East Asian Origin Research Articles

EGFR inhibitors: what have we learned from the treatment of lung cancer?

Tyrosine kinase inhibitors directed against the epidermal growth factor receptor (EGFR) are the first molecular-targeted agents to be approved in the US and other countries for the treatment of advanced non-small-cell lung cancer after failure of chemotherapy. Some patient characteristics, such as never-smoking, female gender, East Asian origin, adenocarcinoma histology, and bronchioloalveolar subtype, are associated with a greater benefit from treatment with EGFR inhibitors. Recently, studies have identified gene mutations targeting the kinase domain of the EGFR that are related to the response to inhibitors. Most EGFR mutations predict a higher benefit from treatment compared with wild-type receptors and are correlated with clinical features related to better outcome; some EGFR mutations, however, confer drug resistance. The analysis of material usually available from lung cancer patients, using techniques such as direct sequencing to determine EGFR mutational status, can be technically challenging. In this regard, high EGFR copy number and EGFR protein detected by immunohistochemistry can also be used to select those patients who would benefit from treatment. Prospective validation of biological and clinical markers of sensitivity needs to be performed.

GERD in British and south‐east Asian dyspeptic patients

Sirs, Mahadeva et al.’s1 paper on the correlation between British and south-east Asian patients and dyspepsia raises a number of fundamental issues. We are sceptical about the findings as we feel there are problems with the sampling and methodology in general. All hospital-based patient studies run the risk of not being representative of the population they are derived from. This bias is further exacerbated when patients from two different health systems and cultures as well as differing attitudes to health care are compared. We were surprised that only British Caucasian dyspeptics were recruited for the study whereas all Malaysians of a generic background were included and lumped together as south-east Asians (a term which also applies to the ethnically diverse inhabitants of Brunei, Burma, Cambodia, Indonesia, Laos, Singapore, Thailand and Vietnam). It would have been more appropriate for British dyspeptics, irrespective of race or at least of Asian origin, to have been included in the study, particularly as south Asian (Indian) descent has been shown to be a risk factor for gastro-oesophageal reflux disease (GERD) in a British community study.2 Moreover, both Britain and Malaysia have multiethnic and multicultural populations, some of whom are of east and south Asian origin. Hence, the inherent differences in the referral patterns and selection of patients between the two systems (which we are both acutely aware of having also worked in the UK) could alone account for the differences in findings between British and Malaysian patients. We feel that selective referencing has been used to convey the message that GERD is not common in the east. Relatively recent papers from Hong Kong and Malaysia (not mentioned in the article) revealed monthly reflux prevalence figures of 9.9% and 9.7% respectively.3, 4 Moreover, our endoscopy unit in a major teaching hospital reported a prevalence rate of 1.6% of histologically proven long segment Barrett's oesophagus and 4.6% short segment Barrett.5 These figures obtained from a study in which endoscopies were performed/supervised by a single consultant endoscopist (SR) between 1997 and 2000 contrast sharply with the 0.9% columnar-lined oesophagus diagnosed in south-east Asians by endoscopy personnel in various stages of training as reported by Mahadeva et al.’s1 group. This is especially so as there were a disproportionately high number of Indians (who have been shown to have the highest prevalence of Barrett's oesophagus in Malaysia5) in their study group (as was the case in SR's study), i.e. 31.2% when compared with the Federal Territory of Kuala Lumpur (research location) Indian population distribution of 10.6%.6 In our unit, trainees have great difficulty in diagnosing columnar-lined oesophagus endoscopically. Reasons include the belief that the accentuated or serrated squamo-columnar junctions are a normal variant and difficulty in identifying the gastro-oesophageal junction in complicated GERD.7 Almost a third of dyspeptic Malaysian patients in Mahadeva et al.’s1 study were on antisecretory therapy as opposed to none in their British counterparts. Surely this fact could account for at least partially, if not all, the observed differences in reflux symptoms and oesophagitis between Asian and Caucasian patients. In the study published from our endoscopy unit, all dyspeptic patients were off antisecretory therapy for a month prior to endoscopy.5 Not surprisingly, 77.7% of our patients with oesophagitis had reflux symptoms5 as opposed to 58.6% of Malaysian patients and 80.6% of British study subjects as reported by Mahadeva et al.’s1 group. Moreover, it is well known that there is no equivalent term for ‘heartburn’ (itself, a rather non-descript and inappropriate term for the retrosternal burning sensation arising from the epigastrium and moving up towards the neck) in the various languages and dialects spoken in Asia.7 In Malaysia, word descriptors such as ‘upwardly rising wind’, ‘acidic stomach’, ‘excessive burping’, ‘burning chest’ and ‘chest irritation’ are common expressions amongst Malay, Chinese and Indian patients to describe reflux symptoms,7 and these terms should be included in any locally validated questionnaire. Otherwise, low symptom reporting leads to reduced doctor referral for endoscopic examination. Moreover, there is data on ethnic differences in the perception of symptoms in other diseases as well.8 The authors have also stated that the western lifestyle is more sedentary than the east and may account for the apparent GERD differences; this, we believe, is pure speculation, as lifestyle was not one of the risk factors in their analysis, or was body mass index. Thus, for all the above reasons, we find it difficult to accept the authors’ conclusion that the perceived GERD variation between a monoethnic dyspeptic British patient population and a multiracial Malaysian dyspeptic cohort (who are not necessarily typical of other south-east Asians) is probably due to a combination of intrinsic ethnic differences and environmental influences. In short, weaknesses in study method could explain the differences and the findings should be interpreted cautiously.

