Risk Factor Analysis of Cutaneous Leishmaniasis in Sri Lanka through a Nationwide Survey.

Leishmaniasis in Sri Lanka was first reported in the early 1990s. Cutaneous leishmaniasis (CL) cases have markedly increased in recent years, demanding due attention from health authorities. The spatial distribution of CL is not homogeneous. This case-control study investigated factors that may contribute to this heterogeneous distribution through a nationwide study. Information on sociodemographic, economic, and environmental characteristics was collected from study participants (cases, n = 303; controls, n = 2,762). All individuals were followed up for 3 years, and signs of CL or associated complications were recorded. Differences in possible risk factors between cases and controls were analyzed. Individuals <18 years old, electricity supply, spending >2 hours outdoors, visiting jungles/water bodies, and living near CL patients were identified as risk factors. Household members of 1.3% of cases, 2.3% of controls residing within a perimeter of 500 m from a patient, and 0.8% of controls living beyond 2 km from a case developed CL. Thus, CL in Sri Lanka appears intertwined with living environment and host behavior. Common environmental factors may be responsible for the higher risk of CL in individuals living in close proximity to CL patients. This may at least partly explain the clustering of CL cases in selected areas of the country.

The use of recombinant K39, KMP11, and crude antigen-based indirect ELISA as a serological diagnostic tool and a measure of exposure for cutaneous leishmaniasis in Sri Lanka.

Cutaneous leishmaniasis (CL) in Sri Lanka is caused by Leishmania donovani, a parasite widely known to cause visceral leishmaniasis. Despite the fact that CL is not generally believed to elicit serological immune responses, recent studies show the presence of antibody responses against this atypical form of CL. This study assesses the potential of using recombinant K39 (rK39), KMP11, and crude parasite antigen-based indirect ELISAs as serological diagnostic tools and measures of exposure for CL in Sri Lanka. The study used serum samples from confirmed CL patients (n = 266) and apparently healthy individuals from endemic settings (n = 411). Serum samples from individuals residing in non-endemic areas were used as negative controls. In-house indirect ELISAs were optimized and validated for recombinant antigens. Previously validated crude parasite extract-based indirect ELISA was performed for comparison. The statistical analyses were performed using SPSS v26.0. The rK39 (sensitivity = 71.2%, specificity = 64%) and KMP11 (sensitivity = 79.2%, specificity = 71.4%) based indirect ELISA were shown to be less suitable for the diagnosis of CL, while crude parasite extract-based indirect ELISA (sensitivity = 82.4%, specificity = 85.7%) might be a better method of diagnosis. All 03 ELISAs seemed to be good methods as measures of exposure since correlations were observed between the seropositivity of all 03 ELISAs (rK39: p = 0.037, KMP11: p = 0.007, CrudeAg: p = 0.000) with provincial case incidences. The findings will be important in identifying the disease hotspots in order to design the control measures for CL induced by L. donovani in Sri Lanka.

Histological findings associated with treatment response in cutaneous leishmaniasis: a clinicopathological correlation study.

BACKGROUND: Treatment responses to cutaneous leishmaniasis (CL) observed in Sri Lanka show variability, ranging from quick healing to delayed or failed responses to routine medication. The determinants of these differences in treatment response are not well defined. This study aimed to identify predictive features of treatment response and outcome in localized CL caused by Leishmania donovani, focusing on both clinical and histopathological findings in the patients. METHODS: Tissue sections (n = 103) derived from 3 mm punch biopsies of parasitologically confirmed patients were assessed. Patients were followed up weekly until complete healing of skin lesions and were reviewed at the end of 6 months and 1 year. RESULTS: Healing required 7-21 weekly doses of intralesional sodium stibogluconate (IL-SSG) (mean = 12.2 ± 0.622). Twenty-nine (28.1%) patients were identified as delayed responders. None had recurred at the end of 1 year. The demographic or clinical features (age, gender, lesion type, size, location, and lesion duration) did not significantly influence the treatment response. A heavy parasite load and acanthosis were significant predictors of a delayed response to treatment (P < 0.001). Higher parasite loads were associated with inflammation of the entire dermis (P = 0.008), more intense infiltration of macrophages (p = 0.001), and epidermal atrophy (P = 0.033). Well-formed granulomas were inversely proportional to parasite loads. CONCLUSIONS: Histology findings proved to be better prognostic markers than clinical features for delayed responders to treatment and will aid in targeted patient management when tissue biopsies are performed in the initial diagnosis of CL.

