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Purpose - Few studies investigated roles of body mass index (BMI) on gastric cancer (GC) risk according to Helicobacter pylori infection status. This study was conducted to evaluate associations between BMI and GC risk with consideration of H. pylori infection information. Materials and Methods - We performed a case-cohort study (n=2,458) that consists of a subcohort, (n=2,193 including 67 GC incident cases) randomly selected from the Korean Multicenter Cancer Cohort (KMCC) and 265 incident GC cases outside of the subcohort. H. pylori infection was assessed using an immunoblot assay. GC risk according to BMI was evaluated by calculating hazard ratios (HRs) and their 95% confidence intervals (95% CIs) using weighted Cox hazard regression model. Results - Increased GC risk in lower BMI group (< 23 kg/m2) with marginal significance, (HR, 1.32; 95% CI, 0.98 to 1.77) compared to the reference group (BMI of 23-24.9 kg/m2) was observed. In the H. pylori non-infection, both lower (< 23 kg/m2) and higher BMI (≥ 25 kg/m2) showed non-significantly increased GC risk (HR, 10.82; 95% CI, 1.25 to 93.60 and HR, 11.33; 95% CI, 1.13 to 113.66, respectively). However, these U-shaped associations between BMI and GC risk were not observed in the group who had ever been infected by H. pylori. Conclusion - This study suggests the U-shaped associations between BMI and GC risk, especially in subjects who had never been infected by H. pylori.

This Series paper describes the current state of cancer control in Pacific island countries and territories (PICTs). PICTs are diverse but face common challenges of having small, geographically dispersed, isolated populations, with restricted resources, fragile ecological and economic systems, and overburdened health services. PICTs face a triple burden of infection-related cancers, rapid transition to lifestyle-related diseases, and ageing populations; additionally, PICTs are increasingly having to respond to natural disasters associated with climate change. In the Pacific region, cancer surveillance systems are generally weaker than those in high-income countries, and patients often present at advanced cancer stage. Many PICTs are unable to provide comprehensive cancer services, with some patients receiving cancer care in other countries where resources allow. Many PICTs do not have, or have poorly developed, cancer screening, pathology, oncology, surgical, and palliative care services, although some examples of innovative cancer planning, prevention, and treatment approaches have been developed in the region. To improve cancer outcomes, we recommend prioritising regional collaborative approaches, enhancing cervical cancer prevention, improving cancer surveillance and palliative care services, and developing targeted treatment capacity in the region.

Purpose Despite the low mortality rate of breast cancer among women in Korea, the breast cancer mortality rate has increased. The aim of this study was to examine trends in breast cancer mortality from 1983 to 2012 in Korea, assessing the importance of age, period, and birth cohort as risk factors. Materials and Methods Data on the annual number of deaths due to female breast cancer and on female population statistics from 1983 to 2012 were obtained from Statistics Korea. A log-linear Poisson age-period-cohort model was used to estimate age, period, and cohort effects. Results The increasing breast cancer mortality can be explained predominantly by a birth cohort effect: the risk of breast cancer death showed a steady increase until the 1968 birth cohort, and decreased thereafter. There was a sharp increase in the magnitude of the age effect up to 60 years old, then a moderate increase in the effect during the sixties, followed by another sharp increase from 70 years old. The period effect on breast cancer mortality seems negligible based on its adjusted relative risk, even though it was statistically significant after adjusting for age and cohort effects. Conclusion In this study, the mortality pattern of breast cancer in Korea can be explained predominantly by a birth cohort effect. Hence, the overall mortality rate of breast cancer may increase for a while, and show a gradual decrease in the future, which will start from the younger age group.

Previous cohort studies have demonstrated a positive association between diabetes mellitus (DM) and colorectal cancer (CRC). However, there are few comparisons between DM groups categorized by fasting glucose level. This study examined associations between diabetes as defined by fasting glucose level and self-reported history of DM and CRC risk among Korean adults. Data from the Korean Multi-center Cancer Cohort between 1993 and 2005 were analyzed. The study population comprised 14,570 participants aged 20 years or older. Participants were followed until December 31, 2012 (median follow-up: 11.9 years). Among participants with high fasting glucose (≥126mg/dL), the risk of developing CRC was significantly higher (HR: 1.51 [1.02-2.25]) than among participants with low fasting glucose (

Knowledge about human papillomaviruses (HPV) types involved in anal cancers in some world regions is scanty. Here, we describe the HPV DNA prevalence and type distribution in a series of invasive anal cancers and anal intraepithelial neoplasias (AIN) grades 2/3 from 24 countries. We analyzed 43 AIN 2/3 cases and 496 anal cancers diagnosed from 1986 to 2011. After histopathological evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping was performed using SPF-10/DEIA/LiPA25 system (version 1). A subset of 116 cancers was further tested for p16(INK4a) expression, a cellular surrogate marker for HPV-associated transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance in the anal cancer data set. HPV DNA was detected in 88.3% of anal cancers (95% confidence interval [CI]: 85.1-91.0%) and in 95.3% of AIN 2/3 (95% CI: 84.2-99.4%). Among cancers, the highest prevalence was observed in warty-basaloid subtype of squamous cell carcinomas, in younger patients and in North American geographical region. There were no statistically significant differences in prevalence by gender. HPV16 was the most frequent HPV type detected in both cancers (80.7%) and AIN 2/3 lesions (75.4%). HPV18 was the second most common type in invasive cancers (3.6%). p16(INK4a) overexpression was found in 95% of HPV DNA-positive anal cancers. In view of the results of HPV DNA and high proportion of p16(INK4a) overexpression, infection by HPV is most likely to be a necessary cause for anal cancers in both men and women. The large contribution of HPV16 reinforces the potential impact of HPV vaccines in the prevention of these lesions.

Chronic Hepatitis B (HB) is the main risk factor for chronic liver disease (CLD) and hepatocellular carcinoma (HCC) in many low-resource countries, where diagnosis is constrained by lack of clinical, histopathological and biomarker resources. We have used proteomics to detect plasma biomarkers that outperform α-Fetoprotein (AFP), the most widely used biomarker for HCC diagnosis in low-resource contexts. Deep-plasma proteome analysis was performed in HCC patients, patients with CLD and in HB-carrier controls from Thailand (South-East Asia) and The Gambia (West-Africa). Mass spectrometry profiling identified latent-transforming growth factor β binding-protein 2 (LTBP2) and Osteopontin (OPN) as being significantly elevated in HCC versus CLD and controls. These two proteins were further analyzed by ELISA in a total of 684 plasma samples, including 183 HCC, 274 CLD and 227 asymptomatic controls. When combined, LTBP2 and OPN showed an area under the receiver operating curve of 0.85 in distinguishing HCC from CLD in subjects with AFP

Summary Background & aims To evaluate the relationship between phytoestrogen and colon cancer risk, we quantified plasma isoflavones (Genistein and Daidzein) and lignan (enterolactone) in a Korean nested case-control study and conducted replication study in a Vietnamese case-control study. Methods Study populations of 101 cases and 391 controls were selected from the Korean Multicenter Cancer Cohort which was constructed from 1993 to 2004. For replication study, Vietnamese hospital-based case-control subjects of 222 cases and 206 controls were selected from 2003 to 2007. The concentrations of plasma genistein, daidzein, and enterolactone were quantified by liquid chromatography-mass spectrometry. Logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs), and meta-analysis was conducted to estimate combined ORs (CORs) and 95% Cis of Korean and Vietnamese population in 2014. Results Genistein showed a continual decrease in colorectal cancer risk according to level up of the concentration categories in Korean and Vietnamese population ( P for trend = 0.032, and 0.001, respectively) and a significantly decreased risk was found at the highest concentration of genistein and daidzein (for the highest category compared to the lowest: COR (95% CI) = 0.46 (0.30–0.69), and COR (95% CI) = 0.54 (0.36–0.82)). When the study population was stratified, the beneficial relationship of genistein with colorectal cancer was observed regardless of sex and anatomical subtype. However, enterolacton level was not associated with colorectal cancer risk. Conclusions High plasma levels of isoflavones had relationship with a decreased risk of colorectal cancer, regardless of different ethnic background.

