CYP1A1 MspI Polymorphism and Cervical Carcinoma Risk in the Multi-Ethnic Population of Malaysia: a Case-Control Study

Background: Tobacco smoking is considered a risk factor for cervical cancer development due to the presence of tobacco based carcinogenic metabolites in cervical cells of female smokers. In this study, we investigated the role of the T3801C (MspI) polymorphism of CYP1A1, a gene encoding an enzyme necessary for the initiation of tobacco based carcinogen metabolism, on cervical cancer risk. The T to C substitution may alter CYP1A1 activities, potentially elevating cervical cancer risk. Since results of gene-disease association studies vary according to the study population, the multi-ethnic population of Malaysia provides an excellent representative cohort for identifying and comparing the cervical cancer risk among the 3 major ethnics in Southeast Asia in relation to CYP1A1 MspI polymorphism. Materials and Methods: A total of 195 Thin Prep Pap smear samples from HPV negative and cancer free females were randomly selected as controls while 106 formalin fixed paraffin embedded samples from females with invasive cervical cancer were randomly selected for the cases group. The polymorphisms were identified using restriction fragment length polymorphism (RFLP) PCR. Results: We found no significant associations between CYP1A1 MspI polymorphism and cervical cancer in the general Malaysian female population. However, upon ethnic stratification, the variant C/C genotype was significantly associated with a 4.66-fold increase in cervical cancer risk in Malay females (95% CI= 1.21 17.9; p=0.03). No significant association was observed in the Chinese and Indian females. Additionally, there were no significant associations in the dominant model and allele frequency model analysis in both the general and ethnically stratified female population of Malaysia. Conclusions: Our findings suggest that the C/C genotype of CYP1A1 MspI polymorphism is associated with the development of cervical carcinoma in the Malay females of Malaysia.     

Nucleotide Excision Repair Capacity and XPC and XPD Gene Polymorphism Modulate Colorectal Cancer Risk

Background

Colorectal cancer (CRC) is leading malignant tumors to occur mainly in industrialized countries, where it exhibits one of the highest mortality rates. Up to 80% of all CRCs characterize a chromosomal instability (CIN) phenotype. The main challenge faced by scientist is to reveal the mechanism of CIN development. An often proposed model is defects in DNA repair in terms of efficiency and genetic variations that modulate the response to stimuli from the environment. The objectives of this research were to determine whether nucleotide excision repair (NER) might affect CRC risk.

XRCC4 c.1394G>T Single Nucleotide Polymorphisms and Breast Cancer Risk among Filipinos

Background: The identification of cancer-associated single nucleotide polymorphisms (SNP) and mutationgenes is a promising approach in recognizing individuals who are at risk of developing cancer. Hence, this studywas conducted to determine the association between XRCC4 c.1394G>T SNP and breast cancer development amongFilipinos. Methods: Genotyping for XRCC4 c.1394G>T SNP was performed on breast cancer patients (n=103) andtheir age- and sex- matched clinically healthy controls (n=103) by polymerase chain reaction – restriction fragmentlength polymorphism. Results: Significant difference in genotype (p=0.007) and allele (p=0.003) frequencies in XRCC4c.1394G>T was observed between the breast cancer cases and controls. Carriers of the XRCC4 c.1394 G>T genotypewere observed to have significantly higher risk of developing breast cancer compared to individuals with T/T genotype(OR=2.67, 95% CI: 1.36 – 5.25). XRCC4 c.1394G>T combined with passive smoking may also significantly increaserisk of breast cancer (OR=14.73; 95% CI= 9.88-18.86). Conclusion: XRCC4 c. 1394G>T may be associated withbreast cancer development among Filipinos.     

