observed that need to be studied further. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-13-06.