| Background：Colorectal cancer (CRC) is the most common malignant tumor ofthe gastrointestinal tract, the early symptoms are not obvious, with thetumor increases and changes in bowel habits, stool, diarrhea, alternatingdiarrhea and constipation, local symptoms such as abdominal pain, lateshow anemia, the weight is light and other systemic symptoms. Themorbidity and mortality after gastric cancer, esophageal cancer andprimary liver cancer in the digestive system malignant tumor.Colorectal cancer accounts for10~15%of malignant tumors, isthe world’s third most common cancer. The incidence rate in NorthAmerica, Oceania is the highest, the countries in Asia and Africa isrelatively lower, only in Europe, the patients who got the disease wasmore than370000people. In China, the median age of colorectal cancerwas58years old, more than Europe and the United States; in recentyears, the domestic statistics shows that the median age has over60years old.The incidence is higher in men than in women, about1.3folds.Colorectal cancer is as yet ranked No. fifth tumor, but the growth rate isvery fast, especially in some big cities. This increase is related to the lifelevel and diet structure change. For example, the last century90’s and70’s, colon cancer increased104%in male, increased99%in female inShanghai.The average annual increase of colon cancer is about4%,other big city is also. From a worldwide perspective, China is a low incidence area of colorectal cancer. Currently in China colonrectalcancer is the fifth common malignant tumors, but the upward trend inincidence, especially colon cancer incidence grows rapidly, the growth isfaster in big city. In short, the last century90’s compared with70’s, theincidence of colorectal cancer in the city rose31.95%,8.51%rose inrural areas. China sees more rectal cancer, in Europe and the UnitedStates colon cancer is more common, the geographical distribution ofmorbidity and mortality is: eastern coastal area is higher than in inlandNorthwest area, the morbidity is highest in the middle and lower reachesof Yangtze River.On the whole, Compared with western world,there arethree epidemiological characteristics of rectal cancer in China:1, rectalcancer incidence is higher than that of colon cancer, about1.5:1; thelatest data shows that the incidence of colorectal cancer is approaching,some areas have close to1:1, is mainly caused by rectal cancer incidencerates increased; the low rectal cancer accounted for a high proportion,accounting for60%~75%in rectal cancer, most cancer can be touchedon rectal examination; rectal cancer in young people (G30years old) hasa high proportion, about10%to15%. The overall5year survival rate inrectal cancer after radical resection is about60%,5years survival ratepostoperative is80%-90%in early rectal cancer.With the development of human genome and post genome projectresearch, gene polymorphism as the life sciences "strategic" research hasattracted more and more attention to life scientists. It is stated in thehuman disease, poison susceptibility and tolerance, diversity of clinicalmanifestations of diseases, as well as the response to the drug therapyplays an important role. Through the study ofgene polymorphism, canreveal the existence of the nature of the differences between functionand effect of human populations of bioactive substances from gene level; clarify the relationship between genotype and phenotype in theunderstanding of disease mechanism, prediction has an important role inthe prognosis of diseases and so on; drug metabolism genepolymorphism can be erased and rate metabolic effects of drugs, whichaffects the treatment result.According to the characteristics of medicinegene polymorphism, will make theclinical treatment in accordance withindividual requirements; gene polymorphism in the occupation diseasemedicine has more practical significance. For susceptibleanalyte geneand biomarkers of susceptibility, some carrying sensitivegenotypeperson differentiates, take preventive measures, improve theefficiency ofoccupation hazard prevention work; use of various positionknown manypolymorphic markers, by linkage analysis in families,pathogenic gene or genes can be found multi gene disease position, andprovide the basis for isolation and cloning of their.Polymorphism refers to a group of random mating, the samelocusgenotype2or more. In the crowd, nucleotide sequences ofindividual genes exist differences called gene (DNA) polymorphism.This kind ofpolymorphism can be divided into two categories, namelythe DNA polymorphism and length polymorphism. Thehuman genepolymorphism in the human disease, poison susceptibility and tolerance,diversity of clinical manifestations of the disease, as well as theresponse to the drug therapy plays an important role. Clinical researchrelated to early gene polymorphism is started from the HLA gene,analysis of the effect of genotype on disease susceptibility, such asclosely related to the incidence of HLA-B27alleles and ankylosingspondylitis, can serve as a basis for diagnosis. Through the study of genepolymorphism, can reveal the existence of the nature of the differencesbetween function and effect of human populations of bioactive substances from gene level.Genetic variations in DNA repair genes affect repair of bulky DNAlesions and maintenance of genomic stability, and thus cancer risk.Polymorphisms in DNA repair genes involved in nuclear excision repair(NER) could alter the efficacy of DNA repair, and thus influenceindividual susceptibility to colorectal cancer. Several types