Diagnostic Tools for Cutaneous Leishmaniasis Caused by Leishmania donovani: A Narrative Review.

Leishmaniasis, a neglected tropical disease, encompasses a spectrum of clinical conditions and poses a significant risk of infection to over one billion people worldwide. Visceral leishmaniasis (VL) in the Indian sub-continent (ISC), where the causative parasite is Leishmania donovani, is targeted for elimination by 2025, with some countries already reaching such targets. Other clinical phenotypes due to the same species could act as a reservoir of parasites and thus pose a challenge to successful control and elimination. Sri Lanka has consistently reported cutaneous leishmaniasis (CL) due to L. donovani as the primary disease presentation over several decades. Similar findings of atypical phenotypes of L. donovani have also been reported from several other countries/regions in the Old World. In this review, we discuss the applicability of different methods in diagnosing CL due to L. donovani and a comprehensive assessment of diagnostic methods spanning clinical, microscopic, molecular, and immunological approaches. By incorporating evidence from Sri Lanka and other regions on L. donovani-related CL, we thoroughly evaluate the accuracy, feasibility, and relevance of these diagnostic tools. We also discuss the challenges and complexities linked to diagnosing CL and review novel approaches and their applicability for detecting CL.

Associations of meditation with telomere dynamics: a case-control study in healthy adults.

Introduction: Telomeres are protective end caps of chromosomes which naturally shorten with each cell division and thus with age. Short telomeres have been associated with many age-related diseases. Meditation has come to the fore as a mind-body practice which could influence the telomere dynamics underlying these phenomena. We previously reported meditation to be associated with higher telomerase levels, mindfulness and quality of life. Here, reporting on the same study population, we describe associations between long-term meditation and telomere length (TL), expression of hTERT and hTR genes and methylation of the promoter region of hTERT gene. Methods: Thirty healthy meditators and matched non-meditators were recruited. TL was measured using quantitative PCR, gene expression was assessed using reverse transcriptase PCR, and methylation level was quantified by bisulfite-specific PCR followed by Sanger sequencing. Comparisons between meditators and controls were carried out using t-tests, while Pearson correlation was used to identify correlations, and regression was used to identify predictors. Results: Males comprised 63.4% of each group with an average age of 43 years. On average, they had meditated daily for 5.82 h (±3.45) for 6.8 years (±3.27). Meditators had longer relative TLs (p = 0.020), and TL decreased with age (p < 0.001) but was not associated with other socio-demographic variables. Regression analysis showed that age (p < 0.001) and duration of meditation (p = 0.003) significantly predicted TL. The meditators showed higher relative expression of hTERT (p = 0.020) and hTR (p = 0.029) genes while the methylation level of the promoter region of hTERT gene was significantly lower when compared to non-meditators (p < 0.001). Negative correlations were identified between the methylation level of the promoter region of hTERT gene and the expression of the hTERT gene (p = 0.001) and duration of meditation (p = 0.001). Conclusion: The findings suggest that meditation as a lifestyle practice has multi-level beneficial effects on telomere dynamics with potential to promote healthy aging.

First evidence of experimental genetic hybridization between cutaneous and visceral strains of Leishmania donovani within its natural vector Phlebotomus argentipes.

Leishmaniasis is a neglected tropical disease caused by protozoan parasites of genus Leishmania, and transmitted by different species of Phlebotomine sand flies. More than 20 species of Leishmania are known to cause disease in humans and other animals. Leishmania donovani species complex is known to have a vast diversity of clinical manifestations in humans, but underlying mechanisms for such diversity are yet unknown. Long believed to be strictly asexual, Leishmania have been shown to undergo a cryptic sexual cycle inside its sandfly vector. Natural populations of hybrid parasites have been associated with the rise of atypical clinical outcomes in the Indian subcontinent (ISC). However, formal demonstration of genetic crossing in the major endemic sandfly species in the ISC remain unexplored. Here, we investigated the ability of two distinct variants of L. donovani associated with strikingly different forms of the disease to undergo genetic exchange inside its natural vector, Phlebotomus argentipes. Clinical isolates of L. donovani either from a Sri Lankan cutaneous leishmaniasis (CL) patient or an Indian visceral leishmaniasis (VL) patient were genetically engineered to express different fluorescent proteins and drug-resistance markers and subsequently used as parental strains in experimental sandfly co-infection. After 8 days of infection, sand flies were dissected and midgut promastigotes were transferred into double drug-selective media. Two double drug-resistant, dual fluorescent hybrid cell lines were recovered, which after cloning and whole genome sequencing, were shown to be full genomic hybrids. This study provides the first evidence of L. donovani hybridization within its natural vector Ph. argentipes.

