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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 (

Background: Cancer has become a priority public health challenge in the Member States of the World Health Organization’s (WHO) Western Pacific Region (WPR). Rapid and unplanned urbanization, demographic transition, and lifestyle changes are driving the increase in noncommunicable diseases (NCDs), which include cancer. The WHO Global Action Plan for the Prevention and Control of Noncommunicable Diseases 2013-2020, targets a reduction in premature mortality from NCDs by 25% by 2025. Objectives: The aim of this study was to review the epidemiology of cancer including cancer controlefforts in the WPR. Methods: Information was primarily extracted from Globocan 2012, 'Cancer Incidence in Five Continents Vol. X', and the NCD country capacity survey carried out by the WHO in 2013. The WPR, with one-fourth of the world’s population, has one-third of all cancers globally. Cancer cases in the WPR are expected to increase from 4.5 million new cases in 2012 to 6.4 million in 2025. Findings: In most of the low- and middle-income countries (LMICs) in Asia and in Pacific Island countries and areas, coverage of cancer registration is relatively low and they face many challenges in quality of cancer registry data. Eighty-five percent of LMICs have indicated the existence of a cancer control policy strategy and/or action plan. The predominance of lung, stomach, colorectal, breast, and cervical cancers makes control of the disease more amenable in the WPR. A relatively high ratio of mortality to incidence in LMICs reflects health-system limitations, especially in the diagnosis and management of cancer. Conclusions: Strengthening cancer registration, tobacco control, and promotion of a healthy diet, as well as HBV and HPV vaccination, is the priority areas to reduce cancer burden. Health-system strengthening with a defined package of services at different levels, referral care, trained human resources, and appropriate technology is necessary to improve cancer management. Pain relief and palliative care are priorities as well. A well-planned national cancer control program with a strong component of surveillance and monitoring can help to reduce the cancer burden in LMICs and Pacific Island countries.

Objectives Emerging evidence indicates that sleep duration is associated with health outcomes. However, the relationship of sleep duration with long-term health is unclear. This study was designed to determine the relationship of sleep duration with mortality as a parameter for long-term health in a large prospective cohort study in Korea. Methods The study population included 13 164 participants aged over 20 years from the Korean Multi-center Cancer Cohort study. Information on sleep duration was obtained through a structured questionnaire interview. The hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were estimated using a Cox regression model. The non-linear relationship between sleep duration and mortality was examined non-parametrically using restricted cubic splines. Results The HRs for all-cause mortality showed a U-shape, with the lowest point at sleep duration of 7 to 8 hours. There was an increased risk of death among persons with sleep duration of ≤5 hours (HR, 1.21; 95% CI, 1.03 to 1.41) and of ≥10 hours (HR, 1.36; 95% CI, 1.07 to 1.72). In stratified analysis, this relationship of HR was seen in women and in participants aged ≥60 years. Risk of cardiovascular disease-specific mortality was associated with a sleep duration of ≤5 hours (HR, 1.40; 95% CI, 1.02 to 1.93). Risk of death from respiratory disease was associated with sleep duration at both extremes (≤5 and ≥10 hours). Conclusions Sleep durations of 7 to 8 hours may be recommended to the public for a general healthy lifestyle in Korea.

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.

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.

OBJECTIVES Diabetes and obesity each increases mortality, but recent papers have shown that lean Asian persons were at greater risk for mortality than were obese persons. The objective of this study is to determine whether an interaction exists between body mass index (BMI) and diabetes, which can modify the risk of death by cardiovascular disease (CVD). METHODS Subjects who were over 20 years of age, and who had information regarding BMI, past history of diabetes, and fasting blood glucose levels (n=16 048), were selected from the Korea Multi-center Cancer Cohort study participants. By 2008, a total of 1290 participants had died; 251 and 155 had died of CVD and stroke, respectively. The hazard for deaths was calculated with hazard ratio (HR) and 95% confidence interval (95% CI) by Cox proportional hazard model. RESULTS Compared with the normal population, patients with diabetes were at higher risk for CVD and stroke deaths (HR, 1.84; 95% CI, 1.33 to 2.56; HR, 1.82; 95% CI, 1.20 to 2.76; respectively). Relative to subjects with no diabetes and normal BMI (21 to 22.9 kg/m(2)), lean subjects with diabetes (BMI

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.

