Combinations of Genetic Data Reveal Latent Information in a Study of Oral Cancer (original) (raw)
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Combinations of genetic data in a study of oral cancer
Genes & cancer, 2015
In the single locus strategy a number of genetic variants are analyzed, in order to find variants that are distributed significantly different between controls and patients. A supplementary strategy is to analyze combinations of genetic variants. A combination that is the genetic basis for a polygenic disorder will not occur in in control persons genetically unrelated to patients, so the strategy is to analyze combinations of genetic variants present exclusively in patients. In a previous study of oral cancer and leukoplakia 325 SNPs were analyzed. This study has been supplemented with an analysis of combinations of two SNP genotypes from among the 325 SNPs. Two clusters of combinations containing 95 patient specific combinations were significantly associated with oral cancer or leukoplakia. Of 373 patients with oral cancer 205 patients had a number of these 95 combinations in their genome, whereas none of 535 control persons had any of these combinations in their genome.
Oral Oncology, 2016
Background: Oral cancers are preceded by oral potentially malignant disorders (OPMD). Understanding genetic susceptibility for OPMD risk could provide an opportunity for risk assessment of oral cancer through early disease course. We conducted a review of single nucleotide polymorphism (SNP) studies for OPMD risk. Methods: We identified all relevant studies examining associations of SNPs with OPMD (leukoplakia, erythroplakia and oral sub-mucous fibrosis) conducted worldwide between January, 2000 and February, 2016 using a combined keyword search on PubMed. Of these, 47 studies that presented results as odds ratios and 95% CI were considered for full review. Results: The majority of eligible studies that explored candidate gene associations for OPMD were small (N < 200 cases), limiting their scope to provide strong inference for any SNP identified to date in any population. Commonly studied SNPs were genes of carcinogen metabolism (n = 18 studies), DNA repair (n = 11 studies), cell cycle control (n = 8 studies), extra-cellular matrix alteration (n = 8 studies) and immune-inflammatory (n = 6 studies) pathways. Based on significant associations as reported by two or more studies, suggestive markers included SNPs in GSTM1 (null), CCND1 (G870A), MMP3 (-1171; promotor region), TNFa (-308; rs800629), XPD (codon 751) and Gemin3 (rs197412) as well as in p53 (codon 72) in Indian populations. However, an equal or greater number of studies reported null or mixed associations for SNPs in GSTM1 (null), p53 (codon 72), XPD (codon 751), XRCC (rs25487 C/T), GSTT1 (null) and CYP1A1m1 (MspI site). Conclusion: Candidate gene association studies have not yielded consistent data on risk loci for OPMD. High-throughput genotyping approaches for OPMD, with concurrent efforts for oral cancer, could prove useful in identifying robust risk-loci to help understand early disease course susceptibility for oral cancer.
The Indian journal of medical research, 2012
N-acetyltransferases 1 and 2 (NAT1 and NAT2) are important enzymes for metabolism of tobacco carcinogens. Due to polymorphisms, improper activities of these enzymes might lead to the formation of DNA adducts that may modulate risk of tobacco related oral precancer and cancer. Previously, it was shown that NAT2 polymorphisms did not modulate the risk of oral precancer and cancer. We undertook this study to check whether polymorphisms at NAT1 can modulate the risk of oral leukoplakia and cancer either alone or in combination with NAT2. Genotypes at four SNPs on NAT1 were determined by TaqMan method in 389 controls, 224 leukoplakia and 310 cancer patients. Genotype data were analyzed to know haplotypes and acetylation status of individuals and, then to estimate the risk of diseases. Using our previously published NAT2 data, combination of NAT1 and NAT2 acetylation genotypes of patients and controls were also analyzed to estimate the risk of diseases. Analysis of NAT1 genotype data reve...
