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Journal ArticleDOI

Genetic polymorphisms and head and neck cancer risk (Review).

01 May 2008-International Journal of Oncology (Int J Oncol)-Vol. 32, Iss: 5, pp 945-973
TL;DR: Examination of published data regarding the contribution of genetic polymorphisms to risk of head and neck cancer found increased risk for HNC was associated consistently with the ALDH2*1/*2, p53 codon 72 Pro/Pro and EPHX1 codon 113 Tyr/His and His/His genotypes.
Abstract: The aim of this report is to review and evaluate, in a comprehensive manner, the published data regarding the contribution of genetic polymorphisms to risk of head and neck cancer (HNC). All relevant studies available in MEDLINE and published before July 2007 were identified. Studies carried out in humans that compared HNC patients with at least 1 standard control group were considered for analysis. Two hundred and eighteen publications and 3 published meta-analyses were identified. Seventy-five (34%) studies were conducted in Asian, 72 (33%) in American, and 68 (31%) in European countries. The most widely studied gene was GSTM1 (58 studies), followed by GSTT1 (42 studies), GSTP1 (codon 105, 22 studies) and p53 (codon 72, 20 studies). GSTM1, GSTT1, GSTP1, XRCC1 codons 194 and 399, and CYP1A1 codon 462 were examined by meta-analyses, and significant relations were found between the GSTM1-null genotype and an increased risk for HNC. In addition, increased risk for HNC was associated consistently with the ALDH2*1/*2, p53 codon 72 Pro/Pro and EPHX1 codon 113 Tyr/His and His/His genotypes. Cohort studies that simultaneously consider multiple genetic and environmental factors possibly involved in carcinogenesis of the head and neck are needed to ascertain not only the relative contribution of these factors to tumor development but also the contributions of their putative interactions.

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Citations
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Journal ArticleDOI
TL;DR: New research suggests that ALDH2 dysfunction may contribute to a variety of human diseases including cardiovascular diseases, diabetes, neurodegenerative diseases, stroke, and cancer, and epidemiological studies suggest a correlation between this inactivating mutation and increased propensity for common human pathologies.
Abstract: A family of detoxifying enzymes called aldehyde dehydrogenases (ALDHs) has been a subject of recent interest, as its role in detoxifying aldehydes that accumulate through metabolism and to which we are exposed from the environment has been elucidated. Although the human genome has 19 ALDH genes, one ALDH emerges as a particularly important enzyme in a variety of human pathologies. This ALDH, ALDH2, is located in the mitochondrial matrix with much known about its role in ethanol metabolism. Less known is a new body of research to be discussed in this review, suggesting that ALDH2 dysfunction may contribute to a variety of human diseases including cardiovascular diseases, diabetes, neurodegenerative diseases, stroke, and cancer. Recent studies suggest that ALDH2 dysfunction is also associated with Fanconi anemia, pain, osteoporosis, and the process of aging. Furthermore, an ALDH2 inactivating mutation (termed ALDH2*2) is the most common single point mutation in humans, and epidemiological studies suggest a correlation between this inactivating mutation and increased propensity for common human pathologies. These data together with studies in animal models and the use of new pharmacological tools that activate ALDH2 depict a new picture related to ALDH2 as a critical health-promoting enzyme.

441 citations


Cites background from "Genetic polymorphisms and head and ..."

  • ...Reviews on many primary articles and meta-analyses consistently found ALDH2*2 as one of the most common genetic polymorphisms involved in UADT cancers (30, 119)....

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  • ...Only 40–50% of these patients survive 5 years after diagnosis, thus leading to annual deaths of 270,000 from these cancers (119, 169)....

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Journal ArticleDOI
TL;DR: The data support the role of ERCC1 as a predictive marker for therapy response for neoadjuvant radiochemotherapy in esophageal cancer patients and single-nucleotide polymorphisms of ER CC1 and XRCC1 could be applied to further individualize treatment strategies.

71 citations


Cites result from "Genetic polymorphisms and head and ..."

  • ...There are previous studies describing the predictive impact of XRCC1 Arg399Gln polymorphism for therapy response in esophageal, lung, and cervical cancer treated with platinumbased neoadjuvant therapy.21,36,28 Concerning the polymorphism A194G additionally analyzed in this study, there are so far only reports that associate this SNP with decreased risk of cancer reviewed by Goode et al.14,37,38 The present study is the first one showing an association of XRCC1 A194G with response prediction....

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  • ...Concerning the polymorphism A194G additionally analyzed in this study, there are so far only reports that associate this SNP with decreased risk of cancer reviewed by Goode et al.(14,37,38) The present study is the first one showing an association of XRCC1 A194G with response prediction....