Objectives: To examine the association between alcohol consumption habit, types of beverages, alcohol consumption quantity, and overall and cancer-specific mortality among Korean adults. Methods: The alcohol consumption information of a total of 16 320 participants who were 20 years or older from the Korean Multicenter Cancer Cohort were analyzed to examine the association between alcohol consumption habit and mortality (median follow-up of 9.3 years). The Cox proportional hazard model was used to estimate the hazard ratio (HR) of alcohol consumption to mortality adjusting for age, sex, geographic areas, education, smoking status, and body mass index. Results: Alcohol drinkers showed an increased risk for total mortality compared with never drinkers (HR, 1.72; 95% confidence interval [CI], 1.38 to 2.14 for past drinkers; HR, 1.21; 95% CI, 1.06 to 1.39 for current drinkers), while past drinkers only were associated with higher risk for cancer deaths (HR, 1.84; 95% CI, 1.34 to 2.53). The quantity of alcohol consumed per week showed a J-shaped association with risk of mortality. Relative to light drinkers (0.01 to 90 g/wk), never drinkers and heavy drinkers (>504 g/wk) had an increased risk for all-cause and cancer deaths: (HR, 1.18; 95% CI, 0.96 to 1.45) and (HR, 1.39; 95% CI, 1.05 to 1.83) for all-cause mortality; and (HR, 1.55; 95% CI, 1.15 to 2.11) and (HR, 2.07; 95% CI, 1.39 to 3.09) for all cancer mortality, respectively. Heavy drinkers (>504 g/wk) showed an elevated risk for death from stomach and liver cancers. Conclusions: The present study supports the existence of a J-shaped association between alcohol consumption quantity and the risk of all-cause and cancer deaths. Heavy drinkers had an increased risk of death from cancer overall and liver and stomach cancer.

A successful approach to reducing the burden of non-communicable disease requires action at all stages of life, argue Bente Mikkelsen and colleagues

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.

Compared with the West, the overall incidence of lymphoid neoplasms is lower, and the subtype distribution is distinct in Asia. To comprehensively investigate the subtype distribution with the age and sex factors, and temporal changes of subtype proportions, we re-assessed all patients with lymphoid neoplasms diagnosed at a large oncology service in the Republic of Korea from 1989 to 2008 using the World Health Organization classifications. Of the total 5,318 patients, 66.9% had mature B-cell neoplasms, 12.5% had mature T/natural killer (NK)-cell neoplasms, 16.4% had precursor lymphoblastic leukemia/lymphoma (ALL/LBL), and 4.1% had Hodgkin's lymphoma. The most common subtypes were diffuse large B-cell lymphoma (30.5%), plasma cell myeloma (14.0%), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma; 12.4%), B-cell ALL/LBL (11.3%), Hodgkin's lymphoma (4.1%), peripheral T-cell lymphoma unspecified (4.0%), T-cell ALL/LBL (3.9%), and extranodal NK/T-cell lymphoma of nasal type (3.9%). Most subtypes showed male predominance, with an average M/F ratio of 1.3. Most mature lymphoid neoplasms were diseases of adults (mean age, 53.5 yr), whereas ALL/LBLs were of young individuals (mean age, 20.3 yr). When the relative proportion of subtypes were compared between two decades (1989-1998 vs. 1999-2008), especially MALT lymphoma has increased in proportion, whereas T/NK-cell neoplasms and ALL/LBL have slightly decreased. In summary, the lymphoid neoplasms of Koreans shared some epidemiologic features similar to those of other countries, whereas some subtypes showed distinct features. Although the increase in incidence of lymphoid neoplasms is relatively modest in Korea, recent increase of MALT lymphoma and decrease of T/NK-cell neoplasms and ALL/LBL are interesting findings.

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.

