• Title/Summary/Keyword: Cohort Analysis

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Prognostic Significance of TP53 Mutations and Single Nucleotide Polymorphisms in Acute Myeloid Leukemia: A case Series and Literature Review

  • Zeichner, Simon Blechman;Alghamdi, Sarah;Elhammady, Gina;Poppiti, Robert John;Castellano-Sanchez, Amilcar
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1603-1609
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    • 2014
  • Background: The response to treatment and overall survival (OS) of patients with acute myeloid leukemia (AML) is variable, with a median ranging from 6 months to 11.5 years. TP53 is associated with old age, chemotherapy resistance, and worse OS. Using genetic sequencing, we set out to look at our own experience with AML, and hypothesized that both TP53 mutations and SNPs at codon 72 would mimic the literature by occurring in a minority of patients, and conferring a worse OS. Materials and Methods: We performed a pilot study of randomly selected, newly diagnosed AML patients at Mount Sinai Medical Center, diagnosed from 2005-2008 (n=10). TP53 PCR sequencing was performed using DNA from bone marrow smears. Analysis was accomplished using Mutation Surveyor software with confirmation of the variants using the COSMIC and dbSNP databases. Results: Fewer than half of the patients harbored TP53 mutations (40%). There was no significant difference in OS based on gender, AML history, risk-stratified karyotype, or TP53 mutation. There were possible trends toward improved survival among patients less than 60 (11 vs 4 months, p=0.09), Hispanics (8 vs 1 months, p=0.11), and those not harboring SNP P72R (8 vs 2 months, p=0.10). There was a significant improvement in survival among patients with better performance status (28 vs 4 months, p=0.01) and those who did not have a complex karyotype (8 vs 1 months, p=0.03). The most commonly observed TP53 mutation was a missense N310K (40%) and the most commonly observed SNP was P72R (100.0%). Conclusions: Our study confirms previous reports that poor PS and the presence of a complex karyotype are associated with a decreased OS. In our cohort, TP53 mutations were relatively common, occurring more frequently in male patients with an adverse karyotype. Although there was no significant difference in survival between TP53 mutated and un-mutated patients, there was a possible trend toward worse OS among patients with SNP P72R. Larger studies are needed to validate these findings.

Efficacy and Tolerability of Adjuvant Oral Capecitabine plus Intravenous Oxaliplatin (XELOX) in Asian Patients with Colorectal Cancer: 4-Year Analysis

  • Chiu, Joanne;Tang, Vikki;Leung, Roland;Wong, Hilda;Chu, Kin Wah;Poon, Jensen;Epstein, Richard J.;Yau, Thomas
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6585-6590
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    • 2013
  • Background: Although FOLFOX (infusional fluorouracil/leucovorin plus oxaliplatin) is established as a standard chemotherapeutic regimen, the long term efficacy of adjuvant XELOX (oral capecitabine plus intravenous oxaliplatin) in Asian colorectal cancer (CRC) patients remains anecdotal. Moreover, uncertainties persist as to whether pharmacogenetic differences in Asian populations preclude equally tolerable and effective administration of these drugs. Method: One hundred consecutive patients with resected colorectal cancer received adjuvant XELOX (oxaliplatin 130 $mg/m^2$ on day 1 plus capecitabine 900 $mg/m^2$ twice daily on day 1 to 14 every 3 weeks for 8 cycles) at Queen Mary Hospital, Hong Kong. Endpoints monitored during follow-up were disease-free survival (DFS) and disease recurrence, overall survival (OS) and adverse events (AEs). Results: The median patient age was 56 years, 56% were diagnosed with rectal cancer and 44% with colonic cancer. After a median follow-up of 4.3 years (95% confidence interval, 3.2-4.7), 24 recurrences were confirmed including 13 patients who died due to progressive disease. Four-year DFS was 81% in colon cancer patients and 67% in rectal cancer patients (p=0.06 by log-rank test). For the cohort as a whole, OS was 90% at 3 years and 84% at 5 years. Treatment-related AEs led to early withdrawal in four patients. The commonest non-hematological AEs were neuropathy (91%), hand-foot syndrome (49%) and diarrhea (46%), while the commonest grade 3/4 AEs were neutropenia (11%) and diarrhea (10%). Conclusion: These results confirm the favourable long term survival benefit with good tolerability in using adjuvant XELOX in treating East Asian colorectal cancer patients.