of genes areknown to be involved in NER, including DNA uncoiling (ERCC2andERCC3), incision (ERCC1-ERCC4/XPF and ERCC5/XPG), excision,elongation, and ligation. Studies on association between variants in DNArepair genes and colorectal cancer risk have gained inconsistent results.ERCC1has been mapped to chromosome19q13.2-q13.3; itincludes ten exons and encodes297acetaldehyde ammonia products,which comprises a subunit of the NER complex that performs anincision step of the NER pathway. Previous studies have found that aheterodimer of ERCC1catalyzes the5’ incision in the process ofexcising DNA lesions and repairing inter-strand crosslinks.Polymorphisms in ERCC1may alter the DNA repair capacity and resultin different biological responses to DNA damage, thus affectingsusceptibility to cancer. Therefore, ERCC1polymorphisms canpotentially be used to identify high-risk individuals. Previous studieshave indicated that the ERCC1rs3212986and rs11615polymorphismsmay be associated with risk of cancers such as gastric, breast, adultglioma and lung. We found that the rs3212986and rs11615polymorphisms were associated with increased colorectal cancer risk.Previously, one study indicated thatERCC119007T>C polymorphismwas associated with increased risk of colorectal cancer, while anotherstudy did not find a significant association between colorectal cancerrisk and ERCC1polymorphisms. The discrepancy in the results may be explained by the differences in subjects’ ethnicities, source of controlsubjects, sample size, or chance. Further studies are needed to confirmthe association between ERCC1polymorphisms and colorectal cancerrisk.XPF is located on chromosome16p13.12, contains11exons andspans approximately28.2kb, and is involved in the5’ incision made inthe NER pathway. XPF is reported to have a role in removing DNAinterstrand cross-links and DNA double-strand breaks. XPF has beenlinked to susceptibility to xeroderma pigmentosum and a rare recessivesyndrome that includes photosensitivity and malignant tumordevelopment. Polymorphisms in XPF may also be associated withglioma and gastric cancer. Wang et al. reported that polymorphisms inrs1800067and rs2276466were correlated with a1.31-3.77fold risk ofglioma. However, others have obtained contradictory results. In ameta-analysis with47,639cancer cases and51,915controls, Shi et al.,reported that polymorphisms of XPF had no association with overallcancer risk. Similarly, we found no significant association between XPFrs2276466or rs6498486polymorphisms and risk of colorectal cancer.Objective:To further assess the association between ERCC1-XPF variants andrisk of colorectal cancer in a Chinese population, we conducted ahospital based case-control study of five common SNPs, three in ERCC1(rs3212986, rs2298881and rs11615) and two in XPF (rs2276466andrs6498486).Methods：This study selected204cases of hospitalized patients withcolorectal cancer in China-Japan union hsopital of Jilin Universitybetween January2011and December2012, at the age of37-78years old; at the same time, we selected204cases of medical center in healthyvolunteers as controls, aged between32-67years of age. All of theparticipants were obtaining informed consent and signature. To analyzethe correlation of ERCC1and XPF gene polymorphisms and colorectalcancer risk, at the same time, smoking and susceptibility of correlationanalysis.Results：1. In a total of204patients with colorectal cancer patients, theaverage age was56.28±13.70years, age range37-78years old, lessthan60years old patients accounted for the number of58.82%, of which79cases of male patients,125female patients; the healthy control groupfor the number of204cases, the averageage was55.83±16.35years,age range in the32-67years old, including79cases of male, female125cases. Smoking history of patients with rectal cancer and has a closecorrelation (OR=1.54,95%CI=1.003-2.37), but no statistical differencebetween drinking history.2. ERCC1rs3212986, the distribution of rs2298881and rs11615genotypes with Hardy-Weinberg balance law of genetic equilibrium (P>0.05),common Chinese characteristics described by MAF and NCBI in the threeSNP in the dbSNP database,and three SNP MAF were greater than10%.3. The distribution of XPF rs6498486genotypes withHardy-Weinberg balance law of genetic equilibrium (P>0.05), commonChinese characteristics described by MAFand NCBI in the SNP dbSNPdatabase are similar, and the SNP MAF were greater than10%.4. Analysis showed that ERCC1rs3212986than those with the GGgenotype, the TTgenotype and T allele risk of colorectal cancerincreased slightly (95%CIs1.93(0.96-3.94) and1.49(0.95-2.13),ERCC1rs11615TT and T alleles increased risk of colorectal cancer (95%CIs1.59(0.96-2.98) and142(0.97-2.26).5. No correlation between rs2276466and rs6498486and risk ofcolorectal cancerXPF.6. The smoking history of rs3212986and rs11615polymorphismsin patients with colorectal cancer were analyzed, rs3212986TTgenotype patients at risk forsmoking and disease of colorectal cancermore closely (OR=4.09,95%CI=1.35-13.28). Rs3212986genotypepatients at risk for smoking and disease havesignificant correlation(P=0.02). While rs11615is not the case.Conclusion：Our study suggests that rs3212986and rs11615polymorphisms areassociated with risk of colorectal cancer in a Chinese Han population,rs3212986is more particularly in smokers. This finding could be usefulin revealing the genetic characteristics of colorectal cancer, and suggestsmore effective strategies for prevention and treatment. |
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