Use of autosomal loci for clustering individuals and populations of East Asian origin

We studied the genetic relationships among East Asian populations based on allele frequency differences to clarify the relative similarities of East Asian populations with a specific focus on the relationships among the Koreans, the Japanese, and the Chinese populations known to be genetically similar. The goal is to find markers appropriate for differentiating among the specific populations. In this study, no prior data existed for Koreans and the markers were selected to differentiate Chinese and Japanese. We typed, using AB TaqMan assays, single-nucleotide polymorphisms (SNPs) at 43 highly selected mostly independent diallelic sites, on 386 individuals from eight East Asian populations (Han Chinese from San Francisco, Han Chinese from Taiwan, Hakka, Koreans, Japanese, Ami, Atayal, and Cambodians) and one Siberian population (Yakut). We inferred group membership of individuals using a model-based clustering method implemented by the STRUCTURE program and population clustering by using computer programs DISTANCE, NEIGHBOR, LSSEARCH, and DRAWTREE, respectively, calculating genetic distances among populations, calculating neighbor-joining and least-squares trees, and drawing the calculated trees. On average 52% of individuals in the three Chinese groups were assigned into one cluster, and, respectively, 78 and 69% of Koreans and Japanese into a different cluster. Koreans differentiated from the Chinese groups and clustered with the Japanese in the principal component analysis (PCA) and in the best least-squares tree. The majority of Koreans were difficult to distinguish from the Japanese. This study shows that a relatively few highly selected markers can, within limits, differentiate between closely related populations.

Aldehyde Dehydrogenase 2 Plays a Role in the Bioactivation of Nitroglycerin in Humans

Nitrates are used widely in clinical practice. However, the mechanism underlying the bioactivation of nitrates to release NO remains unclear. Recent animal data suggest that mitochondrial aldehyde dehydrogenase (ALDH2) plays a central role in nitrate bioactivation, but its role in humans is not known. We investigated the role of ALDH2 in the vascular effects of nitroglycerin (NTG) in humans in vivo. Forearm blood flow (FBF) responses to intra-arterial infusions of NTG, sodium nitroprusside (SNP), and verapamil were measured in 12 healthy volunteers before and after ALDH2 inhibition by disulfiram. All drugs caused a dose-dependent vasodilatation. However, only the response to NTG was significantly reduced after disulfiram therapy (33% reduction in area under the curve [AUC]; P=0.002). Separately, 11 subjects of East Asian origin, with the loss-of-function glu504lys mutation in the ALDH2 gene, received intra-arterial NTG, SNP, and verapamil. Only the FBF response to NTG was lower in the volunteers with the glu504lys mutation compared with East Asian and non-Asian wild-type control subjects (40% reduction in AUC; P=0.02). The findings suggest that ALDH2 is involved in the bioactivation of NTG in humans in vivo but accounts for less than half of the total bioactivation. This may be of clinical importance in patients with mutations in the ALDH2 gene and in those taking drugs that inhibit ALDH2.