Background Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia. Objective To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16 INK4a ) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included. Design, setting, and participants After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using the SPF-10/DEIA/LiPA 25 system, v.1 (Laboratory Biomedical Products, Rijswijk, The Netherlands). HPV DNA–positive cases were additionally tested for oncogene E6*I mRNA and all cases for p16 INK4a expression, a surrogate marker of oncogenic HPV activity. Outcome measurements and statistical analysis HPV DNA prevalence and type distributions were estimated. Results and limitations HPV DNA was detected in 33.1% of penile cancers (95% confidence interval [CI], 30.2–36.1) and in 87.1% of HGSILs (95% CI, 78.0–93.4). The warty-basaloid histologic subtype showed the highest HPV DNA prevalence. Among cancers, statistically significant differences in prevalence were observed only by geographic region and not by period or by age at diagnosis. HPV16 was the most frequent HPV type detected in both HPV-positive cancers (68.7%) and HGSILs (79.6%). HPV6 was the second most common type in invasive cancers (3.7%). The p16 INK4a upregulation and mRNA detection in addition to HPV DNA positivity were observed in 69.3% of HGSILs, and at least one of these HPV activity markers was detected in 85.3% of cases. In penile cancers, these figures were 22.0% and 27.1%, respectively. Conclusions About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV activity marker, respectively. The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines in the reduction of HPV-related penile neoplastic lesions. Patient summary About one-third to one-quarter of penile cancers were related to human papillomavirus (HPV). The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines to prevent HPV-related penile neoplastic lesions.

Supplemental Digital Content is available in the text, We conducted a heterogeneous risk assessment of breast cancer based on the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) calculating the risks and population-based attributable fractions (PAFs) for modifiable and nonmodifiable factors. Using matched case–control study design from the Seoul Breast Cancer Study and the national prevalence of exposure, the risks and PAFs for modifiable and nonmodifiable factors were estimated for total breast cancers and subtypes. The attribution to modifiable factors was different for each subtype (luminal A, PAF = 61.4% [95% confidence interval, CI = 54.3%–69.8%]; luminal B, 21.4% [95% CI = 18.6–24.9%]; HER2-overexpression, 59.4% [95% CI = 47.8%–74.3%], and triple negative tumors [TNs], 27.1% [95% CI = 22.9%–32.4%)], and the attribution to the modifiable factors for the luminal A and HER2-overexpression subtypes was higher than that of the luminal B and TN subtypes (P heterogeneity ≤ 0.001). The contribution of modifiable reproductive factors to luminal A type in premenopausal women was higher than that of the other subtypes (18.2% for luminal A; 3.1%, 8.1%, and −3.1% for luminal B, HER2-overexpression, and TN subtypes, respectively; P heterogeneity ≤ 0.001). Physical activity had the highest impact preventing 32.6% of luminal A, 14.5% of luminal B, 38.0% of HER2-overexpression, and 26.9% of TN subtypes (P heterogeneity = 0.014). Total reproductive factors were also heterogeneously attributed to each breast cancer subtype (luminal A, 65.4%; luminal B, 24.1%; HER2-overexpression, 57.9%, and TN subtypes, −3.1%; P heterogeneity ≤ 0.001). Each pathological subtype of breast cancer by HRs and HER2 status may be associated with heterogeneous risk factors and their attributable risk, suggesting a different etiology. The luminal B and TN subtypes seemed to be less preventable despite intervention for alleged risk factors, even though physical activity had a high preventable potential against breast cancer.

Breast and ovarian cancers are predominant female cancers with increasing prevalence. The purpose of this study was to estimate the population attributable risks (PARs) of breast and ovarian cancer occurrence based on the relative risks (RRs) of modifiable reproductive factors and population-specific exposure prevalence.The PAR was calculated by using the 1990 standardized prevalence rates, the 2010 national cancer incidence with a 20 year lag period, the meta-analyzed RRs from studies conducted in the Korean population for breast cancer, and the meta-analyzed RRs from a Korean epithelial ovarian cancer study and a prior meta-analysis, and ovarian cancer cohort results up to 2012. For oral contraceptive and hormone replacement therapy use, we did not consider lag period.The summary PARs for modifiable reproductive factors were 16.7% (95% CI 15.8-17.6) for breast cancer (2404 cases) and 81.9% (95% CI 55.0-100.0) for ovarian cancer (1579 cases). The modifiable reproductive factors included pregnancy/age at first birth (8.0%), total period of breastfeeding (3.1%), oral contraceptive use (5.3%), and hormone replacement therapy use (0.3%) for breast cancer and included breastfeeding experience (2.9%), pregnancy (1.2%), tubal ligation (24.5%), and oral contraceptive use (53.3%) for ovarian cancer.Despite inherent uncertainties in the risk factors for breast and ovarian cancers, we suggest that appropriate long-term control of modifiable reproductive factors could reduce breast and ovarian cancer incidences and their related burdens by 16.7% and 81.9%, respectively.

This study was conducted to evaluate the relevance of the soluble form of c-Met protein, a truncated form of the c-Met membrane receptor involved in the CagA pathway, as a potential biomarker for gastric cancer. Among 290 gastric cancer case-control sets selected from the Korean Multicenter Cancer Cohort, the plasma concentrations of soluble c-Met protein were measured with enzyme-linked immunosorbent assays. Using analysis of variance and covariance models with age, sex, smoking, Helicobacter pylori infection, and CagA seropositivity, the mean concentrations of soluble c-Met protein between cases and controls were compared. To evaluate the association between gastric cancer and a c-Met protein level, odds ratios and 95% confidence intervals were estimated using conditional logistic regression models. Interactions between CagA-related genes and the soluble c-Met protein concentration were also investigated. The overall median plasma concentration of soluble c-Met among cases was significantly lower than those of controls (1.390 vs. 1.610 ng/mL, p < 0.0001). Closer to the onset of gastric cancer, the soluble c-Met protein level decreased linearly in a time-dependent manner (p for trend = 0.0002). The combined effects between the CagA-related genes and the soluble c-Met protein concentration significantly intensified risks for gastric cancer. Restricted analyses including cases that had been diagnosed within 1 year after entering the cohort had a fair degree of ability (area under the receiver operating characteristic curve of 0.73-0.77) to discriminate gastric cancer cases from normal controls. Our findings demonstrate the potential of the soluble form of c-Met protein as a novel biomarker for gastric cancer. The beneficial effects of a high soluble c-Met concentration in human plasma are strongly supported.

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.

