• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.6
• /
• pp.3443-3447
• /
• 2013

Aim: Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer associated death worldwide. The 5 year survival rate for esophageal cancer patients is very poor and accounts for only 12.3%. Besides environmental risk factors, genetic factors might play an important role in the esophageal cancer carcinogenesis. Methods: We conducted a hospital based case-control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): interleukin 9 (IL9) rs31563 C>T, IL9 rs31564 G>T, IL10 rs1800872 T>G, IL12A rs2243115 T>G, IL12B rs3212227 T>G and IL13 rs1800925 C>T on the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The genotypes were determined using a custom-by-design 48-Plex SNPscan$^{TM}$ Kit. Results: The IL10 rs1800872 T>G polymorphism was associated with an increased risk of ESCC. However, there were no significant links with the other five SNPs. Stratified analyses indicated no significant risk of ESCC associated with the IL10 rs1800872 T>G polymorphism evident among any subgroups. Conclusion: These findings indicated that functional polymorphism IL10 rs1800872 T>G might contribute to ESCC susceptibility. However, our results were obtained with a limited sample size, so that the power of our analysis was low. Future larger studies with more rigorous study designs of other ethnic populations are required to confirm the current findings.

• Genomics & Informatics
• /
• v.10 no.2
• /
• pp.110-116
• /
• 2012

Recent several studies have shown that the genetic variation of SCN5A is related with atrioventricular conduction block (AVB); no study has yet been published in Koreans. Therefore, to determine the AVB-associated genetic variation in Korean patients, we investigated the genetic variation of SCN5A in Korean patients with AVB and compared with normal control subjects. We enrolled 113 patients with AVB and 80 normal controls with no cardiac symptoms. DNA was isolated from the peripheral blood, and all exons (exon 2-exon 28) except the untranslated region and exon-intron boundaries of the SCN5A gene were amplified by multiplex PCR and directly sequenced using an ABI PRISM 3100 Genetic Analyzer. When a variation was discovered in genomic DNA from AVB patients, we confirmed whether the same variation existed in the control genomic DNA. In the present study, a total of 7 genetic variations were detected in 113 AVB patients. Of the 7 variations, 5 (G87A-A29A, intervening sequence 9-3C>A, A1673G-H558R, G3578A-R1193Q, and T5457C-D1819D) have been reported in previous studies, and 2 (C48G-F16L and G3048A-T1016T) were novel variations that have not been reported. The 2 newly discovered variations were not found in the 80 normal controls. In addition, G298S, G514C, P1008S, G1406R, and D1595N, identified in other ethnic populations, were not detected in this study. We found 2 novel genetic variations in the SCN5A gene in Korean patients with AVB. However, further functional study might be needed.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.6
• /
• pp.2597-2604
• /
• 2012

Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme involved in folate metabolism; a single nucleotide polymorphism (SNP) C677T has been reported to be linked with altered incidences of several diseases. We here conducted a meta-analysis of 15 published epidemiological studies with a total of 7306 cases and 8062 controls to evaluate its association with prostate cancer risk with overall and subgroup analyses. No statistical relationship was found overall with any genetic model (TT vs. CC: OR = 0.80, 95%CI = [0.62, 1.04], P = 0.094; CT vs. CC: OR = 0.97, 95%CI = [0.84; 1.12], P = 0.667; Dominant: OR = 0.94, 95%CI = [0.82; 1.07], P = 0.343; Recessive: OR = 0.81, 95%CI = [0.64; 1.04], P = 0.104), but after the exclusion of several studies, we could observe the homozygote TT to confer less susceptibility to prostate cancer in carriers; moreover, different effects of the polymorphism on prostate cancer risk was detected from subgroup analysis stratified by participants' residential region: significant reduced prostate cancer risk was found to be associated with the polymorphism from Asian studies (TT vs. CC: OR = 0.47, 95%CI = [0.33; 0.67], P < 0.001; CT vs. CC: OR = 0.73, 95%CI = [0.60; 0.90], P = 0.002; Dominant: OR = 0.67, 95%CI = [0.56; 0.82], P < 0.001; Recessive: OR = 0.55, 95%CI = [0.40; 0.76], P < 0.001) while studies from Europe indicated a slight increased risk under dominant model with marginal significance (OR = 1.14, 95%CI = [0.99; 1.30], P = 0.064). Moreover, the protective effect of the polymorphism against prostate cancer was also shown by studies performed in yellow Asians (TT vs. CC: OR = 0.48, 95%CI = [0.31; 0.75], P = 0.001; CT vs. CC: OR = 0.68, 95%CI = [0.51; 0.90], P = 0.006; Dominant: OR = 0.63, 95%CI = [0.48; 0.82], P < 0.001; Recessive: OR = 0.57, 95%CI = [0.39; 0.84], P = 0.004). We propose that these phenomena should be viewed with the consideration of folate metabolism profile and different gene background as well as living habits of different populations, and more relevant studies should be conducted to confirm our hypothesis and provide a comprehensive and clear picture concerning this topic.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.12
• /
• pp.6505-6510
• /
• 2012