EGFR mutations in lung cancers and sensitivity to gefitinib in Chinese

7089 Background: Radiographic regressions of tumors treated with gefitinib were observed in 28% of patients in Japan and 10% of those studied in Europe and the U.S. The characteristics of patient response to gefitinib were female, nonsmoker adenocarcinoma and East Asian origin. Recently, two groups have shown that EGFRmutations are associated with sensitivity of NSCLC to gefitinib. There are no any data about EGFR mutation in Chinese. Methods: Frozen tumor specimens from untreated patients with Stage I-IV NSCLC (n = 120) were obtained from Cancer Tissue Bank developed by our hospital. Paraffin-embedded materials were collected retrospectively for patients with NSCLC on gefitinib (n = 15). All 28 exons of EGFR were amplified in 5 specimens and exons 18, 19 and 21 were sought in other specimens. Results: Total 135 cases were enrolled onto the study. The patient characteristic was male: female = 94:31; Adenocarcinoma: other = 82:63; Smoker: nonsmoker =80:55. The mutations of EGFR were detected in 26 patients (25 cases with adeno, 1 with squamous). The EGFR mutation rate was 19.3%(26/135). Heterozygous substitution mutations were detected in exons 21 (11.9% of 16/135) and exons 18 (0.7%, 1/127). In-frame deletions detected in exons 19(8.9%, 12/128). Both substitution mutation and deletion mutation were detected in 3 patients not previously described. For adenocarcinoma subgroup the EGFR mutation rate was 30.5%(25/82). Male adenocarcinoma subgroup the EGFR mutation rate was 30.6%(15/49). Female adenocarcinoma subgroup the EGFR mutation rate was 30.3%(10/33). Smoking male adenocarcinoma the mutation was 53.3%(8/15). Nonsmoking male adenocarcinoma the mutation was 46.7%(7/15). 83.3% of 5/6 patients with positive mutation had clinically significant responses to the Gefitinib. Best response was seen in patients with exons 21 mutation (66.7% of 4/6). Conclusions: The in-frame deletions only occurred in exons 19 and most substitution mutation in exon 21. There was no significant difference of EGFR mutations between male and female, smoker and nonsmoker in Chinese. Lung adenocarcinoma with mutations EGFR are sensitive to Gefitinib. No significant financial relationships to disclose.

High Frequency of Gastric Colonization with MultipleHelicobacter pyloriStrains in Venezuelan Subjects

Multiple Helicobacter pylori strains may colonize an individual host. Using enzyme-linked immunosorbent assay and line probe assay (LiPA) techniques, we analyzed the prevalence of mixed H. pylori colonization in 127 subjects from Venezuela, a country of high H. pylori prevalence, from three regions representing different population groups: the Andes (Merida), where Caucasian mestizos predominate, a major city near the coast (Caracas), where Amerindian-Caucasian-African mestizos predominate, and an Amazonian community (Puerto Ayacucho), where Amerindians predominate and mestizos reflect Amerindian and Caucasian ancestry. Among 121 H. pylori-positive persons, the prevalence of cagA-positive strains varied from 50% (Merida) to 86% (Puerto Ayacucho) by LiPA. Rates of mixed colonization also varied, as assessed by LiPA of the vacA s (mean, 49%) and m (mean, 26%) regions. In total, 55% of the individuals had genotypic evidence of mixed colonization. vacA s1c, a marker of Amerindian (East Asian) origin, was present in all three populations, especially from Puerto Ayacucho (86%). These results demonstrate the high prevalence of mixed colonization and indicate that the H. pylori East Asian vacA genotype has survived in all three populations tested.

Discovery of an ancient lineage of Cyprinus carpio from Lake Biwa, central Japan, based on mtDNA sequence data, with reference to possible multiple origins of koi

MtDNA sequence data (c. 2100 bp of complete D‐loop + cytochrome b gene regions) showed a principal phylogenetic split within common carp Cyprinus carpio between the Lake Biwa wild form (n = 3) and ‘Eurasian’ wild (n = 18) and domesticated (n = 35) forms. This supports the idea of the ancient origin of the Lake Biwa wild form, as well as the East Asian origin of wild common carp, previously proposed on the basis of fossil data. In addition, a possible multiple origin of koi carp was indicated by the polyphyletic distribution of five mtDNA haplotypes of koi carp within the ‘Eurasian’ clade.