A Case-Control Study of the Effectiveness of Cervical Cancer Screening in Osaka, Japan

In the small town of Nose in Osaka, Japan, a population-based screening program for cervical cancer by Papanicolaou smear has been conducted since 1965. In order to evaluate the effectiveness of screening in terms of the reduction of the mortality and the incidence of invasive cervical cancer, two types of case-control studies were carried out. In the first study, the case series consisted of all women who died of cervical cancer under 80 years of age at the time of diagnosis in 1965-1987 (N = 15). For each case, 10 controls were chosen from living residents, matched by year of birth. It showed that the odds ratio (OR) of dying of cervical cancer for screened versus non-screened women was 0.22 (95%CI = 0.03-1.95). In the second study, the case series consisted of all women who were diagnosed as having invasive cancer under 80 years of age at the time of diagnosis in the same period (N = 28). For each case, 10 controls were chosen from living residents without invasive cancer, matched by year of birth and according to whether or not they were screened at the year of the diagnosis of the matched case. It showed that the OR of getting invasive cancer for screened versus non-screened women was 0,41 (95%CI = 0.13-1.29). From these results, it was estimated that 78% of cervical cancer mortality and 59% of invasive cervical cancer incidence among non-screened women could be prevented by cervical cancer screening.     

Lack of Associations of the MDM4 rs4245739 Polymorphism with Risk of Thyroid Cancer among Iranian-Azeri Patients: a Case-Control Study

Background and Aim: MDM4, a negative regulator of the p53 tumor suppression pathway, has been demonstrated to be overexpressed in a variety of human cancers. Research has revealed that the rs4245739 A>C polymorphism of MDM4 in the 3′-untranslated region makes it a miR-191 target site, leading to lower MDM4 expression. This study aimed to detect if the rs4245739 single nucleotide polymorphism (SNP) impacts on thyroid cancer (TC) development in Iranian-Azeri patients. Materials and Method: Blood samples were taken from 232 healthy controls and 130 TC patients of Iranian-Azeri ethnicity. For genotyping, Tetra-ARMS PCR was performed. SPSS for Windows (version 22.0, IBM SPSS Inc., USA) and the SHEsis online software were used for data analysis. Results: Alleles of MDM4 rs4245739 SNP demonstrated no significant different in frequencies between patients and controls (p>0.05). Additionally, genotypes of MDM4 rs4245739 SNP did not increase or decrease TC risk in patients compared with healthy subjects. Conclusion: Considering the lack of any observed association between the MDM4 rs4245739 polymorphism and TC, we conclude no significant role in the pathophysiology of the disease.     

SNPs of Excision Repair Cross Complementing Group 5 and Gastric Cancer Risk in Chinese Populations

We conducted a case-control study to determine the association between several potential SNPs of excisionrepair cross complementing group 5 (XPG) and gastric cancer susceptibility, and roles of XPG polymorphismsin combination with H.pylori infection in determining risk of gastric cancer. In our study, we collected 337 newlydiagnosed gastric cancer cases and 347 health controls. Three SNPs of XPG, rs2296147T>C, rs2094258C>Tand rs873601G>A, were genotyped using the Taqman real-time PCR method with a 7900 HT sequence detectorsystem. H. pylori infection was diagnosed by ELISA. By multivariate logistic regression analysis, the rs2296147CC genotype was associated with a decreased risk of gastric cancer (OR=0.52, 95% CI=0.27-0.97), and rs2094258TT was associated with elevated risk (OR=2.13, 95% CI=1.22-3.35). Positive H.pylori individuals with rs2094258TT genotypes demonstrated increased risk of gastric cancer (OR=2.13, 95% CI=1.22-3.35), while rs2296147 CCwas associated with lower risk among patients with negative H.pylori (OR=0.45, 95%CI=0.22-0.89). Our findingssuggested that XPG polymorphisms might contribute to risk of gastric cancer among Chinese populations, butthe effect needs to be further validated by larger sample size studies.     