Cytokine and phenotypic cell profiles in human cutaneous leishmaniasis caused by Leishmania donovani.

BACKGROUND: The innate immune mediators are likely to influence the clinical phenotype of leishmaniasis by primary responses which limit or facilitate the spread of the parasite, as well as by modulating adaptive immunity. This study investigated the response of key innate immune cells in a focus which regularly reports localised cutaneous leishmaniasis (LCL) caused by Leishmania donovani, a species which typically causes visceral disease. METHODS: Peripheral blood mononuclear cell (PBMC) derived macrophages and dendritic cells from patients with LCL and healthy controls from endemic and non-endemic areas, were stimulated with soluble Leishmania antigen (SLA). Inflammatory mediators produced by macrophages (TNF-α/TGF-ß/IL-10, ELISA; NO, Griess method) and dendritic cells (IL-12p70, IL-10, flowcytometry) and macrophage expression of surface markers of polarization, activation and maturation (flowcytometry) were determined at 24h, 48h and 72h and compared. Study was conducted prospectively from 2015-2019. RESULTS: Patient derived macrophages and dendritic cells produced higher levels of both pro and anti-inflammatory mediators compared to controls (p<0.05) with the best discrimination for active disease observed at 72h. Data demonstrated an early activation of macrophages and a subsequent pro-inflammatory bias, as indicated by temporal profiles of TNF-α/TGF-ß and TNF-α/IL-10 ratios and higher proportions of classical (M1) macrophages. Higher TGF-ß levels were observed in cells from patients with ulcerated or persistent lesions. Immune responses by cells derived from controls in endemic and non-endemic regions did not differ significantly from each other. CONCLUSIONS: The overall immunophenotypic profile suggests that LCL observed in the country is the result of a balancing immune response between pro-inflammatory and regulatory mediators. The mediators which showed distinct profiles in patients warrant further investigation as potential candidates for immunotherapeutic approaches. A comparison with visceral leishmaniasis caused by the same species, would provide further evidence on the differential role of these mediators in the resulting clinical phenotype.

Assessment of knowledge and perceptions on leishmaniasis: An island-wide study in Sri Lanka.

Cutaneous leishmaniasis (CL) is a notifiable disease in Sri Lanka with increasing case numbers reported from every part of the country. In addition to disease treatment and vector control measures, knowledge and perceptions in a community are key contributors to a successful intervention program. An island-wide survey was carried out to assess the knowledge and perceptions regarding CL across the island, with 252 confirmed CL cases and 2,608 controls. Data was collected by trained personnel, using a pre-tested Case Reporting Form (CRF). Although the percentage who referred to CL by its correct name was low (1.4%), majority stated that it is a fly induced skin disease (79.1%). Knowledge on the symptoms, curability and the name of the vector was high in these communities, but specific knowledge on vector breeding places, biting times and preventive methods were poor. The patients were more knowledgeable when compared to the controls. Differences in the level of knowledge could be identified according to the level of education of the participants as well as across the different areas of the country. The main source of information was through the healthcare system, but the involvement of media in educating the communities on the disease was minimal. While this study population was unaccustomed to the use of repellants or sprays, the use of bed nets was high (77.7% of the participants) in this study population. Although misconceptions and incorrect practices are rare in Sri Lankan communities, promoting health education programs which may improve disease awareness and knowledge on vector and its control will further strengthen the control and prevention strategies.

Impact of Meditation-Based Lifestyle Practices on Mindfulness, Wellbeing, and Plasma Telomerase Levels: A Case-Control Study.