Genetic variation analysis of the Bali street dog using microsatellites

BackgroundApproximately 800,000 primarily feral dogs live on the small island of Bali. To analyze the genetic diversity in this population, forty samples were collected at random from dogs in the Denpasar, Bali region and tested using 31 polymorphic microsatellites. Australian dingoes and 28 American Kennel Club breeds were compared to the Bali Street Dog (BSD) for allelic diversity, heterozygosities, F-statistics, GST estimates, Nei's DA distance and phylogenetic relationships.ResultsThe BSD proved to be the most heterogeneous, exhibiting 239 of the 366 total alleles observed across all groups and breeds and had an observed heterozygosity of 0.692. Thirteen private alleles were observed in the BSD with an additional three alleles observed only in the BSD and the Australian dingo. The BSD was related most closely to the Chow Chow with a FST of 0.088 and also with high bootstrap support to the Australian dingo and Akita in the phylogenetic analysis.ConclusionsThis preliminary study into the diversity and relationship of the BSD to other domestic and feral dog populations shows the BSD to be highly heterogeneous and related to populations of East Asian origin. These results indicate that a viable and diverse population of dogs existed on the island of Bali prior to its geographic isolation approximately 12,000 years ago and has been little influenced by domesticated European dogs since that time.

The Freshwater Jellyfish (Craspedacusta Sowerbii) in Lithuanian Waters

The first record of the invasive freshwater jellyfish (Craspedacusta sowerbii) in Lithuanian waters is described. This hydromedusa of East Asian origin dispersed worldwide during the 1900s, mainly through unintentional introductions by humans. Although the exact way of invasion of C. sowerbii into Lithuanian waters remains unclear, the dispersal of freshwater jellyfish in temperate waters and the reported population explosion event might have been facilitated by recent climate change.

Restriction Polymorphism of Mitochondrial DNA in Koreans and Mongolians

Using the data on mitochondrial DNA (mtDNA) restriction polymorphism, the gene pools of Koreans (N = 164) and Mongolians (N = 48) were characterized. It was demonstrated that the gene pools were represented by the common set of mtDNA haplogroups of East Asian origin (M*, M7, M8a, M10, C, D4, G*, G2, A, B*, B5, F1, and N*). In addition to this set, mtDNA haplogroups D5 and Y were identified in Koreans while Mongolians possessed haplogroup Z. Only in Mongolians, a European component with the frequency of 10.4% and represented by the mtDNA types belonging to haplogroups K, U4, and N1, was identified. Phylogenetic and statistical analyses of the data on mtDNA variation in the populations of South Siberia, Central, and East Asia suggested the existence of interpopulation differentiation within these regions, the main role in which was played by the geographical and linguistic factors. Analysis of the pairwise F(ST) distances demonstrated close genetic similarity of Koreans to Northern Chinese, which in turn, were clearly different from Southern Chinese populations. Mongolians occupied an intermediate position between the ethnic groups of South Siberia and Central/East Asia.

How genetic is school myopia?

Myopia is of diverse aetiology. A small proportion of myopia is clearly familial, generally early in onset and of high level, with defined chromosomal localisations and in some cases, causal genetic mutations. However, in economically developed societies, most myopia appears during childhood, particularly during the school years. The chromosomal localisations characterised so far for high familial myopia do not seem to be relevant to school myopia. Family correlations in refractive error and axial length are consistent with a genetic contribution to variations in school myopia, but potentially confound shared genes and shared environments. High heritability values are obtained from twin studies, but rest on contestable assumptions, and require further critical analysis, particularly in view of the low heritability values obtained from parent-offspring correlations where there has been rapid environmental change between generations. Since heritability is a population-specific parameter, the values obtained on twins cannot be extrapolated to define the genetic contribution to variation in the general population. In addition, high heritability sets no limit to the potential for environmentally induced change. There is in fact strong evidence for rapid, environmentally induced change in the prevalence of myopia, associated with increased education and urbanisation. These environmental impacts have been found in all major branches of the human family, defined in modern molecular terms, with the exception of the Pacific Islanders, where the evidence is too limited to draw conclusions. The idea that populations of East Asian origin have an intrinsically higher prevalence of myopia is not supported by the very low prevalence reported for them in rural areas, and by the high prevalence of myopia reported for Indians in Singapore. A propensity to develop myopia in "myopigenic" environments thus appears to be a common human characteristic. Overall, while there may be a small genetic contribution to school myopia, detectable under conditions of low environmental variation, environmental change appears to be the major factor increasing the prevalence of myopia around the world. There is, moreover, little evidence to support the idea that individuals or populations differ in their susceptibility to environmental risk factors.