Background: CYP2E1 encodes an enzyme which is mainly involved in bioactivation of potential carcinogens such as N-nitrosamines. Polymorphisms in the gene have been reported to be associated with cancer. The aim of this study was to evaluate genotype distributions and allele frequencies of five CYP2E1 polymorphisms in Iran Materials and Methods: Two hundred healthy individuals of an Iranian population from the southwest were included in this study. PCR-restriction fragment length polymorphism and Tetra-ARMS PCR methods were applied for CYP2E1 genotyping. Results: The allele frequencies for $^*5B$, $^*6$, $^*7B$, $^*2$, and $^*3$ were calculated to be 1.5%, 16%, 28.5%, 0%, and 2.75% respectively. Results of this study showed that no significant differences in genotype and allele frequencies of five single nucleotide polymorphisms with respect to the gender and tribes. The chi-square test showed that the genotype frequencies of $CYP2E1^*5B$ were similar to Caucasians, but the distribution of $CYP2E1^*6$ genotypes was similar to Asians. The frequencies of $CYP2E1^*2$ (0%) and $CYP2E1^*3$ (2.75%) alleles were within the range for Caucasians and Orientals. In the case of $CYP2E1^*7B$, the data werelimited. Accordingly, the results were only compared with Europeans and the comparison showed significant differences. Conclusions: In conclusion, ethnic and geographic differences may explain discrepancies in the prevalence of CYP2E1 polymorphisms.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.5
• /
• pp.1887-1893
• /
• 2012

The aim of this study was to detail characteristics of mammary Paget's disease (PD) representing the whole population in China. A total of 4211 female breast cancer inpatients at seven tertiary hospitals from seven representative geographical regions of China were collected randomly during 1999 to 2008. Data for demography, risk factors, diagnostic imaging test, physical examination and pathologic characters were surveyed and biomarker status was tested by immunohistochemistry. The differences of demography and risk factors between PD with breast cancer and other lesions were compared using Chi-square test or t-test, with attention to physical examination and pathological characters. The percentage of PD was 1.6% (68/4211) in all breast cancers. The mean age at diagnosis was 48.1, and 63.2% (43/68) patients were premenopausal. There is no difference in demography and risk factors between PD with breast cancer and other breast cancer (P > 0.05). The main pattern of PD in physical exam and pathologic pattern were patients presenting with a palpable mass in breast (65/68, 95.6%) and PD with underlying invasive cancer (82.4%, 56/68) respectively. The rate of multifocal disease was 7.4% (5/68). PD with invasive breast cancer showed larger tumor size, more multifocal disease, lower ER and PR expression and higher HER2 overexpression than those in other invasive breast cancer (P < 0.05). These results suggested that PD in China is a concomitant disease of breast cancer, and that PD with underlying invasive cancer has more multiple foci and more aggressive behavior compared with other breast invasive cancer. We address the urgent needs for establishing diagnostic and therapeutic guidelines for mammary PD in China.

• Journal of Genetic Medicine
• /
• v.4 no.1
• /
• pp.22-37
• /
• 2007

The autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases, clinically and genetically heterogeneous, characterized by degeneration of spinocerebellar pathways with variable involvement of other neural systems. At present, 27 distinct genetic forms of SCAs are known: SCA1-8, SCA10-21, SCA23, SCA25-28, DRPLA (dentatorubral-pallidoluysian atrophy), and 16q-liked ADCA (autosomal dominant cerebellar ataxia). Epidemiological data about the prevalence of SCAs are restricted to a few studies of isolated geographical regions, and most do not reflect the real occurrence of the disease. In general a prevalence of about 0.3-2 cases per 100,000 people is assumed. As SCA are highly heterogeneous, the prevalence of specific subtypes varies between different ethnic and continental populations. Most recent data suggest that SCA3 is the commonest subtype worldwide; SCA1, SCA2, SCA6, SCA7, and SCA8 have a prevalence of over 2%, and the remaining SCAs are thought to be rare (prevalence <1%). In this review, we highlight and discuss the SCA7. The hallmark of SCA7 is the association of hereditary ataxia and visual loss caused by pigmentary macular degeneration. Visual failure is progressive, bilateral and symmetrical, and leads irreversibly to blindness. This association represents a distinct disease entity classified as autosomal dominant cerebellar ataxia (ADCA) type II by Harding. The disease affectsprimarily the cerebellum and the retina by the moderate to severe neuronal loss and gliosis, but also many other central nervous system structures as the disease progresses. SCA7 is caused by expansion of an unstable trinucleotide CAG repeat in the ATXN7 gene encoding a polyglutamine (polyQ) tract in the corresponding protein, ataxin-7. Normal ATXN7 alleles contain 4-35 CAG repeats, whereas pathological alleles contain from 36->450 CAG repeats. Immunoblott analysis demonstrated that ataxin-7 is widely expressed but that expression levels vary among tissues. Instability of expanded repeats is more pronounced in SCA7 than in other SCA subtypes and can cause substantial lowering of age at onset in successive generations termed ‘anticipation’ so that children may become diseased even before their parents develop symptoms. The strong anticipation in SCA7 and the rarity of contractions should have led to its extinction within a few generations. There is no specific drug therapy for this neurodegenerative disorder. Currently, therapy remains purely symptomatic. Cellular models and SCA7 transgenic mice have been generated which constitute valuable resources for studying the disease mechanism. Understanding the pathogenetic mechanisms of neurodegeneration in SCAs should lead to the identification of potential therapeutic targets and ultimately facilitate drug discovery. Here we summarize the clinical, pathological, and genetic aspects of SCA7, and review the current understanding of the pathogenesis of this disorder. Further, we also review the potential therapeutic strategies that are currently being explored in polyglutamine diseases.