Incidence of breast cancer is rising in Asian countries, and breast cancer is the most common cancer among Asian women. However, there are few recent descriptive reports on the epidemiology of breast cancer among Eastern and Southeastern Asian populations.We examined incidence trends for invasive breast cancer in women aged ≥20 years from 15 registries in Eastern (China, Japan, the Republic of Korea, Taiwan) and Southeastern Asia (the Philippines, Singapore, Thailand) for the period 1993-2002 mainly using data from Cancer Incidence in Five Continents, Volumes VIII and IX. We compared trends in annual incidence rates and age-specific incidence curves over a 10-year period. We also compared the incidence rates of Asian-Americans with the rates of their Asian counterparts.Breast cancer incidence rates increased gradually over time in all study populations. Rates were relatively high in Southeastern Asia and became progressively lower along a south-to-north gradient, with a fourfold geographic variation within the study populations. Age-specific incidence curves showed patterns that gradually changed according to incidence rates. Breast cancer incidence among Asian women living in the United States was 1.5-4 times higher than the corresponding incidence rate in the women's respective countries of origin.Breast cancer incidence is expected to continue to increase for the next 10 years in Asia and may approach rates reported among Asian-Americans. The number and mean age of breast cancer cases is expected to increase as the female Asian population ages, the prevalence of certain risk factors changes (early menarche, late menopause, low parity, late age at first live birth, and low prevalence of breastfeeding), and as Asian countries introduce mass screening programs.

The Cancer Incidence in Five Continents (CI5) series comprises nine volumes that bring together peer-reviewed results from population-based cancer registries worldwide. The aim of each is to make available comparable data on cancer incidence from as wide a range of geographical locations as possible. In addition, the existence of long time series of data allows the evolution of risk in different populations over time to be studied. The CI5 I-IX database brings together the results from all nine volumes, spanning a period of some 50 years. In addition, unpublished annual data, with more diagnostic detail, are made available for many cancer registries with 15 or more years of recent data. We describe the construction and composition of the CI5 databases, and provide examples of how they can be used to prepare tables and graphs comparing incidence rates between populations. This is the classical role of descriptive statistics: to allow formulation of hypotheses that might explain the observed differences (geographically, over time, in population subgroups) and that can be tested by further study. Such statistics are also essential components in the planning and evaluation of cancer control programmes.

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.

CHFR was recently identified as an early mitotic checkpoint that delays transition to metaphase in response to mitotic stress. Although studies have shown that CHFR is relevant to tumorigenesis, no previous report has investigated whether polymorphisms in the CHFR gene are associated with the risk of cancer development. Here, we genotyped polymorphisms in the CHFR gene and analyzed the possible associations of single polymorphisms and haplotypes with the risk and clinicopathological characteristics of colorectal cancer. Six coding SNPs in the CHFR gene were genotyped in 462 colorectal cancer patients and 245 healthy normal controls, using either the TaqMan assay or direct sequencing. Our results revealed that the V539M polymorphism was significantly associated with a lower risk of colorectal cancer (P=0.03; OR, 0.533; 95% CI, 0.302-0.94), and significantly correlated with no distant metastasis (M0 stage), different TNM stage, and microsatellite instability (MSI) among the colorectal cancer patients. Among the five tested haplotypes, hap 10 (TGACTA) was significantly associated with a lower risk of colorectal cancer (P=0.017; OR, 0.496; 95% CI, 0.279-0.883), and colorectal cancer patients carrying this haplotype showed no distant metastasis, different TNM stage, and microsatellite instability at a significantly higher frequency. These results reveal for the first time that polymorphisms in the CHFR gene are associated with colorectal cancer susceptibility.

Background Breast and ovarian cancers are predominant female cancers with increasing prevalence. The purpose of this study was to estimate the population attributable risks (PARs) of breast and ovarian cancer occurrence based on the relative risks (RRs) of modifiable reproductive factors and population-specific exposure prevalence. Methods The PAR was calculated by using the 1990 standardized prevalence rates, the 2010 national cancer incidence with a 20 year lag period, the meta-analyzed RRs from studies conducted in the Korean population for breast cancer, and the meta-analyzed RRs from a Korean epithelial ovarian cancer study and a prior meta-analysis, and ovarian cancer cohort results up to 2012. For oral contraceptive and hormone replacement therapy use, we did not consider lag period. Results The summary PARs for modifiable reproductive factors were 16.7 % (95 % CI 15.8–17.6) for breast cancer (2404 cases) and 81.9 % (95 % CI 55.0–100.0) for ovarian cancer (1579 cases). The modifiable reproductive factors included pregnancy/age at first birth (8.0 %), total period of breastfeeding (3.1 %), oral contraceptive use (5.3 %), and hormone replacement therapy use (0.3 %) for breast cancer and included breastfeeding experience (2.9 %), pregnancy (1.2 %), tubal ligation (24.5 %), and oral contraceptive use (53.3 %) for ovarian cancer. Conclusions Despite inherent uncertainties in the risk factors for breast and ovarian cancers, we suggest that appropriate long-term control of modifiable reproductive factors could reduce breast and ovarian cancer incidences and their related burdens by 16.7 % and 81.9 %, respectively. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-2040-0) contains supplementary material, which is available to authorized users.

Cervical cancer is a major health problem for Korean women, accounting for 9.8% of new female cancer cases, even though incidence rates have been decreasing. The Korean cervical cancer mortality rate for 1993-2002 based on National Statistical Office data shows an increasing trend, but the actual rates are thought to have decreased by epidemiologists, clinicians and other cancer experts. To explain this gap and solve this problem, we corrected the number of cervical cancer deaths by comparing death certificate cases of unspecified uterine cancer data with the national cancer incidence databases of entire cancer registries in Korea. We used 2 different methods to make a correction. First, we considered "uterus, unspecified" deaths previously registered as "cervix, uterine" cases misclassified and added them to the cervical cancer deaths. Alternatively, we multiplied the total number of registered unspecified uterine cancer deaths by age-specific proportions of registered incident cervical cancer cases among all cancers and added the product to cervical cancer deaths. The overall corrected age-standardized cervical cancer mortality rates per 100,000 women decreased from 5.2 in 1993 to 3.9 in 2002 (estimated annual percentage change (EAPC): -4.05%, 95% CI: -4.88, -3.22). While cervical cancer mortality showed a decreasing tendency in women aged 30-69 years, it increased substantially in women aged > or =70 years (EAPC: 3.62%, 95% CI: 1.92-5.35). Results of this study will provide evidence-based foundation for the evaluation of the existing cervical cancer-screening programs.

We investigated the risk of gastric cancer by subsite in relation to cigarette smoking and alcohol in a large population-based cohort of 669 570 Korean men in an insurance plan followed for an average 6.5 years, yielding 3452 new cases of gastric cancer, of which 127 were cardia and upper-third gastric cancer, 2409 were distal gastric cancer and 1007 were unclassified. A moderate association was found between smoking, cardia and upper-third (adjusted relative risk (aRR) 2.2; 95% confidence interval (CI) 1.4-3.5) and distal cancers (aRR=1.4; 95% CI=1.3-1.6). We also found a positive association between alcohol consumption and distal (aRR=1.3; 95% CI=1.2-1.5) and total (aRR=1.2; 95% CI=1.1-1.4) gastric cancer. Combined exposure to high levels of tobacco and alcohol increased the risk estimates further; cardia and upper-third gastric cancers were more strongly related to smoking status than distal gastric cancer.British Journal of Cancer (2007) 97, 700-704. doi:10.1038/sj.bjc.6603893 www.bjcancer.com Published online 17 July 2007.

