Study On Environmental Exposure, DNA Adducts And Cancers

Cancer is a leading disease affecting people's health seriously. The report by WHO shows, from a total of 58 million deaths worldwide in 2005, cancer accounts for 7.6 million (or 13%) of all deaths. The main types of cancer leading to overall cancer mortality are: lung cancer(1.3 million deaths/year), stomach cancer(almost 1 million deaths/year), liver cancer(662 thousand deaths/year), colon cancer(655 thousand deaths/year) and breast cancer(502 thousand deaths/year). The death number of cancer increases continuously in China and now cancer is the first leading cause of all death, especially in west China and country.DNA adducts are biomarkers for exposure and risk in research on tumour pathogenesis. The sources of DNA-binding agents are endogenous and exogenous or both. Many carcinogens exert their biological effects through the formation of DNA adducts by metabolically activated intermediates. DNA adducts are general forms of DNA damage. Mutations around adducted bases and chromosome damage may arise when adducts are not repaired or misrepaired. Then tumour may occur. Testing levels of DNA adducts and compounds for its formation, which gives information to mechanisms of mutagenesis and carcinogenesis and provides a method of evaluating individual repair capability to DNA damage, has important significancy in environmental risk estimation and tumour research.We conducted a population-based case-control study in Jiashan County to investigate the levels of DNA adducts in normal population, explore the relations between environmental exposure and cancers(Iung, breast, colon, rectal, and gastric cancer), discuss connections betweensome exposure factors and DNA adducts and evaluate validity of DNA adducts as biomarkers in tumor progress.Materials and MethodsStudy objects originated from a cohort-study population with 64693 people. Prevalent cases including lung, breast, colon, rectal and gastric cancer, who had been diagnosed during 1 st May 1990 to 30th May 2005, composed the case group;controls were stratified sampled from cohort population according to sex and age. Two investigations were implemented in 2002 and 2005, and 40 lung cases, 84 breast cases, 93 colon cases, 114 rectal cases, 91 gastric cases and 847 controls respondented to main questionnaires. At last, blood samples of 351 cases including 40 lung cases, 74 breast cases, 72 colon cases, 90 rectal cases, 75 gastric cancers and 694 controls were selected for DNA adducts because of adequate blood.All subjects were interviewed face-to-face by trained interviewers. A constructed questionnaire were pre-investigated and included demographic condition, diet, life style and history of selected diseases, et al. Genomic DNA was extracted from whole frozen blood samples using improved salting out procedure. PAH-DNA addcts were analyzed by competitive ELISA.After verification and code, the questionnaires were inputted using EPIDATA 3.0. DNA adduct levels with non-normalized distribution were expressed using median and interquartile range. The differences were examined by nonparametric tests;adducts levels were also rank transformed in order to every two group compare using LSD test of one-way ANOVA. Cases and controls were 1:2 matched according to gender and age. Cox regression were used to fit 1:2 conditional Logistic regression. All statistical analyses used SPSS 13.0 software.All investigator trained before investigation and questionnaire standards were established. For each food, amounts consumed were estimated according to models of the more frequently consumed foods for the accuracy of survey. Questionnaire were logical checked everyday and interview would be executed over again if there were something wrong. After investigation, 10% objects were re-interviewed on phone. The numbers of blood and questionnaire were checked erery day. Lab tests used blind method.Results1. Distribution of DNA adducts in controlsThere were 694 controls in this study. Median of DNA adducts level was 5.15 fmol/ugDNA and differences of adducts levels between sex, age, occupation, year of residence, cook year, rangehood, brawn, fumed fish, kipper, fried fish, fried beancurd, smoke, types of cigarette holder, smoke inhaling, years of smoke, number of cigarette erery day, drink and years of drink were not significant (f>0.05).2. DNA adducts and cancersOR(95%CI) of DNA adducts to lung cancer, breast cancer, colon cancer, rectal cancer and gastric cancer were 1.259(1.129-1.404), 1.123(1.052-1.198), 1.134 (1.061-1.213), 1.171(1.092-1.171) and 1.132(1.059-1.209) respectively and ?<0.05. There were significant positive association between them.3. Relationships between exposure factors and cancersIn lung case-control study, OR(95%CI) of smoke inhaling, 20~cigarette/day and drink to lung cancer were 10.781(1.367-85.023), 2.811(1.339-6.195) and 2.522(1.018-6.252) respectively .In breast case-control study, OR(95%CI) of farmer, living 60~years, kipper, fried fish and fried beancurd to breast cancer were 0.315(0.152-0.654), 0.100(0.012-0.856), 2.765(1.502-5.092), 2.951(1.609-5.431) and 1.967(1.117-3.464) respectively (/^0.05). Farmer and living 60- years had negative relations with breast cancer, while kipper, fried fish and fried beancurd had positive relations with breast cancer.In colon case-control study, OR(95%CI) of farmer to colon cancers was 0.328(0.152-0.708).In rectal case-control study, no relationships were found between exposure factors and rectal cancer.In gastric case-control study, OR(95%CI) of brawn to gastric cancer was 2.019(1.103-3.697).4. Relationships between exposure factors and DNA adductsIn lung case-control study, there were significant differences of DNA adducts levels in between 20~cigarette/day and 1-cigarette/day (P<0.05). In group of 20~cigarette/day, OR(95%CI) of DNA adducts to lung cancer was 1.107(1.010-1.213).In colon case-control study, there were significant differences of DNA adducts levels between farmers and other occupation, 20~cigarette/day and 1-cigarette/day. In group of other occupationand 20~cigarette/day, OR(95%CI) of DNA adducts to colon cancer was 1.085(1.010-1.165) and 1.078(1.012-1.184) respectively.There appeared no connections between exposure factors and DNA adducts in breast, rectal or gastric case-control study.ConclusionsThere are no significant differences of DNA adducts levels in sex, age, occupation, year of residence, cook year, rangehood, brawn, fumed fish, kipper, fried fish, fried beancurd, smoke and drink.Smoke inhaling, 20~cigarette/day and drink are risk factors for lung cancers. Fanner and living 60~years are protective factors for breast cancers and kipper, fried fish and fried beancurd are risk factors for breast cancers. Farmer is protective factor for rectal cancer. Brawn is risk factor for gastric cancer.In lung case-control study, DNA adducts are significantly higher in people who smoke 20~cigarette/day than those smoke 1~ cigarette/day. In colon case-control study, DNA adducts are significantly higher in other occupation than farmers and also higher in people who smoke 20~cigarette/day than those smoke I~ cigarette/day.DNA adduct is risk factor for lung, breast, colon, rectal and gastric cancer. So it is feasible that DNA adduct become an index of evaluating cancer risk.