Background Dietary factors contribute to the risk of developing metabolic syndrome, a disorder associated with an increased risk of developing cardiovascular disease, diabetes mellitus, and some cancers. Objective The objective of this study was to evaluate the association between the intake frequencies of certain food groups, eating habits, and the risk of metabolic syndrome in a cross-sectional study of Korean men. Methods Study participants were recruited from the National Cancer Center in South Korea. A total of 7,081 men aged 30 years and older were recruited between August 2002 and May 2007. Metabolic syndrome was defined as having three or more of the following conditions: obesity, high blood pressure, low high-density lipoprotein cholesterol level, high triglyceride level, and high fasting blood glucose level. The association of metabolic syndrome and sociodemographic characteristics, food intake frequencies, and eating habits assessed by a food frequency questionnaire, was examined. Results The prevalence rate of metabolic syndrome for men aged 30 to 39, 40 to 49, 50 to 59, and 60+ years was 18.2%, 19.8%, 21.9%, and 20.5%, respectively. The study participants with metabolic syndrome had significantly higher family history of type 2 diabetes mellitus (27.6% vs 21.6%, P P =0.005) than their counterparts. Among food group items, participants with metabolic syndrome showed significantly higher intake of seaweed (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.05 to 1.50), and oily foods (OR 1.28, 95% CI 1.04 to 1.57) than participants without metabolic syndrome. In addition, the group with metabolic syndrome was more likely to eat quickly (OR 2.23, 95% CI 1.60 to 3.12 for fast vs slow) and to overeat frequently (OR 2.37, 95% CI 1.85 to 3.05 for more than 4 times a week vs less than once a week). Conclusions The results suggest that high intake of seaweed and oily foods as well as eating habits such as eating faster and frequent overeating, are associated with the risk of metabolic syndrome. In contrast, high fruit intake may be associated with a lower risk of metabolic syndrome. The importance of dietary habits in metabolic syndrome development needs to be pursued in further studies.

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.

Smoking increases the risk of squamous-cell carcinoma of the cervix but it is not clear whether smoking increases the risk of acquisition or persistence of human papillomavirus (HPV) infection. Information on smoking was collected from 10 areas in four continents among population-based age-stratified random samples of women aged 15 years or older. HPV testing was performed using PCR-based enzyme immunoassay. Unconditional logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) of being HPV-positive by smoking habits adjusted for age and lifetime number of sexual partners. Ten thousand five hundred and seventy-seven women (mean age 41.4 years) were included. Among current smokers the risk of being HPV-positive increased with smoking intensity after allowing for lifetime number of sexual partners: ORs for less than 5 5-14 and greater than or equal to 15 cigarettes per day were 1.21 (95% CI 0.95-1.54) 1.39 (95% CI 1.04-1.87) and 2.01 (95% CI 1.32-3.08) respectively as compared with never-smokers. The risk among former smokers (OR = 0.95 95% CI 0.73-1.23) was similar to that among never-smokers. Analyses stratified by lifetime number of sexual partners showed a significant trend in risk only for women with one lifetime sexual partner. Our study suggests that current though not former smoking is associated with an increased prevalence of HPV after allowance for sexual covariates. Among current smokers HPV prevalence increased with smoking intensity but a clear dose-response relationship was exclusively seen among women who declared one lifetime sexual partner. (authors)

Better information on the prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection is needed in many world areas.Cross-sectional study of population-based samples of nonpregnant women aged 15 to 44 years in Nigeria, Colombia, Argentina, Vietnam (2 areas), China, Thailand (2 areas), Korea, and Spain. 5,328 consenting women aged 15 to 44 years participated. Exfoliated cervical cells were collected and testing for CT and NG and human papillomavirus (HPV) was done using PCR-based assays.Age-standardized CT prevalence ranged between 0.2% (95% confidence interval, CI: 0.0-0.7%) in Spain and 5.6% (95% CI: 3.4-7.8%) in Nigeria. NG ranged between 0% (with broad CIs) in several areas and 2.6% (95% CI: 1.0-4.2%) in Nigeria. Prevalence of CT in all areas combined was greater in women aged 15 to 24 (4.5; 95% CI: 3.4-5.8%) than 25 to 44 (2.6; 95% CI: 2.1-3.1%), whereas NG prevalence was similar in the 2 age groups (0.3%). The only significant risk factors were NG infection (for CT), CT infection (for NG) and infection with high-risk HPV types (for both).The prevalence of CT and, most notably, NG was relatively low in a variety of countries. Our findings, however, do not apply to subsets of high-risk women who are likely to be underrepresented in our population-based samples.

