Meta-analysis of Association Studies of CYP 1 A 1 Genetic Polymorphisms with Digestive Tract Cancers Susceptibility in Chinese

In recent years, the incidence of digestive tract cancers throughout the world, has shown a marked increase and become a worldwide health burden, especially in developing countries like China. Nevertheless, the incidence has gradually decreased in many western countries. The survival rate of digestive tract cancers in China is far behind europe and the united states. Digestive tract cancers is a heterogeneous, multifactorial disease while its initiation or development can be attributed to the cumulative effect of genetic predispositions, environment


Introduction
In recent years, the incidence of digestive tract cancers throughout the world, has shown a marked increase and become a worldwide health burden, especially in developing countries like China.Nevertheless, the incidence has gradually decreased in many western countries.The survival rate of digestive tract cancers in China is far behind europe and the united states.Digestive tract cancers is a heterogeneous, multifactorial disease while its initiation or development can be attributed to the cumulative effect of genetic predispositions, environment cause of cancer-related deaths in the world with a rising incidence.A growing body of epidemiological evidence has evident regional characteristics.The morbidity and mortality rates of EC in China are the highest in the world, and over 50% of patients have locally advanced fourth most common cancer and the second leading cause Cytochrome P450 superfamily is the important phase CYP1A subfamily includes CYP1A1 which is widely distributed in the lung, kidney, gastrointestinal tract, skin, larynx, placenta, lymphocyte, and brain tissues outside the liver.It is mainly involved in the metabolism of polycyclic aromatic hydrocarbons.Polycyclic aromatic hydrocarbon activation, as a carcinogen, is closely related with the occurrence and CYP1Al is

CYP1A1
studied in relation to cancer risk: and polymorphism.The former occurs in the CYP1A1 gene C variant.polymorphic types by .The polymorphism is also known as the exon7 polymorphism.The amino acids of CYP1A1 exon 7 A 462 of into isoleucine valine.The polymorphism of In the context of the world, extensive case control studies had been conducted to investigate the potential role of the CYP1A1 polymorphisms about digestive tract cancers in China.However, the research results were unclear, which could be due to the differences in the small and genetic interactions power.Meta-analysis might increase statistical power to address this problem.In this paper, the meta-analysis study was performed to explore the relationship between and genetic polymorphisms in the CYP1A1 gene and digestive tract cancers in Chinese populations.

Literature search
According to the search strategy and complement, preliminary screening and full text reading, on the basis of the inclusive and exclusive criteria, six articles were

Discussion
CYP1A1 is an important aspect that plays an essential role in the metabolic activation of major classes of procarcinogens, thus affecting the metabolism of the environmental carcinogens and altering susceptibility metabolism is more than 95% CYP and these variant word, the CYP1A1 gene is considered to be an vital indicator of carcinogens.At present, a series of studies about humans not animals or cellulars have indicated that CYP1A1 polymorphisms may contribute to the risk among different races and ethnicities.on the CYP1A1 polymorphism and EC, GC, CC, HC susceptibility in China and abroad, but these claims were inconsistent as the current research results.The reason might be that there was an obvious contrast between east and west and this difference in populations implied degrees of cancers susceptibility.Some researches had contributed enormously to the understanding of digestive with the association between CYP1A1 polymorphisms and cancers risk among asians failed to cover all conclusive articles published in Chinese databases, and was short of match properly for the Chinese population, not for digestive tract cancers with the worldwide evidence about the Chinese population on the association of CYP1A1 genetic polymorphisms association of two cytochrome CYP1A1 polymorphisms with gastric cancer risk that also failed to show that the genetic polymorphism conferred no there was no association between endometrial cancer risk and the CYP1A1 polymorphism.But their studies had only seven researches, merely for CYP1A1 included in our meta-analysis.At the moment, for the most part, these studies aimed at the all races rather than individual race.Further, we devoted to the individual race, it could get less heterogeneities and more reliable results.
About races, location and environment, the morbidity of a vast country of digestive tract cancers like China could be higher, accompany with different countries.Therefore, our leverage lied in the parallel comparison of the accuracy in Chinese people instead of the world.and ethnic influence, thus increase the reliability of the results.So further epidemiological and molecular biological studies were necessary to clarify the role of CYP1A1 genetic polymorphisms in digestive tract cancers and other countries.Genetic polymorphism referd to one or more allelic mutation genetic variation and the occurrence of multi-peak curve discontinuities in the crowd.For the moment, CYP1A1 genetic polymorphism was one of the most common kinds, which we had discussed in the study group.To evaluate the association of CYP1A1 genetic polymorphism and susceptibility to digestive tract cancers in the Chinese population, we performed an updated systematic meta-analysis.In CYP1A1 genetic polymorphism group, thirteen of eighteen studies showed no correlation between CYP1A1 genetic polymorphism and digestive tract cancers.Subgroup analysis based on ethnicity of controls and tumor type did not discover correlation between CYP1A1 polymorphisms and digestive tract cancers risk.Particularly nine studies of EC were applied for evaluation for the genetic support our result while only two cases were in contrast to it.In GC groups, relationship between genetic polymorphism and digestive tract cancers.Random effects model of CYP1A1 genetic in the overall analysis under all genetic models, respectively, with digestive tract cancers risk in Chinese populations.Subgroup analyses on CYP1A1 substitution gene in EC group indicated that digestive tract cancers risk.Moreover, limited investigative numbers of the case-control followed up ethnicity studies stable risk estimation.substitution in exon activity and therefore the allele would be expected to increase the susceptibility to EC.However, subgroup analyses, GC group and HC group had not found any correlation between them.Two previous meta-analyses our results.Individuals with the substitution in CYP1A1 exon 7 had increased esophageal cancer risk, with ORs , association was found between esophageal cancer risk and genetic parameters.It was regrettable that these were not especially for the Chinese populations.
Tumor has a multi-factor, multi-step of development.It may be involved in gene-gene and gene-environment interactions.some studies without clear explanation for the pathologic diagnostic results of some subjects and each study has its own inclusive criteria.Therefore, some selection bias might be unavoidable.Heterogeneity is an important factor to affect the results of the study.The part of the presence of heterogeneity in all genetic models might be through sensitivity analysis and subgroup, eliminating any document for the reason of the tips in this paper.Publication bias might not exist together with heterogeneity across studies, which increase the statistical power.
As was known with meta-analyses, there were several limitations to the present study.Possible sources of heterogeneity, such as the number of existing clinical trials, level, method, language and the search range limitation might be considered.Then, the consolidation results were from unadjusted estimates and therefore potential covariates.At last, despite gene-gene and gene-environment interactions could be involved in the pathogenesis of digestive tract cancers.The results of our meta-analysis should be interpreted with caution because the lack of representation of population.
In conclusion, our meta-analysis strongly suggested that a meaningful association existed between CYP1A1 polymorphisms and risk of digestive tract cancers and EC in Chinese population.Peoples with null genotypes of CYP1A1 were more susceptible to developing digestive tract cancers.Further studies based on largescale populations and gene-environment interactions are needed to determine, such as community or hospital source populations and selected population with various environmental background.

