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.