Pre-operative Predictive Factors for Intra-operative Pathological Lymph Node Metastasis in Rectal Cancers

  • Gao, Chun;Li, Jing-Tao;Fang, Long;Wen, Si-Wei;Zhang, Lei;Zhao, Hong-Chuan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6293-6299
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    • 2013
  • Background: A number of clinicopathologic factors have been found to be associated with pathological lymph node metastasis (pLNM) in rectal cancer; however, most of them can only be identified by expensive high resolution imaging or obtained after surgical treatment. Just like the Child-Turcotte-Pugh (CTP) and the model for end-stage liver disease (MELD) scores which have been widely used in clinical practice, our study was designed to assess the pre-operative factors which could be obtained easily to predict intra-operative pLNM in rectal cancer. Methods: A cohort of 469 patients who were treated at our hospital in the period from January 2003 to June 2011, and with a pathologically hospital discharge diagnosis of rectal cancer, were included. Clinical, laboratory and pathologic parameters were analyzed. A multivariate unconditional logistic regression model, areas under the curve (AUC), the Kaplan-Meier method (log-rank test) and the Cox regression model were used. Results: Of the 469 patients, 231 were diagnosed with pLNM (49.3%). Four variables were associated with pLNM by multivariate logistic analysis, age<60 yr (OR=1.819; 95% CI, 1.231-2.687; P=0.003), presence of abdominal pain or discomfort (OR=1.637; 95% CI, 1.052-2.547; P=0.029), absence of allergic history (OR=1.879; 95% CI, 1.041-3.392; P=0.036), and direct $bilirubin{\geq}2.60{\mu}mol/L$ (OR=1.540; 95% CI, 1.054-2.250; P=0.026). The combination of all 4 variables had the highest sensitivity (98.7%) for diagnostic performance. In addition, age<60 yr and direct $bilirubin{\geq}2.60{\mu}mol/L$ were found to be associated with prognosis. Conclusion: Age, abdominal pain or discomfort, allergic history and direct bilirubin were associated with pLNM, which may be helpful for preoperative selection.

Viral Hepatitis and Liver Cancer in Korea: an Epidemiological Perspective

  • Yeo, Yohwan;Gwack, Jin;Kang, Seokin;Koo, Boyeon;Jung, Sun Jae;Dhamala, Prakash;Ko, Kwang-Pil;Lim, Young-Khi;Yoo, Keun-Young
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6227-6231
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    • 2013
  • In the past, hepatitis B virus (HBV) infection was endemic in the general Korean population. The association of HBV infection with the occurrence of liver cancer has been well demonstrated in several epidemiologic studies. While the mortality rates of liver cancer in Korea have decreased steadily over the last decade, the presence of hepatitis B surface antigen (HBsAg) in mothers remains high at 3-4%, and 25.5% of these HBsAg positive mothers are positive for hepatitis B e antigen (HBeAg). HBV infection caused almost a quarter of hepatocellular carcinoma (HCC) cases and one-third of deaths from HCC. These aspects of HBV infection prompted the Korean government to create a vaccination program against HBV in the early 1980s. In 1995, the Communicable Disease Prevention Act (CDPA) was reformed, and the government increased the number of HBV vaccines in the National Immunization Program (NIP), driving the vaccination rate up to 95%. In 2000, the National Health Insurance Act (NHIA) was enacted, which provided increased resources for the prevention of perinatal HBV infection. Then in 2002, the Korean government, in conjunction with the Korean Medical Association (KMA), launched an HBV perinatal transmission prevention program. The prevalence of HBsAg in children had been high (4-5%) in the early 1980s, but had dropped to below 1% in 1995, and finally reached 0.2% in 2006 after the NIP had been implemented. After the success of the NIP, Korea finally obtained its first certification of achievement from the Western Pacific Regional Office of the World Health Organization (WPRO-WHO) for reaching its goal for HBV control. An age-period-cohort analysis showed a significant reduction in the liver cancer mortality rate in children and adolescents after the NIP had been implemented. In addition to its vaccination efforts, Korea launched the National Cancer Screening Program (NCSP) for 5 leading sites of cancer, including the liver, in 1999. As a consequence of this program, the 5-year liver cancer survival rate increased from 13.2% (1996-2000) to 23.3% (2003-2008). The development of both the primary and secondary prevention for liver cancer including HBV immunization and cancer screening has been of critical importance.