Cancer is primarily a disease of older adults. However, little data is available on the clinical features of cervical cancer in elderly patients. We investigated the trends in incidence and clinical features associated with cervical cancer among the elderly in Korea during the period of 1993-2002. We obtained data from the National Cervical Cancer Incidence Database, which was constructed in collaboration with the Korea Central Cancer Registry (KCCR) and Korea Gynecologic Cancer Registry (KGCR). A total of 44 191 women with cervical cancer were diagnosed between 1993 and 2002. Patients were divided into three groups based on age:/=49 years (Group 1), 50-69 years (Group 2), and/=70 years (Group 3). During this period, upward incidence trends were noted in Group 3 while constant and downward incidence trends were noted in Groups 1 and 2, respectively. Pooled analysis across years revealed that squamous cell carcinoma and advanced stage (IIB, III, and IV) were more common in Group 3 than in Groups 1 and 2. With regard to primary treatments in the elderly patients, surgery appeared to be performed increasingly despite the fact that advanced stage (IIB, III, and IV) was more common in Group 3 than in Groups 1 and 2. Our findings suggest that the incidence of cervical cancer in the elderly is increasing in Korea, while it is decreasing overall. The current health service must emphasize education for the elderly about cervical cancer prevention while concentrating on screening.

BACKGROUND: Little is known about the genetic risk factors associated with colorectal cancer. Although the Ser326Cys polymorphism of 8-oxoguanine DNA glycosylase (hOGG1) is consistently associated with a range of cancers, there is no consensus regarding this polymorphism and colorectal cancer risk.METHODS: In the present study, conducted in a Korean population, we used the TaqMan assay to investigate whether the hOGG1 Ser326Cys polymorphism was associated with colorectal cancer in 439 colorectal cancer patients and 676 healthy normal controls. We also examined whether the hOGG1 Ser326Cys polymorphism is associated with tumor location, microsatellite instability (MSI) status and tumor-node-metastasis (TNM) stage in colorectal cancer.RESULTS: We found no significant difference between the cancer and control populations in terms of genotype distribution (CC, CG and GG). In addition, we found no association between the hOGG1 Ser326Cys polymorphism and cancer risk, MSI status, TNM stage or tumor location in colorectal cancer patients.CONCLUSIONS: These results suggest that unlike for other cancer types, the hOGG1 Ser326Cys polymorphism is not a major genetic risk factor for colorectal cancer.J Epidemiol 2007; 17: 156-160.

The death rate of liver cancer in Korea has been reported as one of the highest in the world. This study was conducted to investigate geographical variations of liver cancer mortality in Korea in order to obtain insight into possible environmental factors related to liver cancer.The sex-specific standardized mortality ratios (SMRs) of liver cancer were calculated for 168 basic administrative units in Korea based upon the vital statistics for the seven years 1992 to 1998, as well as the sex- and age-specific population of each area for 1995. The SMRs were classified into six categories and depicted on a map for each sex.The southern provinces showed clearly higher mortality rates as compared to the rest of the country in both males and females. Looking at the maps in detail, there was a geographical variation even within the southern provinces. The areas around large rivers, some costal areas, and costal islands showed a high mortality rate. Even in the middle and northern provinces, the eastern costal areas showed relatively higher mortality rates as compared to inland areas. Conversely, some southern areas known for low levels of pollution showed relatively lower mortality rates.This finding suggests a possible relationship between liver cancer and water-related foods from polluted rivers or seas. Further studies should be performed in order to clarify which factors cause this geographical variation.

Background: Helicobacter pylori are major carcinogen of gastric cancer, but the associations among gastric cancer, H. pylori infection status, and alcohol consumption are not fully described. This study aimed to clarify how H. pylori infection status affects the association between alcohol consumption and gastric cancer risk. Methods: We selected 949 case–cohort participants from the 18 863 Korean Multi-center Cancer Cohort (KMCC) populations. Gastric cancer incidence inside and outside of the subcohort were 12 and 254 cases, respectively. Seropositivities for CagA, VacA, and H. pylori infection were determined by performing immunoblot assays. Weighted Cox regression models were used to calculate hazard ratios and 95% confidence intervals (CIs). Results: Relative to non-drinking, heavy drinking (X7 times a week), and binge drinking (X55 g alcohol intake per occasion) showed a 3.48-fold (95% CI, 1.13–10.73) and 3.27-fold (95% CI, 1.01–10.56) higher risk in subjects not previously infected by H. pylori. There was no significant association between drinking pattern and gastric cancer risk in H. pylori IgG seropositive subjects. An increased risk for gastric cancer in heavy- and binge-drinking subjects were also present in subjects not infected by CagA- or VacA-secreting H. pylori. Conclusions: Heavy and binge alcohol consumption is an important risk factor related to an increasing incidence of gastric cancer in a population not infected by H. pylori.

Background Prostate cancer incidence and mortality rates in South Korea are relatively low, but rising steadily. Methods We examined age-standardized incidence and mortality trends of prostate cancer in South Korea to gain further insight into prostate cancer etiology. Results Although prostate cancer incidence has been low (7.9 per 100,000 man-years), it has increased up to 28.2% between 1996–1998 and 1999–2001. Prostate cancer mortality increased 12.7-fold over a 20-year period. Despite the increase in prostate cancer incidence and mortality rates, marked differences in rates remain for Koreans, Korean Americans, and Caucasian Americans. Conclusions The rising rates of prostate cancer in South Korea cannot be attributed entirely to PSA screening due to the low PSA screening prevalence; this trend is most likely related to increased westernization among Koreans. Interdisciplinary epidemiological studies incorporating the collection of biological samples are needed to clarify the extent to which lifestyle and genetic factors contribute to the observed racial disparity. Prostate. Published 2006 Wiley-Liss, Inc.

An inverse relationship between age and human papillomavirus (HPV) prevalence has been reported in many developed countries, but information on this relationship is scarce in many other parts of the world. We carried out a cross-sectional study of sexually active women from the general population of 15 areas in 4 continents. Similar standardised protocols for women's enrolment, cervical specimen collection and PCR-based assays for HPV testing were used. HPV prevalence in different age groups was compared by study area. 18,498 women aged 15-74 years were included. Age-standardised HPV prevalence varied more than 10-fold between populations, as did the shape of age-specific curves. HPV prevalence peaked below age 25 or 35, and declined with age in Italy, the Netherlands, Spain, Argentina, Korea and in Lampang, Thailand and Ho Chi Minh, Vietnam. This was not the case in Songkla, Thailand nor Hanoi, Vietnam, where HPV prevalence was low in all age groups. In Chile, Colombia and Mexico, a second peak of HPV prevalence was detected among older women. In the poorest study areas in Asia (Shanxi, China and Dindigul, India), and in Nigeria, HPV prevalence was high across all age groups. The substantial differences observed in age-specific curves of HPV prevalence between populations may have a variety of explanations. These differences, however, underline that great caution should be used in inferring the natural history of HPV from age-specific prevalences.

