Jae Jeong Yang

Coinfection of hepatitis B and C viruses and risk of hepatocellular carcinoma: Systematic review and meta‐analysis

A subadditive effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is possible because superinfection of one virus tends to inhibit infection of the other virus. However, studies have reported inconsistent findings, and two meta‐analyses of studies from various countries (1998) and China (2005) reported a supraadditive effect for hepatocellular carcinoma (HCC) risk. Thus, we reevaluate HBV/HCV monoinfection and coinfection. Of 411 reports, we included 59 studies that assessed the association between HBV/HCV monoinfection and coinfection for HCC risk. HCC risk because of high/detectable HBV DNA and HBeAg infection was higher than HBsAg infection, whereas anti‐HCV vs anti‐HCV/HCV RNA was not different. Geographically, HCC risk was significantly higher in nonendemic than in HBV or HCV endemic areas. Subadditive effect for HCC risk was presented in recently published studies, cohort studies and studies conducted in HBV/HCV nonendemic areas; an additive effect was presented in studies conducted in HBV endemic areas; a supraadditive effect was presented in previously published studies, case‐control studies and studies conducted in HCV endemic areas. Our results suggest HBV/HCV coinfection for HCC risk is not significantly greater than HBV/HCV monoinfection, and HCC risk due to HBV or HCV is higher in nonendemic than endemic areas. The p‐heterogeneity was significant for most analyses, except HBV(+)/HCV(+) and HBV biomarker analyses. Prevention strategies targeted toward HBV or HCV monoinfected patients are needed. In addition, tailored prevention to reduce infectivity such as HBV markers (HBeAg, HBV DNA) is needed.

Isoflavones from Phytoestrogens and Gastric Cancer Risk: A Nested Case-Control Study within the Korean Multicenter Cancer Cohort

Background: The role of soybean products in gastric cancer risk is not clear in epidemiologic studies due to measurement error from dietary intake questionnaires and due to different degrees of bias according to study design. To examine the association between soybean products and gastric cancer risk, we measured phytoestrogen biological markers in a nested case-control study. Methods: The study population was composed of 131 cases and 393 matched controls within the Korean Multicenter Cancer Cohort. The concentrations of the four biomarkers in the plasma samples were measured using time-resolved fluoroimmunoassay. Conditional and unconditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence intervals (CI). Results: Median plasma concentrations of genistein (229 nmol/L for controls, 181.8 nmol/L for cases; P = 0.07) and daidzein (131.2 nmol/L for controls, 80.5 nmol/L for cases; P = 0.04) in cases were lower than in controls, whereas equol concentrations were similar. Compared with the reference group, gastric cancer risk decreased in the highest groups for genistein (OR, 0.54; 95% CI, 0.31-0.93) and daidzein (OR, 0.21; 95% CI, 0.08-0.58). Higher equol concentrations were associated with a decreased risk for gastric cancer (OR, 0.50; 95% CI, 0.27-0.90). The combination of the highest concentrations for each isoflavone category was associated with a 0.09-fold decreased risk for gastric cancer compared with the combination of the lowest concentrations for each category. There was no association between plasma lignan concentrations and gastric cancer. Conclusions: High serum concentrations of isoflavones were associated with a decreased risk for gastric cancer. Impact: These results suggest a beneficial effect of high soybean product intake for gastric cancer risk. Cancer Epidemiol Biomarkers Prev; 19(5); 1292–300. ©2010 AACR.

Lung cancer risk and cigarette smoking, lung tuberculosis according to histologic type and gender in a population based case-control study

We examined whether the strength of the association of cigarette smoking differs according to histological type and gender, and assessed other risk factors, in particular, tuberculosis. We recruited cases from the Korean Academy of Tuberculosis and Respiratory Diseases and controls from Chungju, a local site of the Korean Multi-Center Cancer Cohort. We matched one case to one control for females and two cases to one control for males according to age (<or=44, 45-69, and >or=70 years old). We used unconditional logistic regression to calculate the odds ratio (OR) and 95% confidence interval (CI) to estimate lung cancer risk by histologic type for males and females separately. The OR (95% CI) of 40 or more pack-years smoked relative to never smokers was 6.78 (4.17-11.00), 3.49 (1.83-6.33), and 2.72 (1.57-4.72) for males, and 13.72 (3.23-58.18), 12.18 (3.12-47.57), and 7.11 (1.78-28.43) for females for squamous cell, adenocarcinoma, and small cell carcinoma, respectively. Among males, the respective OR (95% CI) for past and current history of lung tuberculosis was 3.21 (2.12-4.90), 2.69 (1.63-4.45), and 1.52 (0.83-2.78), and for females was 2.40 (1.30-4.42), 4.20 (2.75-6.39), and 1.37 (0.61-3.06). Our findings provide additional evidence that women are more susceptible to the carcinogenic effects of tobacco, smoking has a higher risk for squamous cell and small cell carcinoma than adenocarcinoma, and tuberculosis is a potential risk factor for certain lung cancer histologic types.