Evaluation of MT1XT20 Single Quasi-Monomorphic Mononucleotide Marker for Characterizing Microsatellite Instability in Persian Lynch Syndrome Patients

  • Farahani, Najmeh;Nikpour, Parvaneh;Emami, Mohammad Hassan;Hashemzadeh, Morteza;Zeinalian, Mehrdad;Shariatpanahi, Seyed Shervin;Salehi, Rasoul
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.9
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    • pp.4259-4265
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    • 2016
  • Background: Colorectal malignancies with high microsatellite instability (MSI-H), either hereditary (Lynch syndrome) or sporadic, demonstrate better prognosis and altered response to 5FU chemotherapy. It is now recommended to perform MSI testing for all new cases of colorectal cancer regardless of being categorized as hereditary or sporadic. For MSI detection, immunohistochemistry or PCR-based protocols using a cohort of various sets of STR markers are recommended. Here we aimed to evaluate a simplified protocol using just a single STR marker, MT1XT20 mononucleotide repeat, for detection of MSI in Lynch syndrome patients. A Promega five-marker MSI testing panel and immunohistochemistry (IHC) were used as the gold standard in conjunction with MT1XT20. Materials and Methods: Colorectal patients with a positive history of familial cancers were selected by evaluating medical records. Based on Amsterdam II criteria for Lynch syndrome 20 families were short listed. DNA was extracted from formalin fixed paraffin embedded tumour and adjacent normal tissues resected from the index case in each family. Extracted DNA was subjected to MT1XT20 mononucleotide marker analysis and assessment with a commercially available five marker MSI testing kit (Promega, USA). IHC also was performed on tissue sections and the results were compared with PCR based data. Results: Eight (40%), seven (35%) and five (25%) cases were MSI positive using with the Promega kit, IHC and MT1XT20, respectively. Among the markers included in Promega kit, BAT26 marker showed instability in all 8 samples. NR24 and NR21 markers showed instability in 7 (87.5%), and BAT25 and MONO 27 in 6 (75%) and 5 (62.5%). Conclusions: Although MT1XT20 was earlier reported as a valid standalone marker for MSI testing in CRC patients, we could not verify this in our Iranian patients. Instead BAT26 among the markers included in Promega MSI testing kit showed instability in all 8 MSI-H CRC samples. Therefore, it seems BAT26 could act well as a single marker for MSI testing in Iranian CRC patients.

Effect of Family Characteristics of the Baby Boomer Generation on the Level of Preparation for Old Age (베이비부머 세대의 가족 특성이 노후준비수준에 미치는 영향)

  • Park, Ju-Hee
    • Journal of Family Resource Management and Policy Review
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    • v.20 no.4
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    • pp.1-17
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    • 2016
  • The purpose of this study was to investigate the effect of family characteristics of the baby boomer generation on the level of their later life preparation. This study randomly sampled a birth cohort between 1955 and 1963 consisting of participants living in Seoul, South Korea with a spouse and a child/children. This study investigated a total of 455 subjects from March 2 to March 20, 2016. The study findings are summarized as follows. This study analyzed the characteristics of baby boomers' family relationships and their effects on their later life preparation. It was found that 55.4% of the subjects had at least 2 children, and 44.6% had 1 child. Concerning their children's marital status, 33.8% had married children and 66.2% had unmarried children. The level of their children's support was found at 2.82 points (standard deviation [SD] = .64), which is slightly higher than the mean value of 2.5. The spouse satisfaction among the subjects was found to be 3.59 (.79) which is higher than the mean value of 3. The general status of later life preparation was 2.70 (SD = .44), which is lower than the mean value of 3. In the sub-dimension, the level of social preparation was 2.98 points (SD = .61); the level of economic preparation was 2.60 (SD = .64); and the level of physical preparation was 2.53 (SD = .45). All the values were lower than the mean value of 3. The overall status of later life preparation of the subjects in this study was low. The physical preparation level was particularly low. To analyze the factors that affect baby boomers' later life preparation, a hierarchical regression analysis was implemented. As a result, a significant effect was found in specific factors, such as spouse satisfaction (${\beta}$ = .32, p < .001), age (${\beta}$ = .26, p < .001), number of children (${\beta}$ = -.18, p <.001), health status (${\beta}$ = .18, p < .001), gender (${\beta}$ = -.11, p < .05), household income (${\beta}$ = .10, p < .05), and children's marital status (${\beta}$ = .10, p < .05). That is, the higher the spousal satisfaction, the older the age, and the lower the number of children, the higher the levels of later life preparation. Further, a higher level of later life preparation was observed in women, those with higher household incomes, and those with married children.