A considerable number of infectious agents have been classified as human carcinogens Group 1 by the International Agency for Research on Cancer. Major infection-related cancers such as cancers of nasopharynx (53%), stomach (60%) and liver (63%) occur in the World Health Organization Western Pacific Region. Many infection-related cancers are preventable, particularly those associated with human papilloma virus, Helicobacter pylori, human immunodeficiency virus-I, hepatitis B virus and hepatitis C virus and liver flukes. Mongolia shows the highest prevalence of hepatitis B virus and hepatitis C virus, and China shows the highest prevalence of Helicobacter pylori. Chronic infection is attributable for 17-28% of overall cancer incidence or mortality in China, Japan and Korea. Through infant immunization for hepatitis B, 30 of 37 countries and areas in the Western Pacific Region have reached the 2012 milestone of chronic hepatitis B virus infection prevalence of

To investigate the prevalence of and the risk factors for human papillomavirus (HPV) infection in South Korea, we interviewed and examined a randomly selected sample of 863 sexually active women (age range = 20–74 years, median 44) and 103 self-reported virgins from Busan. The presence of DNA of 34 different HPV types in cervical exfoliated cells was tested among sexually active women by means of a PCR-based assay. IgG antibodies against L1 virus-like particles (anti-VLPs) of HPV types 16, 18, 31, 33 and 58 were also evaluated by means of ELISA. The overall prevalence of HPV DNA was 10.4% (95% confidence interval, CI: 8.5–12.7%). The most often found HPV DNA types were HPV 70, HPV 16 and HPV 33; 19.8% (95% CI: 17.2–22.0) of sexually active women had antibodies against one or more HPV types. The most common anti-VLPs were against HPV 18, 31 and 16. Prevalences standardized by age on the basis of the world standard population were 13.0% for HPV DNA and 17.1% for anti-VLPs. The concordance between the 2 HPV markers at an individual level was modest, but the risk factors for detection of HPV DNA and anti-VLPs were similar: number of lifetime sexual partners (odds ratio, OR for ≥ 4 vs. 1 = 3.5 and 5.4, respectively), seropositivity for herpes simplex virus-2 antibodies (OR = 2.6 and 2.5, respectively) and being single or divorced. HPV DNA, but not anti-VLPs, were elevated among women whose husbands were thought by their wives to have extra-marital affairs and those who had undergone vasectomy. Among 103 virgins, 4.9% had anti-VLPs (1/73 among those aged 24 years or less). © 2002 Wiley-Liss, Inc.

Purpose: To produce the nationwide 5-year survival rates of Korean cancer patients by primary cancer site. Materials and Methods: The study subjects were cancer patients diagnosed in 1995, as documented by the Korea Central Cancer Registry (KCCR) Program. This data was collected in 120 (93%) of 129 nationwide intern-and resident-training hospitals and 75 (94%) of the 80 Korean university hospitals. Follow-up was performed by obtaining information upon vital status (i.e., whether living or dead) from the government administered whole population files. Cumulative observed survival rate (OSR) was calculated by using the life table method and the relative survival rate (RSR) was computed using the life-time table for the years 1995, 1997, and 1999. Results: Of the 55,042 study subjects, the OSR for all Korean cancer patients was 61.4% at 1 year and 38.1% at 5 years. The RSR for all cancers was 62.5% at 1 year and 41.4% at 5 years, and the 5-year RSRs for all cancers in men and women were 32.6% and 53.2%, respectively. Conclusion: This is the first nationwide report upon 5-year cancer survival by primary site in Korea. Men showed a lower survival rate than women in most malignancies. Pancreatic and thyroid cancer had the lowest and highest 5-year survival rates, respectively.

1932-6203 Park, Sohee Kim, Yeonju Shin, Hai-Rim Lee, Boram Shin, Aesun Jung, Kyu-Won Jee, Sun Ha Kim, Dong Hyun Yun, Young Ho Park, Sue Kyung Boniol, Mathieu Boffetta, Paolo Journal Article United States PLoS One. 2014 Apr 10;9(4):e90871. doi: 10.1371/journal.pone.0090871. eCollection 2014.; International audience; BACKGROUND: Changes in lifestyle including obesity epidemic and reduced physical activity influenced greatly to increase the cancer burden in Korea. The purpose of the current study was to perform a systematic assessment of cancers attributable to obesity and physical inactivity in Korea. METHODOLOGY/PRINCIPAL FINDINGS: Gender- and cancer site-specific population-attributable fractions (PAF) were estimated using the prevalence of overweight and obesity in 1992-1995 from a large-scale prospective cohort study, the prevalence of low physical activity in 1989 from a Korean National Health Examination Survey, and pooled relative risk estimates from Korean epidemiological studies. The overall PAF was then estimated using 2009 national cancer incidence data from the Korea Central Cancer Registry. Excess body weight was responsible for 1,444 (1.5%) and 2,004 (2.2%) cancer cases among men and women, respectively, in 2009 in Korea. Among men, 6.8% of colorectal, 2.9% of pancreatic, and 16.0% of kidney cancer was attributable to excess body weight. In women, 6.6% of colorectal, 3.9% of pancreatic, 18.7% of kidney, 8.2% of postmenopausal breast, and 32.7% of endometrial cancer was attributable to excess body weight. Low leisure-time physical activity accounted for 8.8% of breast cancer, whereas the PAF for overall cancer was low (0.1% in men, 1.4% in women). Projections suggest that cancers attributable to obesity will increase by 40% in men and 16% in women by 2020. CONCLUSIONS/SIGNIFICANCE: With a significantly increasing overweight and physically inactive population, and increasing incidence of breast and colorectal cancers, Korea faces a large cancer burden attributable to these risk factors. Had the obese population of Korea remained stable, a large portion of obesity-related cancers could have been avoided. Efficient cancer prevention programs that aim to reduce obesity- and physical inactivity-related health problems are essential in Korea.

Objective: We have reviewed the potential cancer-preventive and other relevant properties of Panax ginseng C. A. Meyer, which has been traditionally used as a natural tonic in Oriental countries. Data identification and study selection: Publications on Panax ginseng and its relation to cancer were obtained from the Medline database (1983–1998) and by checking reference lists to find earlier reports. The reports cover experimental models and human studies on cancer-preventive activity, carcinogenicity and other beneficial or adverse effects. In addition, possible mechanisms of chemoprevention by ginseng were considered. Results: Published results from a cohort and two case–control studies in Korea suggest that the intake of ginseng may reduce the risk of several types of cancer. When ginseng was tested in animal models, a reduction in cancer incidence and multiplicity at various sites was noted. Panax ginseng and its chemical constituents have been tested for their inhibiting effect on putative carcinogenesis mechanisms (e.g., cell proliferation and apoptosis, immunosurveillance, angiogenesis); in most experiments inhibitory effects were found. Conclusion: While Panax ginseng C. A. Meyer has shown cancer-preventive effects both in experimental models and in epidemiological studies, the evidence is currently not conclusive as to its cancer-preventive activity in humans. The available evidence warrants further research into the possible role of ginseng in the prevention of human cancer and carcinogenesis.

Background In the Republic of Korea, cancer is the most common cause of death, and cancer incidence and mortality rates are the highest in East Asia. As alcoholic beverages are carcinogenic to humans, we estimated the burden of cancer related to alcohol consumption in the Korean population. Methods The cancer sites studied were those for which there is convincing evidence of a positive association with alcohol consumption: oral cavity, pharynx, esophagus, colon, rectum, liver, larynx and female breast. Sex- and cancer-specific population attributable fractions (PAF) were calculated based on: 1) the prevalence of alcohol drinkers among adults ≥20 years of age in 1989; 2) the average daily alcohol consumption (g/day) among drinkers in 1998; 3) relative risk (RR) estimates for the association between alcohol consumption and site-specific cancer incidence obtained either from a large Korean cohort study or, when more than one Korean study was available for a specific cancer site, meta-analyses were performed and the resulting meta-RRs were used; 4) national cancer incidence and mortality data from 2009. Results Among men, 3% (2,866 cases) of incident cancer cases and 2.8% (1,234 deaths) of cancer deaths were attributable to alcohol consumption. Among women, 0.5% (464 cancer cases) of incident cancers and 0.1% (32 deaths) of cancer deaths were attributable to alcohol consumption. In particular, the PAF for alcohol consumption in relation to oral cavity cancer incidence among Korean men was 29.3%, and the PAFs for pharyngeal and laryngeal cancer incidence were 43.3% and 25.8%, respectively. Among Korean women, the PAF for colorectal cancer incidence was the highest (4.2%) and that for breast cancer incidence was only 0.2%. Avoiding alcohol consumption, or reducing it from the median of the highest 4th quartile of consumption (56.0 g/day for men, 28.0 g/day for women) to the median of the lowest quartile (2.80 g/day for men, 0.80 g/day for women), would reduce the burden of alcohol-related cancers in Korea. Conclusions A reduction in alcohol consumption would decrease the cancer burden and a significant impact is anticipated specifically for the cancers oral cavity, pharynx, and larynx among men in the Republic of Korea.