The role of TNF genetic variants and the interaction with cigarette smoking for gastric cancer risk: a nested case-control study

BackgroundThe aim of this study was to investigate the role of TNF genetic variants and the combined effect between TNF gene and cigarette smoking in the development of gastric cancer in the Korean population.MethodsWe selected 84 incident gastric cancer cases and 336 matched controls nested within the Korean Multi-Center Cancer Cohort. Six SNPs on the TNF gene, TNF-α-238 G/A, -308 G/A, -857 C/T, -863 C/A, -1031 T/C, and TNF-β 252 A/G were genotyped. The ORs (95% CIs) were calculated using unconditional logistic regression model to detect each SNP and haplotype-pair effects for gastric cancer. The combined effects between the TNF gene and smoking on gastric cancer risk were also evaluated. Multi dimensionality reduction (MDR) analyses were performed to explore the potential TNF gene-gene interactions.ResultsTNF-α-857 C/T containing the T allele was significantly associated with an increased risk of gastric cancer and a linear trend effect was observed in the additive model (OR = 1.6, 95% CI 1.0–2.5 for CT genotype; OR = 2.6, 95% CI 1.0–6.4 for TT genotype). All haplotype-pairs that contained TCT or CCC of TNF-α-1031 T/C, TNF-α-863 C/A, and TNF-α-857 C/T were associated with a significantly higher risk for gastric cancer only among smokers. In the MDR analysis, regardless of smoking status, TNF-α-857 C/T was included in the first list of SNPs with a significant main effect.ConclusionTNF-α-857 C/T polymorphism may play an independent role in gastric carcinogenesis and the risk for gastric cancer by TNF genetic effect is pronounced by cigarette smoking.

Soybean Product Intake Modifies the Association between Interleukin-10 Genetic Polymorphisms and Gastric Cancer Risk

In this study, our aim was to investigate the association of inflammation-related genetic polymorphisms and gastric cancer risk and to examine whether the combined effect of soybean product intake modified cancer risk. Eighty-four incident gastric cancer cases and 336 matched controls were selected from the Korean Multi-Center Cancer Cohort. We selected 14 single nucleotide polymorphisms (SNP) from 5 genes [interleukin (IL)-1beta, IL-2, IL-4, IL-8, and IL-10] and used unconditional logistic regression model to calculate the odds ratios (OR) and 95% CI adjusting for H. pylori seropositivity, smoking, age, sex, enrollment year, and residential area. The risk for gastric cancer in relation to genetic polymorphisms and haplotypes were assessed according to soybean product intake levels. Although no single SNP effect was found, the combined effect between IL-10 gene variants of -592 GG/GA, -819 TC/CC, or -1082 AG/GG and low intake of soybean products had an increased risk for gastric cancer compared with the group with no risk gene variants and a high intake of soybean products (OR [95% CI] = 2.82 [1.04-7.62], 2.75 [1.02-7.44], and 4.34 [1.51-12.5], respectively). Among the low-soybean product intake group, IL-10 CCG haplotype had an increased risk of gastric cancer (OR = 3.38 [1.40-8.13]) relative to the ATA haplotype. Our results suggest that the association between IL-10 genetic polymorphisms and gastric cancer risk was modified by soybean product intake.

Comparative estimation of coverage between national immunization program vaccines and non-NIP vaccines in Korea.

This study aimed to describe the differences in vaccination coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Korea and to identify factors affecting the difference. Nationwide face-to-face interview-based questionnaire survey among randomly selected 4,374 participants aged 7-83 months was conducted. Vaccination coverage analyzed according to the birth cohorts, geographic areas, and socio-demographic characteristics. We found that NIP vaccines recorded higher primary vaccination coverage compared to non-NIP vaccines (95.9%-100% vs 30.7%-85.4%). The highest rate was Haemophilus influenzae type b (Hib) vaccine (85.4%), which was introduced in 1996, and the lowest rate was rotavirus vaccine (30.7%), which was introduced recently. On multivariate analysis, having a sibling were significantly associated with lower uptake of Hib vaccine, pneumococcal conjugate vaccine (PCV), and rotavirus vaccine; while, older mothers age and attendance to daycare center were significantly associated with lower uptake of PCV and rotavirus vaccine (P < 0.001). We found differences in the vaccine coverage rate between NIP vaccines and non-NIP vaccines; and the data suggests potential disparity in accessing non-NIP vaccines in Korea. Expansion of NIP to include non-NIP vaccines can provide better protection against the diseases through increased coverage.