CYP2D6 and CYP2E1 Gene Polymorphisms and their Association with Cervical Cancer Susceptibility: A Hospital Based Case-Control Study from South-Western Maharashtra

Background: In last few years several studies all over the world discovered the genetic polymorphisms in different cytochrome P450 genes associated with risk of various cancers, but contradictory outcomes were evidenced in case of cervical cancer risk.  In this case-control study we aimed to see whether the polymorphism of CYP2D6 or CYP2E1 genes may or may not be associated with cervical cancer risk in women of rural Maharashtra. Methods: In this case-control study, the association of CYP2D6 and CYP2E1 gene polymorphism with cervical cancer risk was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The study was conducted with 350 clinically confirmed cervical cancer patients and 350 healthy women in a population of South-Western Maharashtra. The Odds ratio (OR) with 95% confidence interval and p-value were evaluated, where p ≤0.005 was considered as statistically significant. Results: After the analysis of SNP (rs389209) of CYP2D6 and SNPs (rs2031920, rs6413432, rs6413420) of CYP2E1, we noticed that variant allele A of CYP2E1*6 showed significant increase in cervical cancer cases (OR=4.81; 95% CI: 1.57- 14.77; p=0.005). The genotypic distribution of heterozygote G/A genotype of CYP2D6*4 showed negative association with cervical cancer development when age of cancer occurrence (OR=0.41; 95% CI: 0.27- 0.61; p<0.0001) and tobacco history (OR=0.35; 95% CI: 0.20- 0.59; p=0.0001) was considered. Conclusion: The findings from this study supported that rs6413432 SNP of CYP2E1*6 increased cervical cancer risk in the studied rural women population.     

Association of DNA Repair Genes XRCC1 and APE-1 with the Risk of Cervical Cancer in North Indian population

Backgrounds: Cervical cancer (CC) is one of the leading cause of death in women worldwide, HPV infection is the major risk factor in the disease development, 0and however other risk factor such as chemical carcinogens, genetic susceptibility and altered immune system are also a cause of the disease progression. In the light of the above statement we studied the base excision repair pathway (BER). Methods: We identified and studied the association of Single Nucleotide polymorphisms in the DNA repair genes of XRCC1 (Arg194Trp, Arg399G,) and APE-1Asp/148Glu to the susceptibility of cervical cancer (CC) in North Indian population. In our study of cases (n=102). Controls (n=109) were recruited from among women without cervical abnormalities. Genotypes were determined by PCR-CTPP method, Taking DNA from peripheral blood in a case control study. Results: A positive association was observed between the polymorphisms of XRCC1 genes, that is, in codons 194 (P=0.03, odds ratio (OR) =2.39, 95% confidence interval (CI)=5.2–1.1), 280 (P=0.01, OR=4.1, 95% CI=11.5–1.3) and 399 (P=0.01, OR=3.4, 95% CI=8.6–1.3) while APE-1 genotype GG (p=0.03,odds ratio(OR)=0.2,95% confidence interval (CI)=0.97-0.004) we observed a statistically significant protective role in developing cervical cancer. Conclusion: Our results suggested that, XRCC1 gene is an important candidate gene for susceptibility to cervical cancer. Although the sample size was small, the present study indicate a statistical association between cervical cancer and XRCC1 SNPs. Future studies are needed that may provide a better understanding of the association between gene polymorphism and cervical carcinoma risk.     

Polymorphisms of the XRCC1 and XPD Genes and Breast Cancer Risk: A Case-Control Study

The purpose of this case control study was to evaluate the role of X-ray repair cross-complementing group 1 (XRCC1) and xeroderma pigmentosum group D (XPD) genotypes as genetic indicators of susceptibility to breast cancer (BC). We analysed DNA samples from 114 breast cancer patients and 113 control subjects using polymerase chain reaction-restriction fragment length polymorphism. For the single nucleotide polymorphisms in XRCC1 exon 10 (Arg399Gln, G/A) and XPD exon 23 (Lys751Gln, A/C), no remarkable differences for genotype distribution and allele frequencies were observed between BC group and control group in the study. The genotype frequency for homozygote A/A in XPD exon 6 (Arg156Arg, C/A) were significantly different between BC and control groups (P < 0.0001, odds ratio = 2.14; 95% confidence interval 1.44-3.17). The data indicate a possible role for XPD (Arg156Arg, C/A) polymorphisms in BC susceptibility.     

