| [Objective] To provide scientific evidence for the prevention and control of lung cancer in urban Shanghai, we conducted a statistical analysis to investigate the possible environmental factors and a nested case-control study on the nucleotide polymorphisms (SNPs) of genes in translesion synthesis (TLS) pathway and the risk of male lung cancer by means of using a prospective cohort study.[Methods] 61500 participants aged 40 to 74 were involved in the Shanghai Men's Health Study (SMHS), a prospective male cohort study was established during 2002 to 2006 in urban Shanghai. The information on demographic data, smoking, alcohol drinking, tea drinking, diet, physical activity, prior lung diseases, anthropometric measures and so on were collected at baseline.323 newly diagnozed patients of lung cancer were identified in the cohort by December 31,2008. Diagnosis of lung cancer was confirmed by the collection and review through medical abstract, clinical imaging examination or pathological information. Person-years of follow-up were calculated for each participant from the date of the baseline interview to the dates of cancer diagnosis, death, lost to follow-up or Dec 31,2008. The Cox proportional hazard regression model was used in our analysis to obtain hazard ratio (HR) and its 95% confidence intervals (95%CIs) after adjusting for some potential confounding factors. For the nested case-control design, there were 224 patients of lung cancer who donated blood samples. For each case, two controls were randomly matched on age (within 2 years) and date of biospecimen collection (within 1 month). The genonmic DNA was extracted by using Promega genomic DNA extraction reagent box, and the genotypes were performed using ABI Prism 7900HT fluorescent quantitative PCR system. The odds ratio (Odds ratio, OR) and its 95%CI were estimated by unconditional logistic regression model to measure the relationship between gene polymorphisms and risk of male lung cancer.[Results] By December 31,2008,273 645.39 person-years were followed for the cohort, and average 4.45 person-years was estimated per subject.323 incident cases of lung cancer were diagnosed in the cohort. The density rate was 11.80 per 100000 person-years.Decreased risks of lung cancer were observed for the smokers with higher groups of weight, body mass index, waist circumference at baseline, body mass index and weight at 40-year-old (P trend<0.05). Compared with never smokers, former smokers and current smokers were linked to a significantly increased risk of male lung cancer, with the adjusted HRs 2.70 (95%CI:1.81-4.00) and 3.78 (95%CI:2.66-5.39), respectively. Heavy alcohol drinkers were associated with an increased risk of lung cancer among adult men (HR=1.32,95%CI:1.02-1.71). Chronic bronchitis significantly increased the risk of male lung cancer (HR=1.73,95%CI:1.25-2.39). No statistical significant associations were found for tea consumption, physical activities in adolescent and in adulthood in our analysis.The genes of DNA translesion synthesis (TLS) pathway were considered in our study for REV1, REV3, POLH, POLI, POLK and PCNA. The molecular epidemiological studies indicated that the gene polymorphsims of POLK (rs1018119), PCNA (rs25406) and PCNA (rs3729558) were associated with increased risk of lung cancer. Compared with the homozygous genotype (A1A1), the ORs of the mutant genotypes among above three SNPs (A1A2/A2A2) were 1.55 (95%CI:0.94-2.57), 2.40 (95%CI:1.17-4.92) and 2.06 (95%CI:0.91-4.63), respectively. In contrast, the rs3730668 of POLI gene was linked to the reduced risk of male lung cancer, and the OR was 0.49 (95%CI:0.23-1.04).Regarding to the joint analysis of genes and environmental factors, the lung cancer risk of the group, which had heavy smoking and carrying the mutant genotypes of the following SNPs, such as rs3087386, rs462779, rs8305, rs1018119, rs5744533, rs25406, rs3729558, was higher than the effect of mutant genotypes or smoking alone. And for the following SNPs, such as rs2290257, rs3792136, rs465646, rs6941583 and rs3730668, the risk was just higher than the mutant genotype alone, but lower than the smoking alone. No combined effect was found for the alcohol drinking.[Conclusion]1. Higher body mass index, weight and waist circumference may be associated with reduced risk of lung cancer, especially for male smokers.2. Smoking is a mainly risk factor for male lung cancer, and quit smoking will reduce the risk.3. Heavy alcohol drinking may increase the risk of male lung cancer among smokers.4. The protective effect between tea consumption and male lung cancer risk was not observed in our data.5. Chronic bronchitis may increase the risk of male lung cancer. 6. Participating in physical exercise, leisure time and daily physical activities in adulthood may not be associated with the protective effect against lung cancer among males.7. The mutant genotypes (A1A2/A2A2) of POLK rs1018119, PCNA rs25406 and PCNA rs3729558 may increase the risk of male lung cancer. In contrast, POLI rs3730668 gene's mutation may decrease the risk of male lung cancer.8. Gene-environment interaction analysis showed that there were combined effects of smoking and genes for the risk of lung cancer (except for rs5744724), but not for alcohol drinking.
|
PDF Full Text Request