Intake of Soy Products and Other Foods and Gastric Cancer Risk: A Prospective Study

Background Gastric cancer, the most common cancer in the world, is affected by some foods or food groups. We examined the relationship between dietary intake and stomach cancer risk in the Korean Multi-Center Cancer Cohort (KMCC). Methods The KMCC included 19 688 Korean men and women who were enrolled from 1993 to 2004. Of those subjects, 9724 completed a brief 14-food frequency questionnaire at baseline. Through record linkage with the Korean Central Cancer Registry and National Death Certificate databases, we documented 166 gastric cancer cases as of December 31, 2008. Cox proportional hazard models were used to estimate relative risks (RRs) and 95% CIs. Results Frequent intake of soybean/tofu was significantly associated with reduced risk of gastric cancer, after adjustment for age, sex, cigarette smoking, body mass index, alcohol consumption, and area of residence (P for trend = 0.036). We found a significant inverse association between soybean/tofu intake and gastric cancer risk among women (RR = 0.41, 95% CI: 0.22–0.78). Men with a high soybean/tofu intake had a lower risk of gastric cancer, but the reduction was not statistically significant (RR = 0.77, 95% CI: 0.52–1.13). There was no interaction between soybean/tofu intake and cigarette smoking in relation to gastric cancer risk (P for interaction = 0.268). Conclusions Frequent soybean/tofu intake was associated with lower risk of gastric cancer.

Estimation of Nationwide Vaccination Coverage and Comparison of Interview and Telephone Survey Methodology for Estimating Vaccination Status

This study compared interview and telephone surveys to select the better method for regularly estimating nationwide vaccination coverage rates in Korea. Interview surveys using multi-stage cluster sampling and telephone surveys using stratified random sampling were conducted. Nationwide coverage rates were estimated in subjects with vaccination cards in the interview survey. The interview survey relative to the telephone survey showed a higher response rate, lower missing rate, higher validity and a less difference in vaccination coverage rates between card owners and non-owners. Primary vaccination coverage rate was greater than 90% except for the fourth dose of DTaP (diphtheria/tetanus/pertussis), the third dose of polio, and the third dose of Japanese B encephalitis (JBE). The DTaP4: Polio3: MMR1 fully vaccination rate was 62.0% and BCG1:HepB3:DTaP4:Polio3:MMR1 was 59.5%. For age-appropriate vaccination, the coverage rate was 50%-80%. We concluded that the interview survey was better than the telephone survey. These results can be applied to countries with incomplete registry and decreasing rates of landline telephone coverage due to increased cell phone usage and countries. Among mandatory vaccines, efforts to increase vaccination rate for the fourth dose of DTaP, the third dose of polio, JBE and regular vaccinations at recommended periods should be conducted in Korea.

Validation of self-reported cancer incidence at follow-up in a prospective cohort study.

Self-reported cancer is a valuable epidemiological tool for identifying cases in cohort studies. The cost, time, and resources required, in addition to the efficiency in ascertaining cases, need to be considered when deciding between active and passive follow-up approaches. Because Korean families hold a family-centered approach when making decisions (1), it is not uncommon for patients to be unaware of their cancer diagnosis or status. A total of 20% of physicians and 33% of family members opposed patient notification of his or her disease status (2), and only 35% of Korean-Americans would tell a patient about a terminal prognosis (1). Because of these cultural differences and, thus, inaccuracies in self-reported information that arise, there is a need to examine the appropriateness of the active follow-up

Oncogenic CagA promotes gastric cancer risk via activating ERK signaling pathways: a nested case-control study.

Background CagA cellular interaction via activation of the ERK signaling pathway may be a starting point in the development of gastric cancer. This study aimed to evaluate whether genes involved in ERK downstream signaling pathways activated by CagA are susceptible genetic markers for gastric cancer. Methods In the discovery phase, a total of 580 SNPs within +/−5 kbp of 30 candidate genes were genotyped to examine an association with gastric cancer risk in the Korean Multi-center Cancer Cohort (100 incident gastric cancer case-control sets). The most significant SNPs (raw or permutated p value<0.02) identified in the discovery analysis were re-evaluated in the extension phase using unconditional logistic regression model (400 gastric cancer case-control sets). Combined analyses including pooled- and meta-analysis were conducted to summarize all the results. Results 24 SNPs in eight genes (ERK, Dock180, C3G, Rap1, Src, CrkL, Mek and Crk) were significantly associated with gastric cancer risk in the individual SNP analyses in the discovery phase (p<0.05). In the extension analyses, ERK rs5999749, Dock180 rs4635002 and C3G rs7853122 showed marginally significant gene-dose effects for gastric cancer. Consistently, final combined analysis presented the SNPs as significantly associated with gastric cancer risk (OR = 1.56, [95% CI: 1.19–2.06], OR = 0.61, [95% CI: 0.43–0.87], OR = 0.59, [95% CI: 0.54–0.76], respectively). Conclusions Our findings suggest that ERK rs5999749, Dock180 rs4635002 and C3G rs7853122 are genetic determinants in gastric carcinogenesis.