Association of PON1-L55M Genetic Variation and Breast Cancer Risk: A Case-Control Trial

Background: Paraoxonase 1 (PON1), a multifactorial antioxidant enzyme, has a defensive role against oxidative stress, which is believed to contribute to cancer development. This study aimed to investigate the association of PON1-L55M functional polymorphism with breast cancer risk. Material and methods: In the experimental study, blood samples were collected from 150 healthy women controls and 150 breast cancer subjects. The L55M genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Results: Our analysis showed that the genotypes distribution is in Hardy-Weinberg equilibrium for both case and control groups. Our data revealed that there are significant associations between PON1-L55M polymorphism and breast cancer risk in homozygote (OR= 2.13, 95%CI= 1.14-4.00, p= 0.018), dominant (OR= 1.72, 95%CI= 1.07-2.76, p= 0.024), and allelic (OR= 1.55, 95%CI= 1.12-2.15, p= 0.008) models. Conclusions: Our results suggest that the PON1-L55M genetic variation could be a genetic risk factor for breast cancer risk and it could be considered as a molecular biomarker for screening of susceptible women.     

A Novel Polymorphism in BRCA2 Exon 8 and Breast Cancer Risk in South India

In India the incidence of breast cancer is on the rise and it is rapidly becoming the number one cancer infemales, pushing cervical cancer to the second spot. The contribution of BRCA2 to the development of the sporadicform of breast cancer remains undefined. To assess the role of SNPs in exon 8 of the BRCA2 gene in breastcancer development in India, a population-based study was here carried out on 107 breast cancer patients and96 controls by PCR-RFLP and DNA sequencing. T-C transitions at positions 29 bp and 44 bp in relation to thetotal sequence of exon 8 were identified. Characterization of BRCA genes is relevant in a prevention setting aswell as for the clinical management of hereditary breast cancer patients. The presently identified novel mutationin exon8 of the BRCA2 gene might have clinical significance.     

炎症相关基因多态性与子宫颈癌发病风险及治疗疗效的关系

目的 分析炎症相关基因多态性与子宫颈癌发病风险及治疗疗效的关系.方法 选取110例子宫颈癌患者作为实验组,另选取110例同期体检健康者作为对照组,分析IL-1B、IL-1RN及TNF-α等炎症相关基因的多态性,并比较其与子宫颈癌的发病风险及其治疗疗效的相关性.结果 携带IL-1B-511TT基因型、IL-1B-511CT基因型及IL-1B-511CT/TT基因型的患者发生子宫颈癌的风险较高(P<0.05);携带TNF-α-G/A基因型者子宫颈癌发病率较高(P<0.05);而携带IL-1RN变异型基因1/2与2/2的患者子宫颈癌发生率相对较低(P>0.05),以上基因多态性与子宫颈癌患者的临床疗效无明显相关性.结论 IL-1B-511TT、IL-1B-511CT、IL-1B-511CT/TT及TNF-α-G/A等炎症相关基因的多态性可能提高子宫颈癌的发病率,而IL-1RN变异型基因1/2与2/2可能会降低子宫颈癌的发病率,炎症相关基因多态性与子宫颈癌的临床治疗效果不相关.     

Association between Microrna 146a and Microrna 196a2 Genes Polymorphism and Breast Cancer Risk in North Indian Women