Aim This work describes the human papillomavirus (HPV) prevalence and the HPV type distribution in a large series of vaginal intraepithelial neoplasia (VAIN) grades 2/3 and vaginal cancer worldwide. Methods We analysed 189 VAIN 2/3 and 408 invasive vaginal cancer cases collected from 31 countries from 1986 to 2011. After histopathological evaluation of sectioned formalin-fixed paraffin-embedded samples, HPV DNA detection and typing was performed using the SPF-10/DNA enzyme immunoassay (DEIA)/LiPA25 system (version 1). A subset of 146 vaginal cancers was tested for p16INK4a expression, a cellular surrogate marker for HPV transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance. Results HPV DNA was detected in 74% (95% confidence interval (CI): 70–78%) of invasive cancers and in 96% (95% CI: 92–98%) of VAIN 2/3. Among cancers, the highest detection rates were observed in warty-basaloid subtype of squamous cell carcinomas, and in younger ages. Concerning the type-specific distribution, HPV16 was the most frequently type detected in both precancerous and cancerous lesions (59%). p16INK4a overexpression was found in 87% of HPV DNA positive vaginal cancer cases. Conclusions HPV was identified in a large proportion of invasive vaginal cancers and in almost all VAIN 2/3. HPV16 was the most common type detected. A large impact in the reduction of the burden of vaginal neoplastic lesions is expected among vaccinated cohorts.

In a nested case–control study of 86 cases of gastric adenocarcinoma in relation to Helicobactor pylori infection in the Korean Multi-center Cancer Cohort, the H. pylori IgG seropositivity was 83.7% and that of the 344 matched controls was 80.8%, with a matched odds ratio for H. pylori infection of 1.06 (95% CI, 0.80–1.40).

Contribution over time of human papillomavirus (HPV) types in human cancers has been poorly documented. Such data is fundamental to measure current HPV vaccines impact in the years to come. We estimated the HPV type-specific distribution in a large international series of invasive cervical cancer (ICC) over 70 years prior to vaccination. Paraffin embedded ICC cases diagnosed between 1940 and 2007 were retrieved from eleven countries in Central-South America, Asia and Europe. Included countries reported to have low-medium cervical cancer screening uptake. Information on age at and year of diagnosis was collected from medical records. After histological confirmation, HPV DNA detection was performed by SPF-10/DEIA/LiPA25 (version1). Logistic regression models were used for estimating the adjusted relative contributions (RC) of HPV16 and of HPV18 over time. Among 4,771 HPV DNA positive ICC cases, HPV16 and HPV18 were the two most common HPVs in all the decades with no statistically significant variations of their adjusted-RC from 1940–59 to 2000–07 (HPV16—from 61.5 to 62.1%, and HPV18—from 6.9 to 7.2%). As well, the RC of other HPV types did not varied over time. In the stratified analysis by histology, HPV16 adjusted-RC significantly increased across decades in adenocarcinomas. Regarding age, cases associated to either HPV16, 18 or 45 were younger than those with other HPV types in all the evaluated decades. The observed stability on the HPV type distribution predicts a high and stable impact of HPV vaccination in reducing the cervical cancer burden in future vaccinated generations.

Objectives: To examine the association between body mass index (BMI), physical activity and colorectal cancer risk among Korean adults. Methods: Data from the Korean Multi-center Cancer Cohort (KMCC) between 1993 and 2005 were analyzed. The study population comprised 12,379 subjects aged above 20 years old. The subjects were followed until December 31, 2011 (median follow-up of 10.1 years). Measured weight and height values was used to calculate BMI and self-reported total time spent for physical activity were used. The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of BMI and physical activity for colorectal cancer risk. Results: Men who did moderate physical activity showed a lower risk for colorectal cancer (HR 0.35, 95% CI: 0.19-0.65 for 30-419 minutes compared to who spend less than 30 minutes a week doing moderate activities). We did not find any association between the total time of vigorous activities and muscle-strengthening activities and colorectal cancer risk in both men and women. Men with BMI of 25 or higher showed an increased risk for colorectal cancer compared to men with BMI of 18.5 to 22.9 (HR 1.64, 95% CI 0.94-2.88 for 25.0-29.9 kg/m2; HR 1.64, 95% CI 0.94-2.88 for greater than 30.0 kg/m2). Conclusions: Moderate physical activities were associated with lower colorectal cancer risk among Korean men. Citation Format: Sooyoung Cho, Aesun Shin, Sue K. Park, Hai-Rim Shin, Soung-Hoon Chang, Keun-Young Yoo. Body mass index, physical activity and risk of colorectal cancer in the Korean Multi-center Cancer Cohort (KMCC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1734.

Background There has been limited study on the effect of infection with different hepatitis C virus (HCV) genotypes on the risk of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) endemic regions of Asia. Methods Hazard ratios of HCC development were estimated for HBV and HCV co-infected subjects among a community-based prospective cohort. HCV genotype was determined in HCV RNA-positive samples. Incident HCC cases were identified through linkage to the cancer registry. Results HCC incidence was 79 per 100,000 person-years in the study population (50 incident cases among 6,694 individuals within 63,170 person-years with an average of 9.4 years of follow-up); seroprevalence of HBsAg and anti-HCV was 5.2% and 5.6%. Adjusted hazard ratios of HCC by HBsAg positivity and anti-HCV positivity were 13.3 (CI: 7.3-24.4) and 6.7 (CI: 3.6-12.6). HRs of HBV and HCV monoinfection, and HBV/HCV coinfection were 17.1 (CI: 8.4-34.8), 10.4 (CI: 4.9-22.1) and 115.0 (CI: 32.5-407.3). Multiplicative synergistic effect of HBV/HCV coinfection on HCC risk was also observed (synergy index: 4.5, CI: 1.3-15.5). Infection with HCV genotype 1 (HR: 29.7, CI: 13.6-46.8) and mixed infection with genotype 1 and 2 (HR: 68.7, CI: 16.4-288.4) significantly elevated HCC risk, much higher than HBV infection. Conclusions The effect of differences in HCV genotype and the multiplicative synergistic effect of HBV/HCV coinfection on HCC risk shown in the present study underline the need for comprehensive identification of hepatitis infection status in order to prevent and control HCC in this HBV endemic area.

