Study On The Association Of Lung Cancer With Cigarettes Consumption And Cytochrome P450 CYP1A1 M1 Polymorphism

BackgroundIn recent decades, the mortality rate of lung cancer has been increasing very quickly. It has been identified as a major health issue confronting both more developed and less developed countries. It has also become the most common cause of death in male and the second common cause of death in female according to the report of WHO in 2005. Male lung cancer incidence/mortality rate is continuing to increase in China. However, mortality rate in male fluctuates very small since 2001 in Taiwan of China. Although rates of lung cancer incidence tend to be relatively low among female, rates are beginning to increase both in Mainland and Taiwan of China. In contrast, the incidence/mortality rate of lung cancer in male has reached a plateau and now is decreasing in United States. Whereas the number of new/death cases in women continues to increase. In conclusion, the trend of lung cancer mortality in Mainland of China, Taiwan of China and United States are different.Cumulative studies on cancer show that carcinogenesis is a multifactor and multistage process, and haven't been expressed explicitly. However smoking, which is supported by abundant researches, is one best established risk factor for lung cancer. Tobacco consumption in less developed countries is increasing markedly. China is the largest producer of cigarettes. What'smore, China is the country with the highest tobacco consumption. There are almost one-third of cigarettes in the world produced in China, and there are one-third of cigarettes in the world consumed by Chinese. In contrast, consumption on cigarettes has declined in more developed countries due to the impact of medical research, public health education and government regulation in recent yeas. There are nine percent of cigarettes in the world consumed by Americans according to the report of FAO. In conclusion, cigarettes consumption is different between China and United States.Epidemiology studies have showed that the risk of lung cancer varied in different ethnic people. There are only ten to fifteen percent of smokers suffer from lung cancer, and it perhaps can be explained by individual susceptibility. Carcinogen metabolism involves two stages: phase I enzymes promote the activation of pro-carcinogens. Meanwhile, phase II enzymes generally act as inactivating enzymes.Some studies showed that there was association between genetic polymorphisms in CYP1A1 and lung cancer, while other studies showed opposite results. The results of the association between CYP1A1 and lung cancer were also inconsistent. CYP1A1 gene, as one of cytochrome P450 family, there are four alleles (m1, m2, m3 and m4) polymorphism being studied at present. Only CYP1A1 ml polymorphism is studied in this paper.ObjectivesStudy on the association of lung cancer with cigarettes consumption and cytochrome P450 CYP1A1 ml polymorphism between Chinese and Americans. Provide some clues to study why there are different trend in lung cancer mortality between Chinese and Americans.①To describe the changing trend and characteristics of cigarette production and consumption in Mainland of China, Taiwan of China and United States.②To describe the changing trend and characteristics of average production and consumption of cigarettes in Mainland of China, Taiwan of China and United States.③To study on the association of lung cancer in male with average cigarettes consumption between Chinese and Americans.④To study on the association of lung cancer with cytochrome P450 CYP1A1 ml polymorphism in Asian subgroup and Non-Asian subgroup.Material and MethodsApply ecological study and Meta-analysis this paper, which includes two parts. One part is ecological study on cigarettes consumption and lung cancer, which involves:1.select study object,2.collect data about cigarettes and lung cancer,3.analyse data, mainly includes correlation and regression methods. The other part is Meta-analysis on association between genetic polymorphisms of CYP1A1 ml and lung cancer, which involves: l.select study object, 2.collect data about CYP1A1 ml and lung cancer, 3.select data, 4.abstract data, 5.analyse data. Statistical analysis was performed in SPSS13.0 and Revman4.0.Main Results1. Ecological study on average cigarettes consumption and lung cancerThe Main results include:①Cigarettes production and consumption increased nearly three times from 1975 to 2005 in Mainland of China. Cigarettes production and consumption varied very small from 1997 to 2004 in Taiwan of China. Cigarettes production and consumption increased from 1970s to 1990s, but it declined from 1990s to 2000s.②Average cigarettes conduction and consumption of Americans are higher than those of Chinese with a decline trend. Average cigarettes conduction and consumption of people from Mainland of China and Taiwan of China are similar, but the trend is different. Average cigarettes conduction and consumption of people from Taiwan of China declined, while that of people from Mainland of China increased. ③ Correlation analysis showed the risk of lung cancer in male increased significantly with the rising of average cigarette consumption(r=0.87,P<0.001). But lung cancer is no significant statistic increase in parallel to average cigarette consumption in Taiwan of China and America(Taiwan of China r=0.26,P=0.25, United States r=-0.13 P=0.64).2. Meta-analysis in association between genetic polymorphisms of CYP1A1 ml and lung cancerThere are 20 related studies met the inclusion criteria. All the studies with controls were in Hardy-Weinberg equilibrium. The main results involve:①There is no significantly statistic risk of lung cancer associated with individuals with the m1/ml and wt/ml genotype compared to individuals with wt/wt genotype (the pooled OR= 1.17, 95%CI:0.96～1.42, P=0.13). In thesubgroup analysis, the results showed that individuals with the m1/ml and wt/ml genotype (compared to individuals with the wt/wt genotype) has no significantly statistic risk to lung cancer in Chinese or Americans (the pooled OR= 1.28,95%CI: 0.98～1.69, P=0.07 and the pooled OR= 0.96, 95%CI: 0.80～1.15, P=0.64, respectively).②There is no significantly statistic risk of lung cancer associated with individual with the m1/ml genotype compared to individuals with the wt/wt and wt/ml genotype (the pooled OR= 1.16,95%CI:0.92～1.46, P=0.22). In the subgroup analysis, the results showed that individuals with the m1/ml genotype (compared to individuals with the wt/wt and wt/ml genotype) has no significantly statistic risk to lung cancer in Chinese or Americans (the pooled OR= 1.22, 95%CI: 0.91～1.63, P=0.18 and the pooled OR= 1.17, 95%CI: 0.79～1.73, P=0.44, respectively).③There is no significantly statistic risk of lung cancer associated with individual with the ml /ml genotype compared to individuals with wt/wt genotype (the pooled OR= 1.11,95%CI:0.90～1.37,P=0.33). In the subgroup analysis, the results showed that individual with the m1/ml genotype (compared to individuals with the wt/wt genotype) has no significantly statistic risk to lung cancer in Chinese or Americans (the pooled OR= 1.16,95%CI: 0.90～1.48,P=0.25 and the pooled OR=0.99, 95%CI: 0.66～1.48,P=0.96, respectively).ConclusionsThe main conclusions include:①There is line correlation between average cigarettes consumption and lung cancer mortality in male in Mainland of China. Lung cancer mortality in male increased with average consumption of cigarettes. While there is not line correlation between average cigarettes consumption and lung cancer mortality in male in Taiwan of China and United States.②CYP1A1 ml polymorphisms are not associated with lung cancer risk in Chinese and Americans.