Aetiology of cancer in Asia.

Cancer has become the leading cause of death in many Asian countries. There is an increasing trend in breast, prostate and colon cancers, which are considered as typical of economically developed countries. Although breast and prostate cancer rates are still lower than in western countries, they are particularly rapidly increasing. In this paper, we review recently published literature to identify important etiologic factors affecting the cancer risk in Asian populations. Infectious agents such as Helicobacter pylori, hepatitis B and C viruses, and human papillomavirus were shown to be associated with elevated risks of stomach, liver and cervical cancer, respectively. Tobacco smoking was shown to be significantly associated with higher lung cancer risk and moderately increased all cancer risk. Excessive alcohol drinking appeared to increase the risk of colorectal cancer in Japanese and breast cancer in the Korean population. Betel nut chewing was associated with higher risk of oral and esophageal cancer. In terms of diet, various studies have demonstrated that high caloric and fat intake was associated with breast cancer risk, salted food intake with stomach cancer, aflatoxin B1 with liver cancer, and low fruits and vegetables intake with breast and lung cancer. Environmental exposure to indoor and outdoor air pollution, arsenic, radon, asbestos and second hand smoke was shown to increase the lung cancer risk. Reproductive factors such as late age at first childbirth, early menarche, late menopause, oral contraceptive intake, and short duration of lifetime lactation were shown to be associated with breast and/or colorectal cancer. Cancer has clearly become an emerging health threat in Asia and cancer control programs should be actively implemented and evaluated in this region. Various strategies for cancer control have been developed in some Asian countries, including the set-up of national cancer registries, cancer screening programs, education programs for health behavior change, eradication of Helicobacter pylori and vaccination for hepatitis B and C viruses, and human papilloma virus high risk forms. However, more attention should also be paid to low- and medium-resource Asian countries where cancer incidence rates are high, but neither intensive research on cancer for planning effective cancer control programs, nor easy implementation of such programs are available, due to limited financial resources.

Genotype-phenotype relationship between DNA repair gene genetic polymorphisms and DNA repair capacity.

Genotype-phenotype relationships between genetic polymorphisms of DNA repair genes and DNA repair capacity were evaluated in a case-control study of breast cancer. Selected DNA repair genes included were those involved in double-strand break repair (ATM, XRCC2, XRCC4, XRCC6, LIG4, RAD51, RAD52), base excision repair (LIG1), nucleotide excision repair (ERCC1), and mismatch repair (hMLH1). The subjects consisted of histologically confirmed breast cancer cases (n=132) and controls (n=75) with no present or previous history of cancer. Seventeen single nucleotide polymorphisms of 10 genes (ATM -5144A>T, IVS21+1049T>C, IVS33-55T>C, IVS34+60G>A, and 3393T>G, XRCC2 31479G/A, XRCC4 921G/T, XRCC6 1796G/T, LIG4 1977T/C, RAD51 135G/C, 172G/T, RAD52 2259C/T, LIG1 583A/C, ERCC1 8092A/C, 354C/T, hMLH1 5' region -93G/A, 655A/G) were determined by TaqMan assay (ATM) or MALDI-TOF (all other genes). DNA repair capacity was measured by a host cell reactivation assay of repair of ultraviolet damage. The DNA repair capacity (%) did not differ between cases (median 37.2, interquartile range: 23.6-59.6) and controls (median 32.7, interquartile range: 26.7-53.2). However, DNA repair capacity significantly differed by the genotypes of ATM and RAD51 genes among cancer-free controls. Our findings suggest that DNA repair capacity might be influenced by genetic polymorphisms of DNA damage response genes and DNA repair genes.

Lifestyle, genetic susceptibility and future trends of breast cancer in Korea.

Not only the incidence but the mortality of breast cancer has been steadily increasing in Korea over the last twenty years, and it became the most common female neoplasm in 2002. In fact, the increase in the rate of breast cancer mortality in Korea over the past 10 years has been higher than anywhere else in the world, and it is particularly noteworthy that more than half of the incident cases occur among those younger than 50 years of age. The rapid westernization of dietary habits and changes in reproductive behavior of Korean women presumably played a central role in this extraordinary increase in breast cancer occurrence. A large-scale multi-center case-control analysis showed that an older age, a family history of breast cancer, early menarche, late menopause, late full-term pregnancy, never-having had a breast-fed child, and postmenopausal obesity are breast cancer risk factors in Korea. Environmental and genetic factors are known to play interactive roles in human carcinogenesis and recent studies have shown that genetic polymorphisms may predispose individuals to breast cancer via gene-to-environment or gene-to-gene interactions. Thus research into genetic variation in xenobiotic metabolism, estrogen metabolism, DNA repair, cytokine metabolism, or cell cycle control may give insights into both the etiology and prevention of breast cancer. Epidemiologic evidence obtained from migrant and lifestyle change studies and investigations of main risk factors strongly suggests that breast cancer will further increase in Korea. Future predictions point to a 2- to 3-fold increase in incidence by 2020. Here, we briefly introduce health education programs and breast cancer campaigns, in the broad context of the Korean National Cancer Control Program.

Gene amplification using DNA from human spot urine samples.