Association of Single Nucleotide Polymorphism rs1053004 in Signal Transducer and Activator of Transcription 3 (STAT3) with Susceptibility to Hepatocellular Carcinoma in Thai Patients with Chronic Hepatitis B

  • Chanthra, Nawin;Payungporn, Sunchai;Chuaypen, Natthaya;Pinjaroen, Nutcha;Poovorawan, Yong;Tangkijvanich, Pisit
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.5069-5073
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    • 2015
  • The single nucleotide polymorphism (SNP) rs1053004 in Signal transducer and activator of transcription 3 (STAT3) was recently reported to be associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) in a Chinese cohort. This study was aimed at investigating whether the SNP might also contribute to HCC susceptibility in the Thai population. Study subjects were enrolled and divided into 3 groups including CHB-related HCC (n=211), CHB without HCC (n=233) and healthy controls (n=206). The SNP was genotyped using allelic discrimination assays based on TaqMan real-time PCR. Data analysis revealed that the distribution of different genotypes was in Hardy-Weinberg equilibrium (P>0.05). The frequencies of allele T (major allele) in HCC patients, CHB patients and healthy controls were 51.4%, 58.6% and 61.4%, respectively, whereas the frequencies of C allele (minor allele) were 48.6%, 41.4% and 38.6%. The C allele frequency was higher in HCC when compared with CHB patients (odds ratio (OR)=1.34, 95% confidence interval (CI)=1.02-1.74, P=0.032). The genotype of SNP rs1053004 (CC versus TT+TC) was significantly associated with an increased risk when compared with CHB patients (OR=1.83, 95% CI=1.13-2.99, P=0.015). In addition, we observed a similar trend of association when comparing HCC patients with healthy controls (OR=1.77, 95% CI=1.07-2.93, P=0.025) and all controls (OR=1.81, 95% CI=1.19-2.74, P=0.005). These findings suggest that the SNP rs1053004 in STAT3 might contribute to HCC susceptibility and could be used as a genetic marker for HCC in the Thai population.

Is there any Relationship between Food Habits in the Last Two Decades and Gastric Cancer in North-western Iran?

  • Somi, Mohammad Hossein;Mousavi, Seyed Mohsen;Naghashi, Shahnaz;Faramarzi, Elnaz;Jafarabadi, Mohammad Asghari;Ghojazade, Morteza;Majidi, Alireza;Alavi, Seyed Ahmad Naseri
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.1
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    • pp.283-290
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    • 2015
  • Purpose: The aims of this case-control study were to assess the correlation between some food habits in the last two decades and gastric cancer in East Azerbaijan of Iran. Materials and Methods: In this hospital based case control study, 616 patients (212 gastric cancer patients, 404 cancer free patients) were recruited. Food habits of patients over the past two decades were assessed with a structured questionnaire. We used conditional logistic regression analysis for estimating crude and adjusted odds ratios (OR) and their respective 95% confidence intervals (95%CI). Results: In this study, over-eating, consumption of high fat milk and yogurt and especial types of cheese increased the risk of gastric cancer (All<0.05). Consumption of such especial cheeses such as Koze and Khiki increased the risk of gastric cancer by 12.6 fold (95% CI:1.99-79.36) and 7.36 fold (95% CI:1.33-40.54), respectively. In addition, high fat food, moldy food, and pickled vegetables consumption as well as reuse of cooking oil for frying were significantly associated with gastric cancer risk. Furthermore, intake of Ghorme (deep fried meat) was positively correlated with gastric cancer risk (OR:1.31;95%CI: 0.91-1.87). Conclusions: It can be confirmed that particular food habits which have been very common in East-Azerbaijan in the last two past decades increase risk of gastric cancer. According to our results and taking into account the long latency period of gastric cancer it can be concluded that nutrition education for a healthy diet should be performed from early childhood. However, further well designed cohort studies are needed to achieve more clear results.