Background: Micro RNAs (miRNAs) are small, noncoding RNA molecules. They can function as either oncogenes or tumor suppressor genes. Single nucleotide polymorphisms (SNP) present in the pre-miRNA region could affect the processing of miRNA and thus alter mature miRNA expression. The studies done so far had shown conflicting results regarding association of two common polymorphisms i.e.hsa-miR-146 rs2910164 and hsa-miR-196a2 rs11614913 with breast cancer. OBJECTIVE: In the study, we examined the hsa-miR-146 rs2910164 and hsa-miR-196a2 rs11614913 SNP association with breast cancer patients in north Indian women. Materials and Methods: This study included 100 breast cancer patients and 100 controls and was done over a period of two years. Genotypes of the hsa-miR-146 (rs2910164 G>C) and hsa-miR-196a2 (rs11614913 C>T) were identified by polymerase chain reaction – restriction length polymorphism (PCR-RFLP) technique in peripheral blood DNA samples. Statistical analysis: We assessed the strength of association of miRNA polymorphisms with breast cancer using Odds ratio (OR) along with 95% confidence intervals. Results: Heterozygous genotypes of hsa-miR-196a2 rs11614913 and combined hsa-miR-146 rs2910164 & hsa-miR-196a2 polymorphism were associated with significantly increased risk of breast cancer (OR-1.7, 95% CI–1.00-3.18) and (OR-1.9, 95% CI-0.85-4.46) respectively. Conclusion: Our study suggests that rs2910164 GC and rs11614913 CT genotypes may contribute to breast cancer susceptibility in north Indian women.     

XRCC3 Thr241Met Gene Polymorphism and Risk of Colorectal Cancer in Kashmir: a Case Control Study

XRCC (X-ray cross-complementing group) genes contribute to important DNA repair mechanisms thatplay roles in the repair of single strand breaks (SSBs) induced by a variety of external and internal factors,including ionizing radiation, alkylating agents and reactive oxygen species. These repair genes have a pivotalrole in maintaining genomic stability through different pathways of base excision repair (BER). The aim of thisstudy was to investigate the XRCC3 Thr241Met gene polymorphism in colorectal cancer (CRC) in Kashmir. Weinvestigated the genotype distribution of XRCC3 gene in 120 CRC cases in comparison with 150 healthy subjectsand found a significant association between XRCC3 genotypes and CRC (p≤0.05). Both heterozygous genotype(Thr/Met) as well as homozygous variant genotype (Met/Met) were moderately associated with elevated riskof CRC [OR=2.53; OR=2.29 respectively]. Also, Thr/Met and Met/Met genotypes demonstrated a significantassociation with the risk of CRC (p = 0.003). This study displayed a significantly elevated risk for CRC inindividuals with XRCC3 Thr/Met and Met/Met Genotype of about 2.5 times that with the Thr/Thr wild genotype.     

Urinary Bladder Cancer Risk Factors: A Lebanese Case-Control Study

Background: Bladder cancer is the second most incident malignancy among Lebanese men. The purposeof this study was to investigate potential risk factors associated with this observed high incidence. Methods: Acase-control study (54 cases and 105 hospital-based controls) was conducted in two major hospitals in Beirut.Cases were randomly selected from patients diagnosed in the period of 2002-2008. Controls were convenientlyselected from the same settings. Data were collected using interview questionnaire and blood analysis. Exposuredata were collected using a structured face-to-face interview questionnaire. Blood samples were collected todetermine N-acetyltransferase1 (NAT1) genotype by PCR-RFLP. Analyses revolved around univariate, bivariateand multivariate logistic regression, along with checks for effect modification. Results: The odds of havingbladder cancer among smokers was 1.02 times significantly higher in cases vs. controls. The odds of exposure tooccupational diesel or fuel combustion fumes were 4.1 times significantly higher in cases vs controls. The oddsof prostate-related morbidity were 5.6 times significantly higher in cases vs controls. Cases and controls showeddifferent clustering patterns of NAT1 alleles. No significant differences between cases and controls were foundfor consumption of alcohol, coffee, tea, or artificial sweeteners. Conclusions: This is the first case-control studyinvestigating bladder cancer risk factors in the Lebanese context. Results confirmed established risk factorsin the literature, particularly smoking and occupational exposure to diesel. The herein observed associationsshould be used to develop appropriate prevention policies and intervention strategies, in order to control thisalarming disease in Lebanon.     