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Journal Article
TL;DR: A review of the relationship between genetic polymorphisms involved in carcinogen metabolism, alcohol metabolism and cell-cycle control with the risk of head and neck cancer was performed in this article.
Abstract: The purpose of this report is to review the relationship between genetic polymorphisms involved in carcinogen metabolism, alcohol metabolism and cell-cycle control with the risk of head and neck cancer. The review was performed on available studies on genetic polymorphisms and head and neck cancer (HNC) published in PubMed up to September 2011. 246 primary articles and 7 meta-analyses were published. Among these, a statistically significant association was reported for glutathione S-transferases (GSTM1), glutathione S-transferases (GSTT1) and human microsomal epoxide hydrolase (EPHX1) genes. An increased risk for HNC was also associated reported for P53 codon 72 Pro/Pro, ALDH2 and three variants of the ADH gene: ADH1B (rs1229984), ADH7 (rs1573496) and ADH1C (rs698).

61 citations

Journal ArticleDOI
TL;DR: The combined Arg194Trp-Arg399Arg genotype of base excision repair gene XRCC1 that was associated with HNSCC is identified and may have an impact on identification of a high-risk cancer population.
Abstract: The genes of base excision repair (BER) pathway have been extensively studied in the association with various human cancers. We performed a case-control study to test the association between two common single nucleotide polymorphisms (SNPs) of XRCC1 gene with human head and neck squamous cell carcinoma (HNSCC). The genotype analysis of Arg194Trp and Arg399Gln gene polymorphisms for 92 HNSCC patients and 124 controls of cancer free subjects, in Polish population were performed using the PCR-based restriction fragment length polymorphism (PCR-RFLP) with endonuclease Msp I. No altered risk has been found individually for these SNPs, however haplotypes analysis showed high association with head and neck cancer. The highest frequency, according to wild-type of Arg194Arg and Arg399Arg genotypes, was identified for Arg194Trp-Arg399Arg haplotype (OR, 2.96; 95% CI, 1.01–8.80). Finally, we identified the combined Arg194Trp-Arg399Arg genotype of base excision repair gene XRCC1 that was associated with HNSCC and may have an impact on identification of a high-risk cancer population.

57 citations


Cites background from "Genetic polymorphisms and head and ..."

  • ...The polymorphisms chosen for this study have been shown to have functional significance and may be responsible for a low DNA repair capacity phenotype characteristic of cancer patients including head and neck squamous carcinomas [29-32]....

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  • ...Major studies of head and neck cancer has been focused on polymorphisms of genes encoding enzymes of xenobiotic metabolism and DNA repair [32,40]....

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Journal ArticleDOI
TL;DR: The data suggest that KLF13 and FGFR3 contribute to malignancy in oral cancer cells and may be useful biomarkers for early detection and possible targets for therapy.
Abstract: KLF13 and FGFR3 have important cellular functions and each is believed to play a role in cancer. KLF13 is a transcription factor required for the expression of several oncogenes. FGFR3 is a fibroblast growth factor receptor that initiates a signaling cascade leading to the activation of numerous cellular pathways. Here we show that KLF13 and FGFR3 are overexpressed in oral cancer cells. We also show that artificially reducing cellular levels of KLF13 and FGFR3 decreases cell proliferation and increases sensitivity to ionizing radiation. These data suggest that KLF13 and FGFR3 contribute to malignancy in oral cancer cells and may be useful biomarkers for early detection and possible targets for therapy.

51 citations


Cites background from "Genetic polymorphisms and head and ..."

  • ..., 2009], and CYP1A1 plays a role in head and neck and lung cancers [Agundez, 2004; Li et al., 2004; Hiyama et al., 2008]....

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  • ...…ovarian cancer, and oral cancer [Negus et al., 1997; Robinson et al., 2003; Mori et al., 2004; Vaday et al., 2006; Karnoub et al., 2007; Borczuk et al., 2008; Chuang et al., 2009], and CYP1A1 plays a role in head and neck and lung cancers [Agundez, 2004; Li et al., 2004; Hiyama et al., 2008]....

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References
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Journal ArticleDOI
TL;DR: A website for performing power calculations for the design of linkage and association genetic mapping studies of complex traits and the package is made available atstatgen.iop.ac.uk/gpc.
Abstract: Summary: Aw ebsite for performing power calculations for the design of linkage and association genetic mapping studies of complex traits. Availibility: The package is made available at http://