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.

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.

To evaluate the prevalence and risk factors of Clonorchis sinensis infection, an epidemiologic survey was performed (3,169 residents; age range: 30-87 years; mean age = 59; 1,973 women) in three areas with different mortality rates of cholangiocarcinoma. C. sinensis prevalence was 2.1% in Chuncheon, 7.8% in Chungju, and 31.3% in Haman, where cholangiocarcinoma incidence rate was 0.3, 1.8, and 5.5 per 100,000 persons, respectively. Of the four major risk factors for C. sinensis (male sex, alcohol consumption, raw freshwater fish intake, and area of residence), area was the strongest. Efforts to discourage raw freshwater fish intake, treat egg carriers, and protect water sources from C. sinensis contamination should be strengthened in the Republic of Korea.

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.

Mortality due to liver cancer in Korea ranks as one of the highest in the world. Both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are high-risk factors for liver cancer. Although HBV is by far the more important risk factor for the development of hepatocellular carcinoma (HCC) in Korea, HCV infection is more closely associated with HCC in elderly patients. Therefore, the evaluation of risk factors for HCV infection, including blood transfusion, is important. This study reviews the literature on HCV prevalence and risk factors among the general population, as well as the distribution of HCV genotypes in Korea. An overall estimate of the prevalence of anti-HCV among Koreans older than 40 years was 1.29% (95% confidence interval 1.12–1.48) during 1995–2000. Blood transfusion was the strongest risk factor for transmission of HCV infection. Risk factors for HCV infection in Korea other than blood transfusion and history of acupuncture have not been proven. The most prevalent HCV genotype is 1b followed by 2a. Even though the prevalence of anti-HCV in Korea has been reduced and the risk of HCV transmission through blood transfusion has markedly decreased, public-health programs to prevent de novo infections should be developed. Moreover, most people infected with HCV in Korea are older than 40 years, and therefore, the surveillance of adults (≧40 years) for HCV infection will be helpful in early detection of HCC developing in them.

Summary Background The proportion of women infected with human papillomavirus (HPV) varies greatly across populations, as might the distribution of HPV types. We aimed to compare HPV-type distribution in representative samples of women from different world regions. Methods Women were randomly selected from the general population of 13 areas from 11 countries (Nigeria, India, Vietnam, Thailand, Korea, Colombia, Argentina, Chile, the Netherlands, Italy, and Spain). A standardised protocol was used for cervical specimen collection. All HPV testing was by GP5+/6+ PCR-based EIA. The proportion of HPV-positive women infected with different HPV types was compared by study area and between pooled regions with age-adjusted odds ratios (ORs) with corresponding 95% floating CIs. Findings 15 613 women aged 15–74 years without cytological abnormalities were included in a pooled analysis. Age-standardised HPV prevalence varied nearly 20 times between populations, from 1·4% (95% CI 0·5–2·2) in Spain to 25·6% (22·4–28·8) in Nigeria. Although both overall HPV prevalence and HPV16 prevalence were highest in sub-Saharan Africa, HPV-positive women in Europe were significantly more likely to be infected with HPV16 than were those in sub-Saharan Africa (OR 2·64, p=0·0002), and were significantly less likely to be infected with high-risk HPV types other than HPV16 (OR 0·57, p=0·004) and/or low-risk HPV types (OR 0·44. p=0·0002). Women from South America had HPV-type distribution in between those from sub-Saharan Africa and Europe. Heterogeneity between areas of Asia was significant. Interpretation Heterogeneity in HPV type distribution among women from different populations should be taken into account when developing screening tests for the virus and predicting the effect of vaccines on the incidence of infection.