MMP1 rs1799750 Single Nucleotide Polymorphism and Lung Cancer Risk: A Meta-analysis

Background: Numerous studies have investigated the association of matrix metalloproteinase 1 (MMP1) rs1799750 single nucleotide polymorphism with lung cancer susceptibility, but the findings are inconsistent.Therefore, we performed a meta-analysis to comprehensively evaluate any possible association. Methods: We searched publications from MEDLINE, EMBASE and CNKI databases which assessed links between theMMP1 rs1799750 polymorphism and lung cancer risk. We calculated the pooled odds ratio (OR) and its 95% confidence interval (95%CI) using either fixed-effects or random-effects models. Results: The meta-analysis was based on 9 publications encompassing 4,823 cases and 4,298 controls. The overall results suggested there was a significant association between the MMP1 rs1799750 polymorphism and lung cancer risk (1G vs. 2G: OR = 0.83,95%CI = 0.73-0.94; 1G1G vs. 2G2G: OR = 0.73, 95%CI = 0.59-0.92; 1G1G vs. 1G2G/2G2G: OR = 0.87, 95%CI = 0.79-0.97; 1G1G/1G2G vs. 2G2G: OR = 0.78, 95%CI = 0.64-0.95). In the subgroup analysis by ethnicity, the association was still obvious in Asians (all P values < 0.05), but there was no association in Caucasians (all P values > 0.05). Conclusions: The MMP1 rs1799750 polymorphism is associated with decreased lung cancer risk,and a race-specific effect may exist in this association.     

Pathway-Affecting Single Nucleotide Polymorphisms (SNPs) in RPS6KA1 and MBIP Genes are Associated with Breast Cancer Risk

Background: Genetic mutations and polymorphisms play an important role in the transformation of primary cells to malignant cells as it may lead to disturbance of vital pathways regulating cell cycle, DNA damage repair, and apoptosis. In this study, we genotyped single nucleotide polymorphisms (SNPs) which were predicted to affect certain pathways and to increase the risk of breast cancer. Methods: The study included 81 Saudi breast cancer patients and 100 matching healthy controls from the Eastern Province in Saudi Arabia. The following SNPs (rs3168891, rs2899849, rs2230394, rs2229714) were then genotyped by TaqMan genotyping assay and the allele and genotype distribution was compared. Results: The minor allele frequency of the following SNPs (rs3168891, rs2899849, rs2230394, rs2229714) was T=0.17, A=0.28, A=0.22, and G=0.16 respectively. The G allele of the SNP rs3168891 was significantly associated with increased breast cancer risk (P = 0.00001) while the T allele of the same locus was associated with reduced risk of breast cancer in both heterozygous and homozygous states. The T allele of SNP rs2229714 which is located in the RPS6KA1 gene was also significantly associated with the increased risk of breast cancer. However, the rs2899849 SNP located in the Integrin beta-1 (ITGB1) gene was not associated with the increased risk of breast cancer in our study population. Haplotype analysis revealed the presence of three risk haplotypes that increases the risk of breast cancer (TGGT, TGTA, GATA). Conclusion: We showed that three, previously untested, SNPs are associated with increased risk of breast cancer in our population.  This may be added to the list of factors involved in breast cancer risk assessment studies. The benefit and the utility of the in-silico prediction of disease risk factors and their genetic association had been demonstrated in this study, yet the predicted risk alleles have to be tested in clinical studies.     

宫颈癌局部化疗+ 放疗的临床与病理研究

 目的　提高宫颈癌对放射线的敏感性 ,改善晚期患者的生存率。方法　对 5 4例晚期宫颈癌采用小剂量顺铂宫颈局部化疗加放疗 ,对照组 5 2例常规放疗。观察临床疗效、组织学改变。结果　放疗达总量 1 /7及 1 /2时 ,二组肿瘤消除 ,均有显著性差异 ( P<0 .0 1 )。组织学观察局部化疗前后有显著性变化 ,癌组织明显坏死 ,癌细胞变性坏死 ,凋亡细胞增多、组织学分级提高等。结论　小剂量顺铂宫颈局部化疗是一种理想的放射增敏剂及其方法 ,为晚期宫颈癌患者的预后带来新的希望。     