GSTM1 polymorphism and oral leukoplakia
Journal of Oral Pathology and Medicine, 2006
BACKGROUND: Molecular epidemiological studies have now provided evidence that an individual susceptibility to cancer is mediated by genetic and environmental factors. Genetic polymorphisms have been described for enzymes involved in the metabolism of tobacco carcinogens and cancer risk is determined by the degree of expression and/or activity of enzymes involved in carcinogen activation or deactivation. The objective of this study was to investigate the GSTM1 null polymorphism and the risk for oral leukoplakia in individuals with tobacco-smoking habit in a Brazilian population. METHODS: A total of 52 tobacco-smoking patients with oral leukoplakia and 52 tobacco-smoking controls were recruited in a Brazilian population. The GSTM1 genotypes were studied by polymerase chain reaction-based methods. RESULTS: The frequency of the GSTM1 null genotype in the group with oral leukoplakia (57.7%) was statistically different from the controls (34.6%; OR: 2.57, 95% CI: 1.16-5.69, P < 0.05). The stratification of the samples according to the level of dysplasia showed increased prevalence of GSTM1 null genotype on lesions with moderate/severe histological dysplasia (68.2%) compared with the control group (31.9%). This difference was statistically significant (OR: 4.59, 95% CI: 1.29-16.33, P < 0.05). CONCLUSION: In conclusion, the GSTM1 null genotype may increase the risk for oral leukoplakia development.
Cancer Epidemiology Biomarkers & Prevention, 2005
An individual's susceptibility to oral precancer and cancer depends not only on tobacco exposure but also on the genotypes/haplotypes at susceptible loci. In this hospitalbased case-control study, 310 cancer patients, 197 leukoplakia patients, and 348 controls were studied to determine risk of the disease due to polymorphisms at three sites on XRCC1 and one site on XRCC3. Independently, variant genotypes on these loci did not modulate risk of leukoplakia and cancer except for the XRCC1 (codon 280) risk genotype in exclusive smokeless tobacco users with leukoplakia [odds ratios (OR), 2.4; 95% confidence intervals (CI), 1.0-5.7]. But variant haplotypes, containing one variant allele, on XRCC1 increased the risk of leukoplakia (OR, 1.3; 95% CI, 1.0-1.7). Among stratified samples, mixed tobacco users, carrying variant haplotypes, also had increased risk of both leukoplakia (OR, 2.2; 95% CI, 1.3-3.9) and cancer (OR, 1.9; 95% CI, 1.2-3.1). In a previous study on this population, it was shown that the GSTM3 (A/A) genotype increased the risk of oral leukoplakia and cancer among smokers, which has also been substantiated in this study with expanded sample sizes. The simultaneous presence of two risk genotypes in smokers, one on each of two loci, GSTM3 and XRCC1 (codon 280), increased the risk of cancer (OR, 2.4; 95% CI, 1.0-5.8). Again, smokers carrying two risk genotypes, one on each of two loci, GSTM3 and XRCC1 (codon 399), were also overrepresented in both leukoplakia and cancer populations (P trend = 0.02 and 0.04, respectively) but enhancement of risks were not observed; probably due to small sample sizes. Therefore, the presence of variant haplotypes on XRCC1 and two risk genotypes, one on each of two loci, GSTM3 and XRCC1, could be useful to determine the leukoplakias that might progress to cancer in a group of patients. (Cancer Epidemiol Biomarkers Prev
GSTT1 polymorphism and oral leukoplakia
Anticancer research
Considering that tobacco is the main etiological factor in oral cancer and that oral leukoplakia is the most prevalent potentially malignant lesion, together with the fact that GSTT1 polymorphism increases the risk of oral squamous cell carcinoma, the purpose of this study was to investigate the GSTT1 null polymorphism and the risk of oral leukoplakia in individuals with tobacco smoking habits in a Brazilian population. The GSTT1 genotypes of 72 tobacco smoking patients with oral leukoplakia and 72 tobacco smoking healthy subjects were studied by PCR-based methods. The frequency of the GSTT1 null genotype in the group with oral leukoplakia (48.6%) was statistically different from the controls (27.8%). After stratification, the frequencies of the null genotype in female patients, lesions with absent/mild grade of dysplasia and from low-risk sites were statistically different from the control. The GSTT1 null genotype may increase the risk of developing oral leukoplakia.