Studies of the neuromedin U-2 receptor gene in human obesity: evidence for the existence of two ancestral forms of the receptor

Central administration of neuromedin U (NMU) suppresses food intake acting through the NMU-2 receptor (NMU2R), which is expressed in the hypothalamus. We screened the NMU2R gene in 96 patients with severe early-onset obesity. A common variant haplotype was found (f-0.21). This common variant haplotype was unusual in nature, consisting of four non-contiguous missense changes in complete linkage disequilibrium, and across two separate exons. The variant haplotype resulted in four amino acid substitutions (S295T/F312L/P380L/ M385 V) and was present in several other Europid populations and in subjects of South Asian, East Asian and African American origin, but not in eleven African Pygmies. This variant haplotype was not associated with obesity or related traits in 500 subjects from a prospective population-based cohort. In summary, we have identified two markedly different isoforms of the NMU-2 receptor, presumably arising through an ancient and complex mutational event; no genetic associations between this haplotype and obesity-related traits were, however, discerned. Further investigation of the pharmacogenomic consequences of NMU2R variation in humans is warranted.

Sreening of pregnant women for hepatitis B markers in a French Provincial University Hospital (Limoges) during 15 years

During the 15 years from January 1984 to December 1998 the Limoges University Hospital screened 22,859 pregnant patients for hepatitis B surface antigen (HBs Ag) and identified 149 positives. The overall prevalence (0.65%) was intermediate between prevalences observed among women of French origin (0.29%), French West Indies islands (5.68%) and of foreign origin particulary South East Asian origin (7.14%) and Sub Saharan African origin (6.52%). Hepatitis B Virus (HBV) replication markers was detected with relative low frequence (HBe Ag: 14.4%; HBV-DNA: 13.7-20%) among HBs Ag positive mothers. Markers of delta hepatitis virus was found among 10.5% of the HBs Ag carrier pregnant women. During the 15 years study period variations of the global prevalence were not statistically significant. Universal prenatal screening and infant immunisation could greatly contribute to the control of HBV infection if the polemic about the hepatitis B vaccination recently propagated in France will not have a negative effect on the acceptance and national programme of vaccination.

Genetic evidence for an East Asian origin of domestic dogs.

The origin of the domestic dog from wolves has been established, but the number of founding events, as well as where and when these occurred, is not known. To address these questions, we examined the mitochondrial DNA (mtDNA) sequence variation among 654 domestic dogs representing all major dog populations worldwide. Although our data indicate several maternal origins from wolf, >95% of all sequences belonged to three phylogenetic groups universally represented at similar frequencies, suggesting a common origin from a single gene pool for all dog populations. A larger genetic variation in East Asia than in other regions and the pattern of phylogeographic variation suggest an East Asian origin for the domestic dog, approximately 15,000 years ago.

Neurilemmoma of the hard palate

Benign lesions originating in the oral cavity include minor salivary gland followed by nerve sheath tumors, as well as non-neoplastic lesions such as granular cell tumor, fibroepithelial polyps, and mucoceles.1 These must be differentiated from malignant neoplasms of epithelial, glandular, hematopoietic, and mesenchymal origin, as well as neural-based tumors such as malignant schwannoma. Notably, malignancies are relatively rare in the hard palate except in patients of East Asian origin, among whom the habit of reverse smoking greatly increases the incidence of primary squamous cell carcinoma.

High heritability of myopia does not preclude rapid changes in prevalence.

The aetiology of myopia is complex, but the major form of myopia results from an interplay between genetic factors and environmental influences. Although there are clear patterns of family inheritance and high heritability values in studies from all over the world,environmental factors are increasingly important in determining myopic outcomes in East Asia, and perhaps elsewhere. This is not paradoxical, as high heritability does not preclude strong environmental influences. The lower heritability values obtained from parent-offspring correlations in populations of East Asian origin where there are marked differences in the environmental exposures (education and urbanization) of parents and children, and where there has been a major shift in the population distribution of myopia, are consistent with this view. Despite the impact of environmental pressures in East Asia, there is evidence that parental myopia influences the position of their offspring within that new population distribution.

Phylogenetic origin of hepatitis B virus strains with precore C-1858 variant.