Meditation involves psychophysical training which can result in a range of benefits including creating a calm mind and increasing self-awareness, relaxation, and tranquility. Increasing evidence, mostly based on short-term focused interventions, suggests that meditation-based activities may also have favorable effects on physical wellbeing including cellular aging. Hence, the aim of this study was to investigate if continued practice of meditation benefited quality of life, state of mindfulness, and plasma telomerase level in healthy adults. 30 long-term and skilled meditators were recruited from meditation centers in different parts of the island following a two-tier screening process of 70 eligible participants and 30 age- and gender-matched healthy non-meditators were recruited from the community. Mindfulness level and the quality of life were measured using the Five Facet Mindfulness Questionnaire (FFMQ) and Quality of Life Questionnaire, respectively, while the levels of plasma telomerase enzyme were measured using Enzyme-Linked Immunosorbent Assay. Skilled meditators had a better mindfulness level (p < 0.001) and quality of life (QOL; p < 0.001) than those in the comparison group. Similarly, higher plasma telomerase levels were observed in skilled meditators compared to non-meditators (p = 0.002). Trait mindfulness level and plasma telomerase level showed a significant relationship with the duration of meditation practice (p = 0.046 and p = 0.011, respectively). Regression analysis indicated that trait mindfulness level (p < 0.001) significantly predicts the plasma telomerase level. The findings of this comparative study add to the evidence on sustained benefits of meditation on wellbeing and healthy aging and supports incorporating meditation-based activities into lifestyle practices.

The effects of meditation on length of telomeres in healthy individuals: a systematic review.

BACKGROUND: Meditation-based practices have been suggested to result in many biological benefits which include reduction of attrition of telomeres, the protective nucleotide-protein complexes at termini of eukaryotic chromosomes. This systematic review evaluated the effects of meditation on telomere length (TL) in healthy adults. METHODS: Randomized controlled trials (RCTs) and observational studies conducted to determine the effects of meditation on TL in healthy individuals, published up to July 2020 were retrieved by searching seven electronic databases (PubMed, Scopus, PsycINFO, EMBASE, Cochrane Library, CINAHL and Google Scholar). The methodological quality of RCTs and observational studies was assessed using the Cochrane Collaboration Risk of Bias Tool and Joanna Briggs Institute critical appraisal checklist, respectively. The data was synthesized narratively and the effect estimates of TL in the RCTs were synthesized using alternative methods as a meta-analysis was not conducted. The certainty of evidence was classified according to the GRADE system. RESULTS: A total of 1740 articles were screened. Five studies comprising two RCTs and three case-control studies (CCS) were included in the final review based on the inclusion and exclusion criteria. The combined sample consisted of 615 participants with 41.7% males. Average age of participants was 47.7 years. One CCS and one RCT reported significant beneficial effects of meditation on TL while the two remaining CCS and the RCT showed positive effects of meditation on TL which were not significant. For all CCS and one RCT, the methodological quality was high while the remaining RCT was of moderate quality. The quality of evidence for the primary outcome was moderate in RCTs. CONCLUSION: The effect of meditation on TL per se is still unclear. Strictly designed and well-reported RCTs with larger sample sizes are required to provide evidence of higher quality. SYSTEMATIC REVIEW REGISTRATION: The protocol of this review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database (registration number: CRD42020153977 ).

Spatiotemporal distribution of cutaneous leishmaniasis in Sri Lanka and future case burden estimates.

BACKGROUND: Leishmaniasis is a neglected tropical vector-borne disease, which is on the rise in Sri Lanka. Spatiotemporal and risk factor analyses are useful for understanding transmission dynamics, spatial clustering and predicting future disease distribution and trends to facilitate effective infection control. METHODS: The nationwide clinically confirmed cutaneous leishmaniasis and climatic data were collected from 2001 to 2019. Hierarchical clustering and spatiotemporal cross-correlation analysis were used to measure the region-wide and local (between neighboring districts) synchrony of transmission. A mixed spatiotemporal regression-autoregression model was built to study the effects of climatic, neighboring-district dispersal, and infection carryover variables on leishmaniasis dynamics and spatial distribution. Same model without climatic variables was used to predict the future distribution and trends of leishmaniasis cases in Sri Lanka. RESULTS: A total of 19,361 clinically confirmed leishmaniasis cases have been reported in Sri Lanka from 2001-2019. There were three phases identified: low-transmission phase (2001-2010), parasite population buildup phase (2011-2017), and outbreak phase (2018-2019). Spatially, the districts were divided into three groups based on similarity in temporal dynamics. The global mean correlation among district incidence dynamics was 0.30 (95% CI 0.25-0.35), and the localized mean correlation between neighboring districts was 0.58 (95% CI 0.42-0.73). Risk analysis for the seven districts with the highest incidence rates indicated that precipitation, neighboring-district effect, and infection carryover effect exhibited significant correlation with district-level incidence dynamics. Model-predicted incidence dynamics and case distribution matched well with observed results, except for the outbreak in 2018. The model-predicted 2020 case number is about 5,400 cases, with intensified transmission and expansion of high-transmission area. The predicted case number will be 9115 in 2022 and 19212 in 2025. CONCLUSIONS: The drastic upsurge in leishmaniasis cases in Sri Lanka in the last few year was unprecedented and it was strongly linked to precipitation, high burden of localized infections and inter-district dispersal. Targeted interventions are urgently needed to arrest an uncontrollable disease spread.

