Association Study On Organochlorine Compounds And Colorectal Cancer Risk

BackgroundColorectal cancer is one of the most common malignant tumors of digestive tract worldwide. Colorectal cancer is especially common in the North America, Australia and Western Europe, while the incidence tends to be low in Africa and Asia. Recently, with changes of diets and behavior habits, incidence rate of colorectal cancer has been increasing rapidly in China. It is the third prevalent cancer both in males and females with an increasing incidence, of which the estimates in 2005 were 15.0 and 9.7 per 100,000 for males and females, respectively.Colorectal cancer is the result of both effect of environmental factors and genetic susceptibility. Most epidemiological studies have reported that 70 percent of colorectal cancer could be explained by the environmental factors. It is widely accepted that environmental factors, such as diet (high fat and high energy), smoking, drinking, overweight and history of intestinal diseases, play key roles in the susceptibility to colorectal cancer development and progression.Diet is also an important source of exposure to many synthetic organic chemicals used in industry, agriculture, or accidentally released to the environment. Among them, polychlorinated biphenyls (PCBs), the pesticides dichlorodiphenyltrichloroethane (DDT) and lindane [including a-,(3-,y-,8-hexachlorocyclohexane (HCH)] have been classified as "probably" or "possibly" carcinogenic to humans[International Agency for Research on Cancer (IARC)]. Despite reductions in their use and fugitive release, organochlorine compounds remain one of the most important groups of persistent pollutants to which humans are exposed. Many epidemiological studies have reported organochlorine compounds can increase risk of several cancers, including colorectal cancer.Thus, we conducted a population-based case-control study in Jianshan County using serum organochlorine compounds levels as exposure markers, in order to assess the risk of colorectal cancer with exposure to these chemicals, and their potential interactions with environmental factors or genetic polymorphisms of drug-metabolizing enzyme genes in colorectal carcinogenesis.Methods64 693 persons from 10 districts in Jiashan County, Zhejiang Province, who took part in the colorectal cancer screening during 1989 to 1990, consisted of the cohort population of this study.207 eligible patients with confirmed colorectal cancer reported by the cancer registry system were included as cases in our study. As a result of failure in assay detection,202 cases comprised the subjects in this analysis ultimately. Efforts were made to 1:2 individual-match the cases and controls by age with 5-year intervals and gender. A total of 404 controls who did not have a history of cancer were selected randomly from the cohort population during the same period. All individuals were ethnic Han Chinese and residents in Jiashan County.They were interviewed face-to-face through a constructed questionnaire, including demographic characteristics, lifestyles, and disease history, by professionally trained interviewers. In addition, a 5 ml venous blood sample was draw from each individual with the permission. Organochlorine compounds (includingα-,β-,γ-,δ-HCH, DDT, DDE, PCB28,52,101,118,138,153,180) were analyzed by gas chromatography after serum samples were subjected to liquid-phase microextraction.Basic variables of controls and cases were compared by Pearson's x2tests. Independent-samples t test analysis was used to compare the mean concentrations of organochlorines between cases and controls. Organochlorine concentrations in serum displayed log-normal distributions and therefore, these statistical analyses were performed using the natural logarithm of organochlorines concentrations. In addition, organochlorine compounds concentrations were categorized into three groups using tertiles based on the distributions among control subjects. Conditional logistic regression analysis was performed to calculate the odds ratios (ORs) with 95% confidence intervals (95% CIs). Stratified analyses were used to explore the interaction between organochlorine compounds levels and environmental factors, also between organochlorine compounds levels and genetic polymorphisms. P value of the interactions was evaluated by likelihood test. All P-value were two-sided.Results1. Environment exposures and colorectal cancerThe demographic characteristics did not differ significantly between cases and controls. No association was found between history of smoking, alcohol drinking, tea drinking and the risk of colorectal cancer. However, as adjusted by age, sex, marriage status, education level, occupation, BMI, smokers (>35 years) had a significantly increasing risk of colorectal cancer comparing with non-smokers (OR:2.20,95% CI: 1.13-4.27)2. Organochlorine compounds and colorectal cancerThe serum levels of organochlorine compounds, includingα-HCH,β-HCH,γ-HCH,δ-HCH, P-p'DDT, P-p'DDE, PCB28, PCB 52, PCB101, PCB118, PCB138, PCB153, PCB180, also did not differ significantly between cases and controls. However, when stratified analyse was used, we found increased risk of colorectal cancer was associated with high levels of y-HCH (>4.03 ng/g), P-p'DDE (>1157.61ng/g), PCB118 (>36.79ng/g), PCB180 (>8.09ng/g) and total PCBs (>341.53ng/g). The ORs were 1.36 (95%CI:1.04-1.77),1.31 (95%CI:1.01-1.71),1.36 (95%CI:1.05-1.67),1.45 (95%CI: 1.06-1.99) and 1.35 (95%CI:1.00-1.82) in each highest group, respectively.3. Interaction of lifestyle factors and organochlorine compoundsIndividuals with a history of smoking and exposed of high level of PCB138 had a significantly increasing risk of colorectal cancer (OR:1.96,95% CI:1.19-3.23). Interactions existed between smokers (>35 years) and high levels of a-HCH, P-p'DDT, P-p'DDE, PCB52, PCB 138, PCB 180 and total PCBs, respectively. The ORs were 2.00 (95% CI:1.09-3.65),1.82 (95% CI:1.03-3.22),1.95 (95% CI:1.11-3.43),1.92 (95% CI: 1.08-3.44),1.93 (95% CI:1.02-3.66),2.61 (95% CI:1.33-5.11) and 2.44 (95% CI: 1.35-4.41). Interactions also existed between heavy smokers (>20 cigarette per day) and high levels of total HCH, P-p'DDE, PCB118, PCB180 and total PCBs, and the ORs were 1.82 (95%CI:1.00-3.32),2.03 (95%CI:1.14-3.60),2.08 (95%CI:1.13-3.83),2.72 (95%CI:1.41-5.23) and 1.92(95%CI:1.08-3.39), respectively.No significant associations were found between alcohol drinking and organochlorine compounds with the risk of colorectal cancer. However, the risk of colorectal cancer increased when alcohol drinking (>31 years), combined with high levels of PCB52 and PCB180, respectively. The ORs were 1.94 (95%CI:1.00-3.78) and 1.77(95%CI:1.05-3.28).What's more, individuals with a history of tea drinking and exposed of low levels of P-p'DDT decreased colorectal cancer risk (OR:0.59,95%CI:0.37-0.94). Individuals without a history of tea drinking and exposed of high levels of PCB180 increased colorectal cancer risk (OR:1.51,95%CI:1.03-2.42).4. Interactions between genetic polymorphisms and organochlorine compoundsNo significant association was found between phaseⅠenzymes, phaseⅡenzymes gene polymorphisms and colorectal cancer risk.The risk of colorectal cancer increased significantly when individuals with CYP1A2 C734A variant, combined with high levels ofγ-HCH, total HCH, PCB118, PCB180, total PCBs, middle level of PCB138, respectively. The ORs were 1.55 (95%CI: 1.04-2.30),1.62 (95%CI:1.04-2.51),2.53 (95%CI:1.25-5.10),1.77 (95%CI:1.14-2.74), 1.80 (95%CI:1.17-2.79) and 2.50 (95%CI:1.24-5.05). Also, the risk increased when individuals with CYP2E1 Rsa I variant, combined with y-HCH, PCB138, PCB180 and total PCBs, respectively. The ORs were 1.52 (95%CI:1.02-2.25),1.61 (95%CI: 1.03-2.52),1.67 (95%CI:1.08-2.59) and 1.57 (95%CI:1.02-2.42). In addition, individuals with CYP1B1 C1294G variant, together with high levels of a-HCH,β-HCH,γ-HCH, total HCH, P-p'DDT, P-p'DDE, PCB118, PCB180 and total PCBs, ryespectively, elevated the risk of colorectal cancer. The ORs were 1.55 (95%CI: 1.03-2.35),1.55 (95%CI:1.00-2.41),1.85 (95%CI:1.18-2.89),1.68 (95%CI:1.05-2.69), 1.67 (95%CI:1.10-2.52),1.57 (95%CI:1.03-2.39),1.74 (95%CI:1.11-2.72),1.75 (95%CI:1.10-2.77) and 1.89 (95%CI:1.19-3.00).GSTM1-deleted genotype associated with high levels y-HCH, PCB28, PCB180, respectively, had a significantly increasing risk of colorectal cancer. The ORs were 1.59 (95%CI:1.08-2.36),1.47 (95%CI:1.09-2.19) and 1.60 (95%CI:1.17-2.31). Additionally, UGT1A6 variant associated with high level of y-HCH, SULT1A1 variant associated with middle level of PCB138, SULT1A1 variant associated with middle level of PCB180, all elevated the risk of colorectal cancer. The ORs were 1.63 (95%C7: 1.07-2.48),2.13 (95%CI:1.11-4.12) and 1.78 (95%CI:1.02-3.08), respectively.ConclusionsConclusions are drawn from the results of the population-based case-control study as followed:1. Smoking (>35 years) may contribute to the colorectal cancer predisposition.2. High levels of y-HCH, P-p'DDE, PCB118 and PCB180 may have effect on colorectal cancer.3. Interactions of smoking, especially its duration (>35 years) and amount (>20 cigarette per day), and high levels of organochlorine compounds may have influence on colorectal cancer. In addition, alcohol drinking may have similar effect.4. Phase I, phase II enzymes genetic polymorphisms may have a modifying effect on the risk of colorectal cancer associated with exposures to organochlorine compounds.