Background. Little is known about the prevalence of human papillomavirus (HPV) infection in young adults in Asia. Methods. We invited female and male students in Busan, South Korea, to participate in a survey that included, for females, self-collection of vaginal cells and, for males, physician-performed collection of exfoliated genital cells. The prevalences of 25 HPV types were evaluated, by a polymerase chain reaction-based assay, in 672 female students (median age, 19 years) and in 381 male students (median age, 22 years). Results. HPV DNA was detected more frequently in female students (15.2%) than in male students (8.7%); in both sexes, high-risk HPV types were predominant. Among sexually active students, HPV prevalence was 38.8% in females and 10.6% in males. In female students, currently smoking cigarettes and having multiple lifetime sex partners were the strongest risk factors for HPV infection; in male students, associations between HPV prevalence and sexual habits were similar to those in female students but never attained statistical significance. Conclusions. Young women in South Korea start having penetrative sexual intercourse relatively late (median age, 18 years), but, once they begin, HPV prevalence quickly rises to levels comparable with those found in university students in the United States and in northern Europe. The high rate of participation in our study suggests that trials of new vaccines against HPV may be feasible among university students in South Korea.

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

Objectives To develop effective intervention programmes to control Clonorchis sinensis infection, three interventions were evaluated in a clonorchiasis-endemic area of Korea. Methods Four thousand two hundred and sixty-seven voluntary participants in Sancheong county were tested at baseline and two follow-up surveys after 1 and 3 years. Faecal samples were examined for C. sinensis eggs using the Kato-Katz method. Participants were divided into three intervention groups by areas and year recruited: national prevention programme only (mass health campaign and praziquantel treatment) for Group A; health education for community leaders added for Group B; and individual health education added for Group C. Results The prevalence of C. sinensis infection fell substantially in all three intervention groups between baseline and 3-year follow-up: from 31.1% to 14.9% in Group A, from 29.6% to 6.8% in Group B and from 21.9% to 8.6% in Group C. The control effectiveness was highest in Group B with 76.8%. The new infection rate was 16.3%, 12.8% and 7.6% in Group A, B and C, respectively. The reinfection rate was lower in Group B (3.8%) than Group C (12.2%). Conclusions To control C. sinensis infection in endemic areas of Korea, health education for community leaders or individuals on prevention of C. sinensis infection should be added to national control programmes. Objectifs Afin de developper des programmes d'intervention efficaces pour lutter contre l'infection par Clonorchis sinensis, trois interventions ont ete evaluees dans une zone endemique pour la clonorchiase en Coree. Methodes 4267 participants volontaires dans le comte de Sancheong ont ete testes a la base et au cours de deux enquetes de suivi apres 1 et 3 ans. Des echantillons fecaux ont ete examines pour les œufs de C. sinensis en utilisant la methode de Kato-Katz. Les participants ont ete divises en trois groupes d'intervention par zones et par annee de recrutement de la facon suivante; groupe A: uniquement le programme national de prevention (campagne sanitaire de masse et traitement au praziquantel), groupe B: education sanitaire en plus pour les leaders communautaires et groupe C: education sanitaire individuelle en plus. Resultats La prevalence de l'infection par C. sinensis a considerablement diminue dans tous les trois groupes d'intervention entre le niveau de reference et a 3 ans de suivi, en passant de 31,1% a 14,9% dans le groupe A, de 29,6% a 6,8% dans le groupe B et de 21,9% a 8,6% dans le groupe C. L'efficacite de la lutte etait la plus elevee dans le groupe B avec 76,8%. Le nouveau taux d'infection etait de 16,3%, 12,8% et 7,6% dans les groupes A, B et C, respectivement. Le taux de reinfection etait plus faible dans le groupe B (3,8%) que dans le groupe C (12,2%). Conclusions Pour lutter contre l'infection a C. sinensis dans les zones endemiques de la Coree, l’education sanitaire pour les leaders communautaires ou les individus en matiere de prevention de l'infection a C. sinensis devraient etre ajoutee aux programmes de lutte nationaux. Objetivos Con el fin de desarrollar programas de intervencion efectivos para controlar la infeccion por Clonorchis sinensis, se evaluaron tres intervenciones en un area endemica para clonorquiasis en Corea. Metodos A 4,267 participantes voluntarios del condado de Sancheong se les examino incorporarse al estudio y en dos ocasiones durante el seguimiento - tras 1 y 3 anos. Se examinaron muestras fecales en busca de huevos de C. sinensis utilizando el metodo de Kato-Katz. Los participantes se dividieron en tres grupos de intervencion por areas y ano en el que fueron reclutados: solo programa nacional de prevencion (campana masiva de salud y tratamiento con praziquantel) para el Grupo A; educacion sanitaria para lideres comunitarios anadido en el Grupo B; y educacion sanitaria individual anadida en el Grupo C. Resultados La prevalencia de infeccion por C. sinensis disminuyo de forma sustancial en los tres grupos de intervencion entre el inicio del estudio y tras los 3-anos de seguimiento: del 31.1% al 14.9% en el Grupo A, del 29.6% al 6.8% en el Grupo B, y del 21.9% al 8.6% en el Grupo C. La efectividad del control era mayor en el Grupo B con un 76.8%. La nueva tasa de infeccion era del 16.3%, 12.8% y 7.6% en el Grupo A, B y C, respectivamente. La tasa de reinfeccion era menor en el Grupo B (3.8%) que en el Grupo C (12.2%). Conclusiones Con el fin de controlar la infeccion por C. sinensis en areas endemicas de Corea, deberia de anadirse a los programas nacionales de control, el de educacion sanitaria de los lideres comunitarios en prevencion de la infeccion con C. sinensis.