Spatial Epidemiologic Trends and Hotspots of Leishmaniasis, Sri Lanka, 2001-2018.

Leishmaniasis, a neglected tropical disease, is on the decline in South Asia. However, cases of cutaneous leishmaniasis have risen in Sri Lanka since 2001, and the lack of in-depth research on its epidemiologic characteristics hampers control efforts. We analyzed data collected from patients with cutaneous leishmaniasis in Sri Lanka during 2001-2018 to study temporal and geographic trends and identify and monitor disease hotspots. We noted a progression in case rates, including a sharp rise in 2018, showing temporal expansion of disease-prevalent areas and 2 persistent hotspots. The northern hotspot shifted and shrank over time, but the southern hotspot progressively expanded and remained spatially static. In addition, we noted regional incidence differences for age and sex. We provide evidence of temporally progressive and spatially expanding incidence of leishmaniasis in Sri Lanka with distinct geographic patterns and disease hotspots, signaling an urgent need for effective disease control interventions.

Electrophoretic mobility shift assays implicate XRCC2:rs3218550C>T as a potential low-penetrant susceptibility allele for sporadic breast cancer.

OBJECTIVE: A previous study undertaken at our centre to identify common genetic variants associated with sporadic breast cancer in Sri Lankan women showed that the T allele of rs3218550, located in the 3'untranslated region of X-ray repair cross-complementing gene-2 (XRCC2), increased breast cancer risk by 1.5-fold. Dual luciferase reporter assays performed in MCF-7 breast cancer cells showed a putative transcriptional repressor effect exerted mainly by the T allele. Electrophoretic mobility shift assays were conducted to further investigate the interaction of this variant with DNA-binding protein, using nuclear protein extracts derived from MCF-7 cells. RESULTS: An allele-specific differential binding was observed. The T allele resulted in differential DNA-protein complex binding as evidenced by the presence of multiple bands of increased intensity compared to the wild-type C allele. This implies possible alteration in binding of regulatory proteins by the variant allele. These results implicate XRCC2:rs3218550C>T as a potential low-penetrant susceptibility allele for sporadic breast cancer. XRCC2 is known to play an essential role in homologous recombination repair of DNA double-strand breaks. It is plausible that this variant may be exerting regulatory effects on XRCC2 gene expression leading to altered DNA repair capacity. Further functional studies are warranted to validate this finding.

Genotype data for single nucleotide polymorphism markers in sporadic breast cancer related genes in a Sri Lankan case-control cohort of postmenopausal women.

OBJECTIVE: The data presented herein represents the raw genotype data of a recently conducted larger study which investigated the association of single nucleotide polymorphisms (SNPs) in breast cancer related genes with the risk and clinicopathological profiles of sporadic breast cancer among Sri Lankan women. A case-control study design was adopted to conduct SNP marker disease association testing in an existing blood resource obtained from a cohort of Sri Lankan postmenopausal women with clinically phenotyped sporadic breast cancer and healthy postmenopausal women. The list of haplotype-tagging SNP markers for genotyping was selected based on information available in the published literature and use of bioinformatics tools and databases. Genotyping of 57 selected SNPs in 36 breast cancer related genes was performed using the iPLEX Sequenom Mass-Array platform. DATA DESCRIPTION: The raw genotype data for the 57 SNPs genotyped in 350 women with breast cancer and 350 healthy women are presented in this article. This data might be relevant to other researchers involved in investigating the role of SNPs in breast cancer related genes with the risk of sporadic breast cancer in South Asian populations.