Cancer, 2007
BACKGROUND. Polymorphisms at mitochondrial (mt) loci could modulate the risk of diseases including cancers. Here the mtDNA polymorphisms at 12,308 nucleotide pairs (np), 11,467 np, 10,400 np, and 10,398 np were studied to examine the association with the risk of oral cancer and leukoplakia, alone and in combination with polymorphisms at the GST loci. METHODS. Polymorphisms at mt loci were screened in 310 cancer, 224 leukoplakia, and 389 control individuals by polymerase chain reaction (PCR) restriction length polymorphism (RFLP) and most of the GST genotype data were taken from previously published reports. Data were analyzed to determine the risk of the diseases. RESULTS. The major allele, A, at 12,308 np on tRNA Leu (CUN), increased the risk of cancer (odd ratio [OR] of 1.7; 95% confidence interval [95% CI], 1.1-2.6) but not that of leukoplakia. The same allele also appeared to increase the risk of cancer in smokers (OR of 4.0; 95% CI, 1.1-14.4), who are mostly males (OR of 1.8; 95% CI, 1.1-3-2), but not in smokeless tobacco users, who are mostly females. The major allele A at 11467 np demonstrated identical results as the major allele, A, at 12,308 np. The major alleles G at 10,398 np and T at 10,400 np (ie, M-haplogroup) increased the risk of cancer significantly in smokers (OR of 2.6; 95% CI, 1.2-5.7 and OR of 2.4; 95% CI, 1.1-5.1, respectively). The risk-risk genotype-allele combination at GSTP1 and mt12308 np loci increased the risk of cancer (OR of 2.6; 95% CI, 1.4-4.9) when compared with the nonrisk-nonrisk combination in leukoplakia patients. CONCLUSIONS. Polymorphisms at the mt loci alone and in combination with the risk genotype at GSTP1 increased the risk of oral cancer. Thus, risk genotypes from 2 different organelles may work in combination to increase the risk of oral cancer.
Signature of genetic associations in oral cancer
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2017
Oral cancer etiology is complex and controlled by multi-factorial events including genetic events. Candidate gene studies, genome-wide association studies, and next-generation sequencing identified various chromosomal loci to be associated with oral cancer. There is no available review that could give us the comprehensive picture of genetic loci identified to be associated with oral cancer by candidate gene studies-based, genome-wide association studies-based, and next-generation sequencing-based approaches. A systematic literature search was performed in the PubMed database to identify the loci associated with oral cancer by exclusive candidate gene studies-based, genome-wide association studies-based, and next-generation sequencing-based study approaches. The information of loci associated with oral cancer is made online through the resource "ORNATE." Next, screening of the loci validated by candidate gene studies and next-generation sequencing approach or by two indepen...
Cancer Epidemiology Biomarkers …, 2005
An individual's susceptibility to oral precancer and cancer depends not only on tobacco exposure but also on the genotypes/haplotypes at susceptible loci. In this hospitalbased case-control study, 310 cancer patients, 197 leukoplakia patients, and 348 controls were studied to determine risk of the disease due to polymorphisms at three sites on XRCC1 and one site on XRCC3. Independently, variant genotypes on these loci did not modulate risk of leukoplakia and cancer except for the XRCC1 (codon 280) risk genotype in exclusive smokeless tobacco users with leukoplakia [odds ratios (OR), 2.4; 95% confidence intervals (CI), 1.0-5.7]. But variant haplotypes, containing one variant allele, on XRCC1 increased the risk of leukoplakia (OR, 1.3; 95% CI, 1.0-1.7). Among stratified samples, mixed tobacco users, carrying variant haplotypes, also had increased risk of both leukoplakia (OR, 2.2; 95% CI, 1.3-3.9) and cancer (OR, 1.9; 95% CI, 1.2-3.1). In a previous study on this population, it was shown that the GSTM3 (A/A) genotype increased the risk of oral leukoplakia and cancer among smokers, which has also been substantiated in this study with expanded sample sizes. The simultaneous presence of two risk genotypes in smokers, one on each of two loci, GSTM3 and XRCC1 (codon 280), increased the risk of cancer (OR, 2.4; 95% CI, 1.0-5.8). Again, smokers carrying two risk genotypes, one on each of two loci, GSTM3 and XRCC1 (codon 399), were also overrepresented in both leukoplakia and cancer populations (P trend = 0.02 and 0.04, respectively) but enhancement of risks were not observed; probably due to small sample sizes. Therefore, the presence of variant haplotypes on XRCC1 and two risk genotypes, one on each of two loci, GSTM3 and XRCC1, could be useful to determine the leukoplakias that might progress to cancer in a group of patients.