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.

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).

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 chronic liver disease (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 analysed 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 (ROC) of 0.85 in distinguishing HCC from CLD in subjects with α-Fetoprotein (AFP) < 20 ng/mL. In a prospective cohort of 115 CLD patients from Korea, increased plasma levels of LTBP2 and/or OPN were detected in plasma collected over 2 years prior to diagnosis in 21 subjects who developed HCC. Thus, the combination of LTBP2 and OPN outperformed AFP for diagnosis and prediction of HCC and may therefore improve biomarker-based detection of HBV-related HCC.

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.

We investigated the independent and combined effects of alcohol consumption, cigarette smoking and metabolic syndrome on abnormal liver function, i.e., the elevation of serum liver enzyme levels. Participants of a Korean population-based prospective cohort aged ≥30 years without liver disease, diabetes, or cardiovascular diseases were included. Information on alcohol consumption, smoking status, and metabolic syndrome, defined as per the criteria of the Adult Treatment Panel III, were applied to evaluate their impact on serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Alcohol consumption, cigarette smoking and metabolic syndrome were the significant individual factors that elevated serum liver enzyme levels. Supra-additive effects of metabolic syndrome and either alcohol consumption or cigarette smoking were also identified. The combination of heavy drinking (≥24 g/day) and metabolic syndrome conferred an effect that was higher than the sum of the two individual effects (Synergic Index (SI): AST, 2.37 [1.20-4.67]; GGT, 1.91 [1.17-3.13]). Only GGT level (odds ratio 6.04 [3.68-9.94], SI 2.33 [1.24-4.41]) was significantly elevated when the effect of moderate drinking (20 pack years, 1.80 for ≥24 g/day and ≤20 pack years, 2.03 for ≥24 g/day and >20 pack years, while only the combined effect of drinking ≥24 g/day and smoking >20 pack years elevated the AST level (SI 4.55 [3.12-6.61]). The combined effect of cigarette smoking and metabolic syndrome was not supra-additive. To prevent fatty liver disease and other related diseases, a multifactorial prevention strategy that includes limited alcohol consumption, smoking cessation and rectification of adverse metabolic profiles is required.