Health in rural Sri Lanka: A cross-sectional survey of three rural districts

Introduction: Sri Lanka has a predominantly rural population. However, there is a dearth of research on health and socioeconomic issues in this group. Objective: To describe basic socioeconomic characteristics and health profile in a rural population. Methods: A descriptive cross-sectional household survey was conducted in 1950 households in three rural districts, selected by a three-stage stratified cluster sampling method. Results: The population pyramid showed an ageing population (dependency ratio of 50%). Only 39% had completed GCE (ordinary level). Unemployment rates were high (25% males, 76% females). Agriculture and related work were main occupations. Most lacked amenities (e.g. 61% households lacked a refrigerator) and practiced inappropriate methods of waste disposal (e.g. open burning by 72%). Household illnesses were frequent: episodes of acute illness within two weeks, injuries within past year and chronic illness were reported from 35.9%, 14.9% and 48.3% households. The prevalence of chronic diseases in adults >20 years were high: diabetes 13.5%, hypertension 16.7% and overweight/obesity 28.2%. Of the males, 22.1% smoked and 12.3% took alcohol. Almost 25% adults chewed betel. Reports of snake bite, dog bites and suicide/attempted suicide were seen in 15.5%, 9.7% and 3.0% households respectively. Conclusions: This study shows a unique clustering of health-related problems in rural Sri Lanka. This was characterized by demographic transition, burden from snake bites, chronic diseases and acute illnesses. There were resource limitations and low levels of education. Cohort studies and comparisons with urban areas will enable further elucidation of determinants of health and other issues in rural Sri Lanka.

Genomic insights into virulence mechanisms of Leishmania donovani: evidence from an atypical strain.

BACKGROUND: Leishmaniasis is a neglected tropical disease with diverse clinical phenotypes, determined by parasite, host and vector interactions. Despite the advances in molecular biology and the availability of more Leishmania genome references in recent years, the association between parasite species and distinct clinical phenotypes remains poorly understood. We present a genomic comparison of an atypical variant of Leishmania donovani from a South Asian focus, where it mostly causes cutaneous form of leishmaniasis. RESULTS: Clinical isolates from six cutaneous leishmaniasis patients (CL-SL); 2 of whom were poor responders to antimony (CL-PR), and two visceral leishmaniasis patients (VL-SL) were sequenced on an Illumina MiSeq platform. Chromosome aneuploidy was observed in both groups but was more frequent in CL-SL. 248 genes differed by 2 fold or more in copy number among the two groups. Genes involved in amino acid use (LdBPK_271940) and energy metabolism (LdBPK_271950), predominated the VL-SL group with the same distribution pattern reflected in gene tandem arrays. Genes encoding amastins were present in higher copy numbers in VL-SL and CL-PR as well as being among predicted pseudogenes in CL-SL. Both chromosome and SNP profiles showed CL-SL and VL-SL to form two distinct groups. While expected heterozygosity was much higher in VL-SL, SNP allele frequency patterns did not suggest potential recent recombination breakpoints. The SNP/indel profile obtained using the more recently generated PacBio sequence did not vary markedly from that based on the standard LdBPK282A1 reference. Several genes previously associated with resistance to antimonials were observed in higher copy numbers in the analysis of CL-PR. H-locus amplification was seen in one cutaneous isolate which however did not belong to the CL-PR group. CONCLUSIONS: The data presented suggests that intra species variations at chromosome and gene level are more likely to influence differences in tropism as well as response to treatment, and contributes to greater understanding of parasite molecular mechanisms underpinning these differences. These findings should be substantiated with a larger sample number and expression/functional studies.

What information and the extent of information research participants need in informed consent forms: a multi-country survey.

BACKGROUND: The use of lengthy, detailed, and complex informed consent forms (ICFs) is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in biomedical research. METHODS: This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 (not important) to 5 (very important). RESULTS: Of the 2484 questionnaires distributed, 2113 (85.1%) were returned. The majority of respondents considered most elements required in the ICF to be 'moderately important' to 'very important' for their decision making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45, respectively). CONCLUSIONS: Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF.

Relative normalized luciferase activity for the recombinant vector constructs carrying the ancestral and variant alleles for XRCC2:rs3218550 and PHB:rs6917.