Analysis of CEA Expression and EGFR Mutation Status in Non-small Cell Lung Cancers

  • Yang, Zhong-Ming;Ding, Xian-Ping;Pen, Lei;Mei, Lin;Liu, Ting
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3451-3455
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    • 2014
  • Background: The serum carcinoembryonic antigen (CEA) level can reflect tumor growth, recurrence and metastasis. It has been reported that epidermal growth factor receptor (EGFR) mutations in exons 19 and 21may have an important relationship with tumor cell sensitivity to EGFR-TKI therapy. In this study, we investigated the clinical value of EGFR mutations and serum CEA in patients with non-small cell lung cancer (NSCLC). Materials and Methods: The presence of mutations in EGFR exons 19 and 21 in the tissue samples of 315 patients with NSCLC was detected with real-time fluorescent PCR technology, while the serum CEA level in cases who had not yet undergone surgery, radiotherapy, chemotherapy and targeted therapy were assessed by electrochemical luminescence. Results: The mutation rates in EGFR exons 19 and 21 were 23.2% and 14.9%, respectively, with the two combined in 3.81%. Measured prior to the start of surgery, radiotherapy, chemotherapy and targeted treatment, serum CEA levels were abnormally high in 54.3% of the patients. In those with a serum CEA level <5 ng/mL, the EGFR mutation rate was 18.8%, while with 5~19 ng/mL and ${\geq}20ng/mL$, the rates were 36.4% and 62.5%. In addition, in the cohort of patients with the CEA level being 20~49 ng/mL, the EGFR mutation rate was 85.7%, while in those with the CEA level ${\geq}50ng/mL$, the EGFR mutation rate was only 20.0%, approximately the same as in cases with the CEA level<5 ng/mL. Conclusions: There is a positive correlation between serum CEA expression level and EGFR mutation status in NSCLC patients, namely the EGFR mutation-positive rate increases as the serum CEA expression level rises within a certain range (${\geq}20ng/mL$, especially 20~49 ng/mL). If patient samples are not suitable for EGFR mutation testing, or cannot be obtained at all, testing serum CEA levels might be a simple and easy screening method. Hence, for the NSCLC patients with high serum CEA level (${\geq}20ng/mL$, especially 20~49 ng/mL), it is worthy of attempting EGFR-TKI treatment, which may achieve better clinical efficacy and quality of life.

A Time-series Study on Relationship between Visibility as an Indicator of Air Pollution and Daily Respiratory Mortality (대기오염 지표로서의 시정과 일별 호흡기계 사망간의 연관성에 관한 시계열적 연구)

  • Cho, Yong-Sung;Jung, Chang-Hoon;Son, Ji-Young;Chun, Young-Sin;Lee, Jong-Tae
    • Journal of Korean Society for Atmospheric Environment
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    • v.23 no.5
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    • pp.563-574
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    • 2007
  • There seems to be a consensus among most people that visibility impairment is the most obvious indicator of air pollution. While considerable evidence on the association between air pollution and health outcomes including death and disease have been established, based on industrial complex areas or huge urban cities, time-series, case-crossover and cohort studies, scarce literature exists on the direct evidence for the association between visibility and adverse health outcomes. Our study is assessed the effect of air pollution measured by visibility impairment on respiratory mortality over a period of six years. Relative risks in respiratory deaths were estimated by a Poisson regression model of daily deaths between $1999{\sim}2004$. Daily counts of respiratory deaths as dependent variable was modelled with daily 24-hr mean visibility measurements (kilometers) as independent variable by means of Poisson regression. This model is controlled for confounding factors such as day of weeks, weather variables, seasonal variables and $PM_{10}$. The results in this study is observed the statistically significant association between an inverse health effect and visibility during the study period for respiratory mortality (percentage change in the relative risk for all aged -0.57%, 95% Cl, $-1.01%{\sim}-0.12%$; for $0{\sim}15$ aged -7.12%, 95% Cl, $-13.29%{\sim}-0.51%$; for 65+ aged -0.43%, 95% Cl, $-0.93%{\sim}-0.06%$ per 1 km increased in visibility). The effect size was much reduced during warm season. Visibility impairment resulting from air pollution is strongly associated with respiratory mortality, especially for children may be spent at outdoor. Our result provides a quick and useful indicator for eliciting the contribution of air pollution to the excess risk of respiratory mortality in Seoul, Korea.