2,108 citations

Journal ArticleDOI
TL;DR: Characterization of the GSTT1 polymorphism will enable a more accurate assessment of human health risk from synthetic halomethanes and other industrial chemicals.
Abstract: In humans, glutathione-dependent conjugation of halomethanes is polymorphic, with 60% of the population classed as conjugators and 40% as non-conjugators. We report the characterization of the genetic polymorphism causing the phenotypic difference. We have isolated a cDNA that encodes a human class Theta GST (GSTT1) and which shares 82% sequence identity with rat class Theta GST5-5. From PCR and Southern blot analyses, it is shown that the GSTT1 gene is absent from 38% of the population. The presence or absence of the GSTT1 gene is coincident with the conjugator (GSST1+) and non-conjugator (GSTT1-) phenotypes respectively. The GSTT1+ phenotype can catalyse the glutathione conjugation of dichloromethane, a metabolic pathway which has been shown to be mutagenic in Salmonella typhimurium mutagenicity tester strains and is believed to be responsible for carcinogenicity of dichloromethane in the mouse. In humans, the enzyme is found in the erythrocyte and this may act as a detoxification sink. Characterization of the GSTT1 polymorphism will thus enable a more accurate assessment of human health risk from synthetic halomethanes and other industrial chemicals.

1,302 citations

Journal ArticleDOI
TL;DR: Data indicate that XRCC1, which has no known catalytic activity, might serve as a scaffold protein during base excision‐repair, allowing for more efficient ligation after filling of a single nucleotide patch.
Abstract: Repair of a uracil-guanine base pair in DNA has been reconstituted with the recombinant human proteins uracil-DNA glycosylase, apurinic/apyrimidinic endonuclease, DNA polymerase beta and DNA ligase III. The XRCC1 protein, which is known to bind DNA ligase III, is not absolutely required for the reaction but suppresses strand displacement by DNA polymerase beta, allowing for more efficient ligation after filling of a single nucleotide patch. We show that XRCC1 interacts directly with DNA polymerase beta using far Western blotting, affinity precipitation and yeast two-hybrid analyses. In addition, a complex formed between DNA polymerase beta and a double-stranded oligonucleotide containing an incised abasic site was supershifted by XRCC1 in a gel retardation assay. The region of interaction with DNA polymerase beta is located within residues 84-183 in the N-terminal half of the XRCC1 protein, whereas the C-terminal region of XRCC1 is involved in binding DNA ligase III. These data indicate that XRCC1, which has no known catalytic activity, might serve as a scaffold protein during base excision-repair. DNA strand displacement and excessive gap filling during DNA repair were observed in cell-free extracts of an XRCC1-deficient mutant cell line, in agreement with the results from the reconstituted system.

795 citations

Journal ArticleDOI
TL;DR: Both p53Arg and p53Pro are morphologically wild type and do not differ in their ability to bind to DNA in a sequence-specific manner, however, there are a number of differences between the p53 variants in their abilities to bind components of the transcriptional machinery, to activate transcription, to induce apoptosis, and to repress the transformation of primary cells.
Abstract: The wild-type p53 protein exhibits a common polymorphism at amino acid 72, resulting in either a proline residue (p53Pro) or an arginine residue (p53Arg) at this position. Despite the difference that this change makes in the primary structure of the protein resulting in a difference in migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis, no differences in the biochemical or biological characteristics of these wild-type p53 variants have been reported. We have recently shown that p53Arg is significantly more susceptible than p53Pro to the degradation induced by human papillomavirus (HPV) E6 protein. Moreover, this may result in an increased susceptibility to HPV-induced tumors in homozygous p53Arg individuals. In further investigating the characteristics of these p53 variants, we now show that both forms are morphologically wild type and do not differ in their ability to bind to DNA in a sequence-specific manner. However, there are a number of differences between the p53 variants in their abilities to bind components of the transcriptional machinery, to activate transcription, to induce apoptosis, and to repress the transformation of primary cells. These observations may have implications for the development of cancers which harbor wild-type p53 sequences and possibly for the ability of such tumors to respond to therapy, depending on their p53 genotype.

699 citations

Journal ArticleDOI
TL;DR: Comparisons of required sample sizes indicate that the family-based designs (case-sibling and case-parent) generally require fewer matched sets than the case-control design to achieve the same power for detecting a GxE interaction.
Abstract: Consideration of gene-environment (GxE) interaction is becoming increasingly important in the design of new epidemiologic studies. We present a method for computing required sample size or power to detect GxE interaction in the context of three specific designs: the standard matched case-control; the case-sibling, and the case-parent designs. The method is based on computation of the expected value of the likelihood ratio test statistic, assuming that the data will be analysed using conditional logistic regression. Comparisons of required sample sizes indicate that the family-based designs (case-sibling and case-parent) generally require fewer matched sets than the case-control design to achieve the same power for detecting a GxE interaction. The case-sibling design is most efficient when studying a dominant gene, while the case-parent design is preferred for a recessive gene. Methods are also presented for computing sample size when matched sets are obtained from a stratified population, for example, when the population consists of multiple ethnic groups. A software program that implements the method is freely available, and may be downloaded from the website http://hydra.usc.edu/gxe.

600 citations