• Korean Journal of Biological Psychiatry
• /
• v.9 no.1
• /
• pp.25-33
• /
• 2002

Serotonin transporter(5-HTT) is one of the major action site of antidepressants in neuronal cells. According to the recent studies, it is known that the functional polymorphism in the promoter region of the 5-HTT gene(5-HTT linked polymorphism repetitive element in promoter region, 5-HTTLPR) is associated with antidepressant responsiveness, and the distributions of 5-HTTLPR is various among the different populations. Our preliminary study suggested that it is possible to measure the endophenotype of 5-HTTLPR genotype by examining the pharmacodynamic research of the 5-HTT in platelet membranes. However, there are limitations to predicting the antidepressant responsiveness only from the endophenotypic characteristics of 5-HTT gene promoter polymorphism, and therefore we propose to use the pharmacogenomic methods for overcoming these limitations. We found that the significant correlations existed among the genetic polymorphisms of biogenic amine transporters whose structure and characteristics are similar to the 5-HTT, and the predictable odds ratio of antidepressant responsiveness are increased significantly by combining the effect with other associated polymorphisms, compared to the effect of 5-HTT promoter polymorphism only. These results support the hypothesis that antidepressant treatment has to be individualized according to the genetic and ethnic background of depressed patients. It would be possible to develope the evaluation tools to predict the antidepressant responsiveness and its side effect profile, if scientists reveal the genes related to the action mechanism as well as the metabolism of antidepressants so as to discover the interaction of those genes and contribution of endogenotypes toward antidepressant responsiveness.

• Cross-Cultural Studies
• /
• v.48
• /
• pp.361-389
• /
• 2017

This essay examines 'precarity politics' by Judith Butler, a well-known gender theorist and queer philosopher, in Notes Towards a Performative Theory of Assembly (2015) focused on concepts as unchosen cohabitation of Hannah Arendt and unwilled proximity of Emmanuel Levinas. Butler's precarity politics is the condition of our dispossessed political beings with fundamental vulnerability and interdependency that cannot choose with whom we will live on this Earth. Butler's political ethics is twofold: on one hand, she examines significance of 'action'' the most significant vita activa in the public area, and 'plurality'' the condition-not only the necessary condition but the possible condition-for a political life suggested by Hannah Arendt in Human Condition; on the other hand, Butler reflects upon global precarity based on a diasporic precarious life in the social world towards freedom and equality. Unchosen cohabitation of plural humans on Earth, and global pervasion of precarity, that indicates "politically induced condition in which certain populations suffer from failing social and economic networks of support and become differentially exposed to injury, violence, and death," so called "differential distribution of precariousness," are practical possibilities of ethical and equal cohabitation of different ethnic groups in the social world. Ethical obligations or ethical demand to respond to others' suffering in distance and proximity originated from precarity politics, mentioned in Precarious Life, Parting Ways, and Frames of War, could be non-foundational joint of plural people living together globally. We should presume the 'reversibility' of distance and proximity in others' suffering, based on responsiveness and responsibility of others, if we want to stay attuned to the pain of others we never chose to live together. That is the significance of Butler's 'precarity politics' with 'ethical obligation' to accept 'unchosen plurality' of living population on Earth, and 'reversibility between of distance and proximity,' in her 'new plural and embodied body politics' or 'new corporeal ontology', through human primary vulnerability, fundamental interdependency, being exposed and responsive to suffering of others.