Aims To identify, by laser capture microdissection (LCM), the cellular localization of HPV11 when present with carcinogenic HPV in invasive cervical cancer (ICC) specimens, and to relate this to p16(INK) (4a) expression. Methods and results Three squamous cell ICC specimens showing coinfection with HPV11 and carcinogenic HPV16 or HPV31 were selected from the Institut Catala d'Oncologia international survey of anogenital carcinomas, and coinfection was confirmed by SPF10 -DEIA-LiPA25 analysis. In two cases LCM-PCR identified HPV11 in low-grade and high-grade squamous intraepithelial lesions (SILs) adjacent to the ICC, and HPV16 or HPV31 in the ICC. In one case, HPV11 was the only genotype found in the ICC. P16(INK) (4a) expression was diffuse in ICC associated with carcinogenic HPV, but focal in ICC with HPV11. Conclusions Our results confirm that a single cervical, cancerous or precancerous lesion is associated with a single HPV type. Detecting low-risk HPV as a coinfection in whole tissue from ICC does not prove a causal association. HPV11 may be found only in an adjacent SIL with carcinogenic HPV in the ICC. It is also found alone in carcinoma. LCM-PCR and differential P16(INK) (4a) expression can clarify the causal role of each type when multiple HPVs are present in whole tissue from carcinomas.

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.

The goals of cancer control strategies are generally uniform across all constituencies and are to reduce cancer incidence, reduce cancer mortality, and improve quality of life for those affected by cancer. A well-constructed strategy will ensure that all of its elements can ultimately be connected to one of these goals. When a cancer control strategy is being implemented, it is essential to map progress towards these goals; without mapping progress, it is impossible to assess which components of the strategy require more attention or resources and which are not having the desired effect and need to be re-evaluated. In order to monitor and evaluate these strategies, systems need to be put in place to collect data and the appropriate indicators of performance need to be identified. Session 2 of the 4th International Cancer Control Congress (ICCC-4) focused on how to manage population health to prevent and detect cancers and non-communicable diseases through two plenary presentations and four interactive workshop discussions: 1) registries, measurement, and management in cancer control; 2) use of information for planning and evaluating screening and early detection programs; 3) alternative models for promoting community health, integrated care and illness management; and 4) control of non-communicable diseases. Workshop discussions highlighted that population based cancer registries are fundamental to understanding the cancer burden within a country. However, many countries in Africa, Asia, and South/ Central America do not have them in place. A new global initiative is underway, which brings together several international agencies, and aims to establish six IARC regional registration resource centres over the next five years. These will provide training, support, infrastructure and advocacy to local networks of cancer registries, and, it is hoped, improve the host countries' ability to assess and act on cancer issues within their jurisdictions. Multiple methods of programme evaluation were presented across workshops, but all were attuned to both the resource base and the specific questions to be addressed. Where innovative strategies were being tested, customized evaluation strategies should be undertaken. Where programmes are well-developed and data is being collected for evaluation, there is the opportunity for sophisticated analytical methods to be used to pinpoint specific areas or delivery sites for future quality improvement. Finally, unique opportunities now exist to integrate the strategies developed in cancer control and evaluation with those under development for other non-communicable diseases. This area will likely be one for future development.

Scope To investigate whether genes involved in AKT/nuclear factor kappa B signaling and/or gene–environment interactions between the genes and phytoestrogens may be susceptible factors for gastric cancer. Methods and results The representative single nucleotide polymorphisms (SNPs) identified during the primary analysis (screening a total of 622 SNPs within ± 5 kbp of the 51 target gene locations) were further investigated in 317 matched case–control sets. The summary odds ratios (ORs) and 95% confidence intervals (CIs) for gastric cancer were calculated. Interaction effects between the SNPs and phytoestrogen biomarkers (genistein, daidzein, equol, and enterolactone) were computed. CDK1 rs4145643, FAS rs6586161, and FAS rs1468063 in the AKT signaling pathway presented significant genetic effects on gastric cancer (OR = 0.81 (95% CI: 0.66–0.99) for CDK1 rs4145643; OR = 1.27 (95% CI: 1.03–1.58) for FAS rs6586161; OR = 1.29 (95% CI: 1.03–1.56) for FAS rs1468063; Cochran Q statistics > 0.10). Risk alleles of FAS rs6586161, FAS rs1468063, MAP3K1 rs16886448, and MAP3K1 rs252902 showed significant interaction effects with enterolactone (pinteraction < 0.05). Conclusion CDK1 and FAS genes involved in AKT signaling and influenced by anti-carcinogenic property of phytoestrogens can play a role as susceptible genetic factors in gastric carcinogenesis. FAS and MAP3K1 genes significantly interact with enterolactone, thereby modifying the individual's risk for gastric cancer.

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