Mutations that prevent the expression of the hepatitis B e antigen frequently emerge in the immunoreactive phase of infection. The predominant mutation, the precore G-->A-1896 mutation, is restricted by the variability at position 1858 and is rare in strains with cytosine at nucleotide 1858. The C-1858 variant is characteristic of genotype A. It also occurs in genotypes C and F, but not in B, D, or E, explaining the geographical variation in the prevalence of precore mutants. C-1858 strains have been frequently observed in southeast Asia, but have not been phylogenetically characterized. By sequencing eight complete hepatitis B virus genomes, C-1858 variants of east Asian origin were found to constitute a phylogenetic entity within genotype C that probably diverged several hundred years ago. Further study of the distribution of this variant is warranted.

Neural tube defects in Victoria, Australia: potential contributing factors and public health implications

ObjectivesTo measure population prevalence and determine potential predictors of neural tube defects. MethodAnalysis of all births reported to a mandated collection of perinatal data, and terminations prior to 20 weeks' gestation that have been reported to a data collection of birth defects in Victoria from 1983 to 1997. Prevalence at birth and risk ratios of infant and maternal characteristics associated with neural tube defects were calculated. ResultsPrevalence of spina bifida has remained steady for 15 years and was 8.8/ 10,000 in 1997. Anencephaly increased to 7.9/10,000 in 1997. After exclusion of pregnancy terminations, the 1997 birth prevalence was 4.5/10,000 for spina bifida and 2.4/10,000 for anencephaly. Neural tube defects are identified in 1 in 1600 fetuses, the risk being significantly higher for epileptic women (Adjusted Odds Ratio (AOR)= 3.70, 95% Cl 2.25–6.07), multiple births (AOR=4.56, 95%Cl 3.46–6.02), teenage mothers (AOR=1.47, 95% Cl 1.09–2.00) compared with those aged 25–29, and women with three or more previous pregnancies (AOR=1.40, 95% Cl 1.10–1.78). The risk was lower for women of East Asian (AOR=0.70, 95% Cl 0.49–1.00) and Middle Eastern origin (AOR=0.60, 95% Cl 0.35–1.02) and these differences were approaching statistical significance. ConclusionTotal prevalence of neural tube defects did not decline up to 1997. ImplicationsIt is unlikely that targeting ‘at risk’ groups identified in this study would make a difference to neural tube defect incidence. However, consideration could be given to identifying larger ‘at risk’ groups such as those with homocysteine metabolism defects.

Genetic evidence of an early exit of Homo sapiens sapiens from Africa through eastern Africa.

The out-of-Africa scenario has hitherto provided little evidence for the precise route by which modern humans left Africa. Two major routes of dispersal have been hypothesized: one through North Africa into the Levant, documented by fossil remains, and one through Ethiopia along South Asia, for which little, if any, evidence exists. Mitochondrial DNA (mtDNA) can be used to trace maternal ancestry. The geographic distribution and variation of mtDNAs can be highly informative in defining potential range expansions and migration routes in the distant past. The mitochondrial haplogroup M, first regarded as an ancient marker of East-Asian origin, has been found at high frequency in India and Ethiopia, raising the question of its origin. (A haplogroup is a group of haplotypes that share some sequence variations.) Its variation and geographical distribution suggest that Asian haplogroup M separated from eastern-African haplogroup M more than 50,000 years ago. Two other variants (489C and 10873C) also support a single origin of haplogroup M in Africa. These findings, together with the virtual absence of haplogroup M in the Levant and its high frequency in the South-Arabian peninsula, render M the first genetic indicator for the hypothesized exit route from Africa through eastern Africa/western India. This was possibly the only successful early dispersal event of modern humans out of Africa.

The concept of facework: Its functions in the Hawaii model of mediation

AbstractFace facilitates cross‐cultural conflict resolution in Hawaii. A concept of east Asian origin, face is a subtle style of interpersonal encounter calculated to avoid personal embarrassment, or loss of poise, and to maintain an impression of self‐respect for others (Goffman, 1959). The majority of people living in Hawaii are from Asian cultures, such as Japanese, Chinese, and Korean. Not surprisingly, the face work concept is an important component in communication in Hawaii. The study begins by exploring facework historically, philosophically, and linguistically. Other factors are also discussed. In addition, I focus on the basic Hawaii model of mediation, examining the consequences of facework in the mediation process in the community. The perspective of cross‐cultural relevance and the flexibility of the method for conflict resolution are also discussed.