The study aimed to examine the association between genes encoding molecules in the ornithine decarboxylase (ODC)-polyamine pathway (ODC1, AMD1, NQO1, NOS2A, and OAZ2) and gastric cancer risk and whether the gene-phytoestrogen interaction modifies gastric cancer risk.Among 76 gastric cancer cases and their 1:4 matched controls within the Korean Multi-center Cancer Cohort, a total of 30 SNPs in five genes involved in the ODC pathway were primarily analyzed. The second-stage genotyping in 388 matched case-control sets was conducted to reevaluate the significant SNPs interacting with phytoestrogens during the primary analysis. The summary odds ratios (ORs) [95 % confidence intervals (CIs)] for gastric cancer were estimated. Interaction effects between the SNPs and plasma concentrations of phytoestrogens (genistein, daidzein, equol, and enterolactone) were evaluated.In the pooled analysis, NQO1 rs1800566 showed significant genetic effects on gastric cancer without heterogeneity [OR 0.83 (95 % CI 0.70-0.995)] and a greater decreased risk at high genistein/daidzein levels [OR 0.36 (95 % CI 0.15-0.90) and OR 0.26 (95 % CI 0.10-0.64), respectively; p interaction 0.05]. Risk alleles of AMD1 rs1279599, AMD1 rs7768897, and OAZ2 rs7403751 had a significant gene-phytoestrogen (genistein and daidzein) interaction effect to modify the development of gastric cancer. They had an increased gastric cancer risk at low isoflavone levels, but a decreased risk at high isoflavone levels (p interaction 0.01).Our findings suggest that common variants in the genes involved in the ODC pathway may contribute to the risk of gastric cancer possibly by modulating ODC polyamine biosynthesis or by interaction between isoflavones and NQO1, OAZ2, and AMD1.

Cancer is becoming an increasingly important health problem in the low- and middle-income countries in the Asia Pacific region, as well as in high-income countries because of ageing populations and changes in lifestyle associated with economic development and epidemiologic transition. This paper reviews the cancer burden and control in the Asia Pacific region (limited to East Asia, South Eastern Asia and Pacific Islands countries, territories and other areas), with relevant information primarily extracted from the GLOBOCAN 2008, Cancer Incidence in Five Continents series and WHO websites. Most low- and middle-income countries have a cancer control strategy and/or an action plan; however, coverage of cancer registration is still very low and does not meet the international standard in terms of quality. Therefore, only limited data were available for the recent global estimation of cancer burden. Large variations, in both cancer incidence and mortality, were observed in the populations in the different sub-regions of Asia. The most common cancer in males is lung cancer in the Eastern and South Eastern sub-regions, while prostate cancer comes close to lung cancer in the Pacific Island countries. In females, breast cancer is the most common in all three regions. The predominance of lung, stomach, colorectal, prostate, breast and cervical cancers makes cancer control more amenable in the Asia Pacific region. Up-to-date statistics on cancer occurrence and outcome are essential for the planning and evaluation of cancer control programmes. Priority can be given to population-based cancer registration, risk reduction, especially tobacco control, and primary health care based enhancement of health care systems to diagnose and manage cancer specifically in low- and middle-income countries.

OBJECTIVES: To evaluate whether genes that encode CagA-interacting molecules (SRC, PTPN11, CRK, CRKL, CSK, c-MET and GRB2) are associated with gastric cancer risk and whether an interaction between these genes and phytoestrogens modify gastric cancer risk. METHODS: In the discovery phase, 137 candidate SNPs in seven genes were analyzed in 76 incident gastric cancer cases and 322 matched controls from the Korean Multi-Center Cancer Cohort. Five significant SNPs in three genes (SRC, c-MET and CRK) were re-evaluated in 386 cases and 348 controls in the extension phase. Odds ratios (ORs) for gastric cancer risk were estimated adjusted for age, smoking, H. pylori seropositivity and CagA strain positivity. Summarized ORs in the total study population (462 cases and 670 controls) were presented using pooled- and meta-analysis. Plasma concentrations of phytoestrogens (genistein, daidzein, equol and enterolactone) were measured using the time-resolved fluoroimmunoassay. RESULTS: SRC rs6122566, rs6124914, c-MET rs41739, and CRK rs7208768 showed significant genetic effects for gastric cancer in both the pooled and meta-analysis without heterogeneity (pooled OR = 3.96 [95% CI 2.05-7.65], 1.24 [95% CI = 1.01-1.53], 1.19 [95% CI = 1.01-1.41], and 1.37 [95% CI = 1.15-1.62], respectively; meta OR = 4.59 [95% CI 2.74-7.70], 1.36 [95% CI = 1.09-1.70], 1.20 [95% CI = 1.00-1.44], and 1.32 [95% CI = 1.10-1.57], respectively). Risk allele of CRK rs7208768 had a significantly increased risk for gastric cancer at low phytoestrogen levels (p interaction

Estimates of the worldwide incidence and mortality from 27 cancers in 2008 have been prepared for 182 countries as part of the GLOBOCAN series published by the International Agency for Research on Cancer. In this article, we present the results for 20 world regions, summarizing the global patterns for the eight most common cancers. Overall, an estimated 12.7 million new cancer cases and 7.6 million cancer deaths occur in 2008, with 56% of new cancer cases and 63% of the cancer deaths occurring in the less developed regions of the world. The most commonly diagnosed cancers worldwide are lung (1.61 million, 12.7% of the total), breast (1.38 million, 10.9%) and colorectal cancers (1.23 million, 9.7%). The most common causes of cancer death are lung cancer (1.38 million, 18.2% of the total), stomach cancer (738,000 deaths, 9.7%) and liver cancer (696,000 deaths, 9.2%). Cancer is neither rare anywhere in the world, nor mainly confined to high-resource countries. Striking differences in the patterns of cancer from region to region are observed.

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

Background: A number of infectious agents have been classified as human carcinogens. The purpose of the current study was to provide an evidence-based assessment of the burden of infection-related cancers in the Korean population. Materials and methods: The population attributable fraction was calculated using infection prevalence data from 1990 or earlier, relative risk estimates from meta-analyses using mainly Korean studies and national data on cancer incidence and mortality for the year 2007. Results: The fractions of all cancers attributable to infection were 25.1% and 16.8% for cancer incidence in men and women, and 25.8% and 22.7% of cancer mortality in men and women, respectively. Among infection-related cancers, Helicobacter pylori was responsible for 56.5% of cases and 45.1% of deaths, followed by hepatitis B virus (HBV) (23.9% of cases and 37.5% of deaths) and human papillomavirus (HPV) (11.3% of cases and 6% of deaths) and then by hepatitis C virus (HCV) (6% of cases and 9% of deaths). Over 97% of infection-related cancers were attributable to infection with H. pylori, HBV, HCV and HPV. Conclusion: Up to one-quarter of cancer cases and deaths would be preventable through appropriate control of infectious agents in Korea. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Summary Background Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. Methods Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. Findings 22 661 paraffin-embedded samples were obtained from 14 249 women. 10 575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90–92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70–72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92–96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6–50·4], 48·2 years [47·3–49·2], 46·8 years [46·6–48·1], and 55·5 years [54·9–56·1], respectively). Interpretation To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45. Funding Spanish grants from Instituto de Salud Carlos III, Agencia de Gestio d'Ajuts Universitaris i de Recerca, Marato de TV3 Foundation, and unrestricted grants from GlaxoSmithKline Biologicals, Sanofi Pasteur MSD, and Merck.