Figure 2 .
Figure 2. Codominant Model Genetic Model between CC vs TT and CYP1A1 MspI Genentic Polymorphism

Figure 4 .
Figure 4. Begg's Funnel Plot of Codominant Model Genetic Model (CC vs TT) in CYP1A1 (MspI Genentic Polymorphism Group written in Chinese and English languages.Published literatures from PubMed, Embase, CBM, Chinese Data and other Chinese databases were retrieved by keywords and their combinations: CYP1A1, esophageal cancer, gastric cancer, colorectal cancer, liver cancer and hepatic carcinoma, gene polymorphism and China or Chinese.Meanwhile, reference lists of the relevant articles were also collected.The inclusion and exclusion criteria of this meta-

Table 2 . Case-control Studies about CYP1A1 Ile Val Substitution Polymorphisms and Digestive Tract Cancers
there was little association between CYP1A1 gene polymorphism and digestive tract cancers risk including EC, GC, CC, and HC.However, there was association or HC in CYP1A1 polymorphisms and EC, GC and CC in CYP1A1 polymorphisms.The Partial forest Sensitivity analyses CYP1A1 two genetic polymorphisms, a single study method was deleted each time toORs.The corresponding pooled ORs were not markedly altered under all models in both the overall analyses and the subgroup analyses, with more than two studies.It indicated that our results were statistically robust.Looking for heterogeneity: all studies were eliminated one by one in the genetic model, these analyses, however, the results did not altered substantially under any genetic models.detectedforstudies published on polymorphism vs TT, P E vs TC+TT, P ECC vs TT, P E vs TT, P E vs AA, P E vs E <0.05 suggested the presence of because the funnel plots appeared to be approximately

Table 4 . Summary of Pooled ORs and 95%CI for CYP1A1 Ile/Val Genetic Polymorphism
the polymorphisms of phase i and phase ii metabolic genes and esophageal carcinoma susceptibility.Shiyong Xin Nao Fei Xue Guan Bing Za Zhi, 16 and risk factors that associated with the susceptibility of gastric cancer.Zhenghua Xiao Hua Za Zhi, 27 of CYP1A1 Cancer Risk: Evidence-based Meta-analyses.Res, 40 Q between gene polymorphism of CYP1A1 genetic susceptibility of primary hepatocellar carcinoma.Zhong Liu Fang Zhi Za Zhi, 8, 572-4.
carcinoma in Taiwan females.Cancer Lett, 30 genetic polymorphisms and risk of hepatocellular carcinoma among chronic hepatitis Bcarriers.Br J Cancer, 80 between the functional polymorphisms in the estrogen-