Methionine Synthase Reductase-A66G and -C524T Single Nucleotide Polymorphisms and Prostate Cancer: A Case-Control Trial

Purpose: Some variations in the sequence of methionine synthase reductase (MTRR) gene can increase the risk ofvarious cancers such as prostate cancer. The aim of this study was to investigate the association between prostate cancerand the MTRR A66G and C524T gene single nucleotide polymorphisms (SNPs) using an in silico analysis. Methods:In this case-control study, 218 Iranian men, including 108 men with prostate cancer and 110 prostate cancer-free men,were enrolled. The MTRR A66G and C524T genotyping was performed by PCR-RFLP. Some of the bioinformaticstools were employed for the evaluation of polymorphism on the molecular aspects of the MTRR. Results: With regardto the MTRR A66G polymorphism, the genotype AG (OR: 0.85, 95% CI: 0.47-1.54, p= 0.6014), genotype GG (OR:0.89, 95% CI: 0.42-1.87, p= 0.7512), and allele G (OR: 0.92, 95% CI: 0.63-1.35, p= 0.6686) were not associated withprostate cancer risk. However, the data for C524T SNP showed that the genotype CT was associated with prostatecancer risk (OR: 1.92, 95% CI: 1.06-3.47, p= 0.0308). Further, carriers of the allele T (OR: 1.80, 95% CI: 1.04-3.13,p= 0.0358) were associated with high risk of prostate cancer. In addition, bioinformatics analysis revealed that C524TSNP could affect some molecular aspects of the protein structure, while having no effect on the mRNA structure.Conclusion: The MTRR C524T is a genetic risk factor for prostate cancer; however, the MTRR A66G is not suggestedas a suitable biomarker for prostate cancer. To obtain more reliable results, further studies are recommended to uselarger sample sizes and investigate the effects of environmental factors.     

Risk Modulation of Oral Pre Cancer and Cancer with Polymorphisms in XPD and XPG Genes in North Indian Population

Background: Environmental carcinogens cause DNA damages which if not repaired properly, may increase therisk of cancer. The Xerodermapigmentosum group D (XPD) and group G (XPG) genes are essential genes for DNArepair and alteration in DNA repair causes cancer. The present study aimed to evaluate the relationship between XPDand XPG polymorphisms and risk of oral pre cancer and cancer. Methods: Present study genotyped 302 samples oforal diseases and 300 controls for XPD (A/C) and XPG (G/C) polymorphisms with PCR-RFLP method. Results: Ourresult showed that compared to AA genotype frequency of AC and CC genotype for XPD(A/C) polymorphism weresignificantly lower among cases than in control and are associated with decreased risk of oral diseases (OR= 0.621and 0.603 respectively). In contrast with reference to GG genotype the frequency of CC genotype of XPG (G/C) wassignificantly higher in case than in control population (p value=0.004) and found to increase the risk of oral diseases(OR= 2.077). Particularly C allele for XPD A/C polymorphism was found to be associated with decreased risk of Lichenplanus and increased risk of ( OR = 0.470 and 1.541 respectively) oral cancer. While C allele of XPG G/C polymorphismsignificantly increased the risk of Oral Submucous Fibrosis and Leukoplakia (OR= 1.879 and 1.837 respectively) butnot of Lichen planus and oral cancer. In combined genotype analysis from the aforesaid polymorphisms presence of Callele for XPD (A/C) polymorphisms were found to decrease the risk of oral diseases. However, the same C allele wasobserved to increase the chance of having high stage disease (OR= 5.71) with nodal involvement (OR= 6.78) once thecancer been initiated. Conclusion: This work shows association of XPD (A/C), XPG (G/C) polymorphisms with thedevelopment of pre oral cancer as well as oral cancer and its clinical courses.