The purpose of this study was to test the amplification of DNA from human urinary sediment for molecular epidemiological studies. Twenty-six urine samples were obtained from healthy volunteers. Polymerase chain reactions (PCR) for methylenetetrahydrofolate reductase (MTHFR), beta-globin, and N-acetyltransferase 2 (NAT2) was conducted using genomic DNA isolated from the urine. The MTHFR and beta-globin genes were amplified successfully from all the urine DNA samples while the NAT2 gene was amplified in 88.5% of cases. The median yield of DNA was 0.28 microg from the 10 ml urine samples, sufficient amounts of DNA being contained in urinary sediments for amplification of all three genes. This result indicates that urine can be used as a DNA source for PCR-based molecular epidemiological studies.

Genomic epidemiology cohorts in Korea: present and the future.

Human genome epidemiology involves the application of genetic technology to assess the impact of variations at the DNA level on health and disease. Recent developments in molecular biology allow epidemiologists to use biomarkers to determine an individuals predisposition to disease and to detect disease at an early stage. Moreover, advances in genomics and proteomics could play a central role in research into disease prediction and prevention. Large scale population-based cohort prospective studies offer the most comprehensive approach to the delineation of gene function, the effects of the environment, and their interactions. The Korean Multi-center Cancer Cohort (KMCC), under construction since 1993, is the first multi-center prospective cohort to identify risk factors for cancer in Korea. Data on general lifestyle, physical activity, diet, reproductive factors, and agricultural exposure are obtained through direct interview using a structured questionnaire. Anthropometric measurements and clinical laboratory findings are also collected using a web-based data entry system. Moreover, biological materials have been banked [blood (serum, plasma, buffy coat, packed erythrocytes) is stored at -70 degrees C and urine at -20 degrees C] for future analysis. Several other cohorts including the Korean National Cancer Center (KNCC) Cohort, the Korean Health Examinees (KOEX) Cohort, the Korean Health and Genome Epidemiologic Study (KHGES), and the Yang Pyeong Cohort have also been launched since the KMCC cohort was initiated. Even though these cohorts have collected similar data and biospecimen, questionnaires and protocols used have not been standardized. However, these cohort studies are of increased scope and have been designed to detect risk factors for cardiovascular disease, metabolic syndrome, and cancer. Subjects have been followed up actively by health personnel in different regions and by using record linkages with the central cancer registry, and the national death certificate and national health insurance claim databases. As of August 2004, the total number of subjects enrolled in all cohorts with archived biologic specimens was around 80,000. A new genomic cohort has been launched since 2001 in Korea, for which the target number of subjects is 250,000 men and women over the next 5 years. This article describes the goals and the designs of each of the above-mentioned cohorts.

Long-term prediction of female breast cancer mortality in Korea.

Not only the incidence but also the mortality of female breast cancer has been steadily increasing in Korea since the 1980s. Epidemiologic evidence on changes in lifestyle and risk factors related with breast cancer, and data from migrant studies strongly suggest that breast cancer might further increase. In order to estimate the long-term trend in mortality of breast cancer in Korean women, we analyzed age-specific mortality rates for breast cancer over the past 20 years, and made a projection up to 2020 using a linear regression model with the Poisson distribution. The age-adjusted mortality rates for breast cancer per 100,000 persons were 2.84 in 1983, 4.91 in 1993, and 6.26 in 2003. The predicted expected age-adjusted mortality rates for breast cancer are 6.51 for 2005, 7.37 for 2010, 8.22 for 2015, and 9.07 for 2020, with an estimated annual increment of breast cancer mortality of 0.1704. Accordingly, 1,564 women in 2005 and 3,087 in 2020 will be expected to die of breast cancer in Korea. Compared with the rate in 1983, this indicates a more than 3-fold increase by 2020. On the basis of our results, female breast cancer in Korea will linearly increase for the forseeable future if the trend over the past 20 years continues.

Grand challenges in global health and the practical prevention program? Asian focus on cancer prevention in females of the developing world.

In response to the request for 'Breakthrough Questions' for 'Grand Challenges in Global Health' recently published in Nature, the Asian Pacific Organization for Cancer Prevention should focus its attention on what projects are of the highest priority for integration with its Practical Prevention Program (PPP). The most common female cancers in most of the countries of Asia are carcinoma of the breast, followed by the uterine cervix. While the incidences of breast adenocarcinomas are still generally lower than in the Western world they are rapidly increasing, and squamous cell carcinomas of the cervix are a major problem. Clearly there are many areas which would reward research. One factor which appears of major relevance in the mammary gland case is the diet, and particularly the phytoestrogens included in 'tofu', along with physical exercise. The age at which these could be operating needs to be elucidated, with reference to timing of menarche and menopause, and also breast mammographic density, another predictor of likelihood of neoplasia. In the cervix, the predominant influence is well established to be persistent infection with a high risk 'oncogenic' type of human papilloma virus (HPV). Vaccines therefore hold much promise, but a better understanding of the mechanisms underlying spontaneous clearance of both infection and cervical intraepithelial neoplasia (CIN) of different grades is also essential for optimal intervention. The roles of smoking and antioxidant intake in particular deserve emphasis. In Asia, with the considerable variation evident in both breast and cervical cancer incidence rates, as well as in cultural and other environmental factors, we are in a very favourable position to meet two specific challenges: 1). elucidation of how diet in adolescence determines susceptibility to neoplasia of the mammary glands; and 2). determination of what governs persistence of HPV infection. Realisation of these pivotal research aims, with especial emphasis on the context of the PPP, is our shared goal.