Cancer Information Section/Data Analysis and InterpretationGroup, International Agency for Research on Cancer, Lyon, France*For reprints and all correspondence: Ryo Konno, Department of Obstetrics and Gynecology, Jichi MedicalUniversity Saitama Medical Center, 1-847 Amanumacho, Ohmiya-ku, Saitama 330-8503, Japan.E-mail: kryo772007@yahoo.co.jpDisease burden of cervical cancer in Asia was summarized. Human papillomavirus 16 isthe most oncogenic human papillomavirus type. Korea’s national cervical cancer screeningprogram targets women aged 30 or over, with coverage of almost 80%. Japan has a longhistory (50 years) of cervical cancer screening, and cytological screening programs havereduced the incidence/mortality of cervical cancer by 70%. But, recent cervical cancerscreening coverage is 24%. Modeling suggested that vaccination of all 12-year-old girlswould reduce cervical cancer cases by 73% in Japan. India has no cervical cancer screen-ing program, as well as a serious lack of awareness in the general population, medicalprofessionals and policy-makers. A realistic, affordable approach would be a low-volume,once-in-a-lifetime human papillomavirus-based screening program. In Australia, the nationalcervical cancer program has been very successful in reducing the incidence and mortalityof cervical cancer. Australia was the first country to implement free, national humanpapillomavirus immunization (April 2007), expected to reduce human papillomavirus 16infections by 56% in 2010 and 92% in 2050. A comparison of the UK and Japan wasdemonstrated that in the UK, cervical cancer screening and human papillomavirus vacci-nation uptakes are high because the government provides adequate education/funding. TheJapanese government needs to put more emphasis on women’s health and preventativemedicine. Our conclusion and recommendations are that heightened public awarenessof cervical cancer prevention, focusing on screening and vaccination will lead to improvedsurvival and a better quality of life.Key words: cervical cancer – human papillomavirus – screening – vaccination – prevention

PURPOSE To estimate the number of cancer cases during 2002 in Korea through a nationwide hospital based cancer registration by the Korea Central Cancer Registry (KCCR). MATERIALS AND METHODS One hundred and thirty nine hospitals participated in the KCCR program in 2002. Cancer cases were coded and classified according to the International Classification of Diseases for Oncology 2(nd) edition (ICD-O-2). The software program "IARC Check" was used to evaluate the quality of registered cancer cases. Of the 122,770 malignancies registered, 11,732 (9.6%) duplicated malignancies were excluded. Among the remaining 102,677 malignancies, 3,652 (3.6%) cases with carcinoma in situ (Morphology code/2) were separated. Finally, 99,025 malignancies were analyzed. RESULTS Of the total of 99,025 malignancies, 55,398 (55.9%) cases were males and 43,627 (44.1%) were females. More than one third of cases were from the elderly (65 years old and more). The six leading primary cancer sites in the order of their relative frequency, were stomach (24.0%), followed by the lung (16.0%), the liver (15.4%), the colorectum (11.6%), the bladder (3.2%), and the prostate (3.0%) among males. In females, the breast (16.8%) was the common cancer site, followed by the stomach (15.3%), the colorectum (10.7%), the thyroid gland (9.5%), the cervix uteri (9.1%), and the lung (6.6%). CONCLUSION With the continued increase in cancer cases especially prostate cancer among males and thyroid cancer among females, the total number of registered cancer cases in Korea continues to rapidly increase.

PURPOSE To estimate the number of cancer cases during 2001, in Korea, through a nationwide hospital based cancer registration by the Korea Central Cancer Registry (KCCR). MATERIALS AND METHODS One hundred and thirty four hospitals participated in the KCCR program in 2001. Cancer cases were coded and classified according to the International Classification of Diseases for Oncology 2(nd) edition (ICD-O-2). The software program "IARC Check" was used to evaluate the quality of the registered cancer cases. Of the 111,816 malignancies registered, 10,106 (9.0%) duplicated malignancies were excluded. Among the remaining 95,542 malignancies, 3,598 (3.8%) cases with carcinoma in situ (Morphology code/2) were separated. Finally, 91,944 malignancies were analyzed. RESULTS Of the total 91,944 malignancies, 51,753 (56.3%) cases were males and 40,191 (43.7%) were females. More than one third of cases were from the elderly (65 years old and more). The six leading primary cancer sites, in the order of their relative frequency, were stomach (24.1%), followed by the lung (16.0%), the liver (16.0%), the colorectum (10.5%), the bladder (3.4%), and the prostate (2.8%) among males. In females, the breast (16.1%) was the common cancer site, followed by the stomach (15.3%), the colorectum (10.5%), the cervix uteri (10.1%), the thyroid gland (8.3%) and the lung (6.6%). CONCLUSION With the continued increase in cancer cases, the total number of registered cancer cases in Korea continues to rapidly increase.

Breast cancer risk is increasing in most Asian female populations, but little is known about the long-term mortality trend of the disease among these populations. We extracted data for Hong Kong (1979–2005), Japan (1963–2006), Korea (1985–2006), and Singapore (1963–2006) from the World Health Organization (WHO) mortality database and for Taiwan (1964–2007) from the Taiwan cancer registry. The annual age-standardized, truncated (to ≥20 years) breast cancer death rates for 11 age groups were estimated and joinpoint regression was applied to detect significant changes in breast cancer mortality. We also compared age-specific mortality rates for three calendar periods (1975–1984, 1985–1994, and 1995–2006). After 1990, breast cancer mortality tended to decrease slightly in Hong Kong and Singapore except for women aged 70+. In Taiwan and Japan, in contrast, breast cancer death rates increased throughout the entire study period. Before the 1990s, breast cancer death rates were almost the same in Taiwan and Japan; thereafter, up to 1996, they rose more steeply in Taiwan and then they began rising more rapidly in Japan than in Taiwan after 1996. The most rapid increases in breast cancer mortality, and for all age groups, were in Korea. Breast cancer mortality trends are expected to maintain the secular trend for the next decade mainly as the prevalence of risk factors changes and population ages in Japan, Korea, and Taiwan. Early detection and treatment improvement will continue to reduce the mortality rates in Hong Kong and Singapore as observed in Western countries. (Cancer Sci 2010; 101: 1141–1246)

Cholangiocarcinoma is relatively rare, but high incidence rates have been reported in Eastern Asia, especially in Thailand. The etiology of this cancer of the bile ducts appears to be mostly due to specific infectious agents. In 2009, infections with the liver flukes, Clonorchis sinensis or Opistorchis viverrini, were both classified as carcinogenic to humans by the International Agency for Research on Cancer for cholangiocarcinoma. In addition, a possible association between chronic infection with hepatitis B and C viruses and cholangiocarcinoma was also noted. The meta-analysis of published literature revealed the summary relative risks of infection with liver fluke (both Opistorchis viverrini and Clonorchis sinensis), hepatitis B virus, and hepatitis C virus to be 4.8 (95% confidence interval [95% CI]: 2.8-8.4), 2.6 (95% CI: 1.5-4.6), and 1.8 (95% CI: 1.4-2.4), respectively - liver fluke infection being the strongest risk factor for cholangiocarcinoma. Countries where human liver fluke infection is endemic include China, Korea, Vietnam, Laos, and Cambodia. The number of infected persons with Clonorchis sinensis in China has been estimated at 12.5 million with considerable variations among different regions. A significant regional variation in Opistorchis viverrini prevalence was also noted in Thailand (average 9.6% or 6 million people). The implementation of a more intensive preventive and therapeutic program for liver fluke infection may reduce incidence rates of cholangiocarcinoma in endemic areas. Recently, advances have been made in the diagnosis and management of cholangiocarcinoma. Although progress on cholangiocarcinoma prevention and treatment has been steady, more studies related to classification and risk factors will be helpful to develop an advanced strategy to cure and prevent cholangiocarcinoma.