OBJECTIVE: The data presented herein represents the preliminary results of the functional assays of a recently conducted larger study in which two single nucleotide polymorphisms (SNPs) [XRCC2:rs3218550 and PHB:rs6917] were significantly associated with risk of breast cancer among Sri Lankan postmenopausal women. The rs3218550 T allele and rs6917 A allele were found to increase breast cancer risk by 1.5-fold and 1.4-fold, respectively. Both SNPs are located in the 3'untranslated region (3'UTR) of the respective genes. It was hypothesized that these non-coding SNPs may be exerting some transcriptional regulatory effects on gene expression. Their putative functional effects were further investigated by generating bioluminescent recombinant experimental reporter gene constructs carrying the ancestral and variant alleles of these 2 SNPs, transiently transfecting them in MCF-7 breast cancer cell lines and performing dual-luciferase reporter gene assays to measure the luminescent signals. DATA DESCRIPTION: The normalized relative luciferase activity for the recombinant vector constructs carrying the ancestral and variant alleles for XRCC2:rs3218550 and PHB:rs6917 are presented herein. This data might be of relevance to other researchers involved in delineating the functional mechanisms of SNPs located in the 3'UTR of the XRCC2 and PHB breast cancer related genes.

Genetic Variants Associated with Clinicopathological Profiles in Sporadic Breast Cancer in Sri Lankan Women.

PURPOSE: Several single nucleotide polymorphisms (SNPs) have been reported to be associated with clinicopathological profiles in sporadic breast cancer based on studies conducted on major population groups. The knowledge of the effects of these common genetic variants in South Asian populations remains limited. The present study aimed to investigate the association between a selected set of SNPs and the clinicopathological profiles in sporadic breast cancer in Sri Lankan women. METHODS: A total of 350 postmenopausal women with histologically confirmed invasive breast cancer were genotyped for 58 SNPs located in 36 breast cancer related genes. The clinicopathological factors that were investigated included age of onset, tumor histologic grade, and lymph node involvement, as well as estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status. Association testing was performed using logistic regression models adjusted for confounding factors. RESULTS: Seven SNPs showed significant associations with clinicopathological profiles in breast cancer. The G allele of BRCA1:rs799917 (p=0.047; ß [standard error; SE]=-1.069 [0.537]) and the G allele of NQO2:rs17136117 (p=0.040, ß [SE]=1.901 [0.923]) were found to be associated with age of onset between 50 and 59 years. The C allele of CDH1:rs13689 (odds ratio [OR], 2.121; p=0.033) was found to be associated with ER-positive breast cancer. The A allele of AKT1:rs1130214 (OR, 2.095; p=0.011) and the C allele of NQO2:rs2071002 (OR, 1.632; p=0.045) were associated with HER2-positive breast cancer. The C allele of BRCA2:rs15869 (OR, 1.600; p=0.041) and the C allele of CCND1:rs7177 (OR, 1.555; p=0.041) were associated with high tumor histologic grade. CONCLUSION: The common genetic variants identified in the AKT1, BRCA1, BRCA2, CCND1, CDH1, and NQO2 genes could serve as potential clinical and prognostic biomarkers in sporadic breast cancer patients. Further studies are required to validate our current findings in other populations.

Genetic determinants of sporadic breast cancer in Sri Lankan women.

BACKGROUND: While a range of common genetic variants have been identified to be associated with risk of sporadic breast cancer in several Western studies, little is known about their role in South Asian populations. Our objective was to examine the association between common genetic variants in breast cancer related genes and risk of breast cancer in a cohort of Sri Lankan women. METHODS: A case-control study of 350 postmenopausal women with breast cancer and 350 healthy postmenopausal women was conducted. Genotyping using the iPLEX GOLD assay was done for 56 haplotype-tagging single nucleotide polymorphisms (SNPs) in 36 breast cancer related genes. Testing for association was done using an additive genetic model. Odds ratios and 95% confidence intervals were calculated using adjusted logistic regression models. RESULTS: Four SNPs [rs3218550 (XRCC2), rs6917 (PHB), rs1801516 (ATM), and rs13689 (CDH1)] were significantly associated with risk of breast cancer. The rs3218550 T allele and rs6917 A allele increased breast cancer risk by 1.5-fold and 1.4-fold, respectively. The CTC haplotype defined by the SNPs rs3218552|rs3218550|rs3218536 on chromosome 7 (P = 0.0088) and the CA haplotype defined by the SNPs rs1049620|rs6917 on chromosome 17 (P = 0.0067) were significantly associated with increased risk of breast cancer. The rs1801516 A allele and the rs13689 C allele decreased breast cancer risk by 0.6-fold and 0.7-fold, respectively. CONCLUSIONS: These findings suggest that common genetic polymorphisms in the XRCC2, PHB, CDH1 and ATM genes are associated with risk of breast cancer among Sri Lankan postmenopausal women. The exact biological mechanisms of how these variants regulate overall breast cancer risk need further evaluation using functional studies.