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Biomedical subjects

R C Strange

Publications and source records attributed to R C Strange.

At least 73 records · Page 4Linked to original sources
PubMed1999

The melanocyte stimulating hormone receptor polymorphism: association of the V92M and A294H alleles with basal cell carcinoma.

Allelic variants in the melanocyte stimulating hormone receptor (MC1R) gene are susceptibility/outcome candidates for cutaneous basal cell carcinoma (BCC). We identified the val92met (V92M) and asp294his (A294H) alleles in 311 cases and 190 controls. The cases included four homo- and 53 heterozygotes for V92M and 12 heterozygotes for A294H and two compound heterozygotes (V92M/A294H). Allele frequencies were similar in controls. In the cases, we found no association between the alleles and skin type though A294H was more common in those with red hair (4/19) than with other hair colours (6/163) (P = 0.012). V92M was not associated with BCC numbers. Cases with A294H had fewer BCC in comparison with those without the allele though the difference was not significant. After inclusion of red hair in the model, A294H was significantly associated with fewer tumours. While MCIR alleles are attractive candidates for BCC, the variants studied did not influence susceptibility. The association with outcome was relatively weak. The large number of MC1R alleles and their low frequency, make assessment of the importance of this gene in the pathogenesis of skin cancers difficult.

Alleles↗
PubMed1999

Expression and subcellular localization of cyclin D1 protein in epithelial ovarian tumour cells.

The expression of cyclin D1 protein in tumour sections from 81 patients with epithelial ovarian cancer was analysed using immunohistochemistry. The tumours that overexpressed cyclin D1 in more than 10% of neoplastic cells were considered positive. Thus overexpression of cyclin D1 was observed in 72/81 (89%) of the cases examined. Protein was detected in both the nucleus and the cytoplasm in 24/81 (30%) and localized exclusively in the cytoplasm in 48/81 (59%) of the tumours. Cyclin D1 was overexpressed in both borderline and invasive tumours. There was no association between protein overexpression and tumour stage and differentiation. Furthermore, no correlation between cyclin D1 expression and clinical outcome was observed. However, in tumours overexpressing cyclin D1 (n = 72), the proportion displaying exclusively cytoplasmic localization of protein was higher in those with serous compared with non-serous histology (P = 0.004, odds ratio 4.8, 95% confidence interval 1.4-19.1). Western analysis using a monoclonal antibody to cyclin D1 identified a 36 kDa protein in homogenates from seven tumours displaying cytoplasmic only and one tumour demonstrating both nuclear and cytoplasmic immunostaining. Using restriction fragment length polymorphism polymerase chain reaction and PCR-multiplex analysis, amplification of the cyclin D1 gene (CCND1 was detected in 1/29 of the tumours demonstrating overexpression of cyclin D1 protein. We conclude that deregulation of CCND1 expression leading to both cytoplasmic and nuclear protein localization is a frequent event in ovarian cancer and occurs mainly in the absence of gene amplification.

Blotting, Western↗
PubMed1999

Multiple basal cell carcinomas in a patient with acute myeloid leukaemia and chronic lymphocytic leukaemia.

Skin cancer is a well-recognized risk of prolonged immunosuppression, for example, following renal transplantation. These tumours contrast with idiopathic lesions in that squamous cell, rather than basal cell carcinomas usually predominate. We report a Caucasian female who developed multiple basal cell carcinomas following protracted cytotoxic therapy for acute myeloid leukaemia and subsequently chronic lymphocytic leukaemia. No other clinical risk factors nor relevant polymorphisms of genes encoding for detoxifying enzymes were identified. Immune suppression is a well-recognized cause of multiple skin tumours, the most striking increase usually being of squamous cell carcinomas. We believe this woman is representative of a subgroup of immunosuppressed patients who, for as yet poorly understood reasons, have a predisposition to basal cell, rather than squamous cell carcinoma accrual.

Acute Disease↗
PubMed1999

[Genetic predisposition for the development of head and neck carcinomas].

BACKGROUND: While cigarette smoking and chronic alcohol consumption are the major risk factors for the development of head and neck cancer, it is assumed that genetic factors contribute to risk. Glutathione-S-transferase GSTM1 AB, GSTM3 BB and GSTP1 AA as well as TNF genotypes were determined from leucocyte DNA in 392 patients with head and neck carcinoma and 216 controls, with added immunohistochemical studies. Comparative genomic hybridization was used to screen for genetic alterations in the tumor tissue. RESULTS: While the frequency of GSTM1 AB was significantly lower in all head and neck carcinomas compared with controls, GSTM3 BB was significantly lower in the laryngeal and GSTP1 AA in the oral cavity/pharyngeal carcinoma cases; the frequency of the TNFb3 allele was higher in the laryngeal cases. Chromosomal alterations were specific for head and neck carcinomas, differing both in well differentiated and undifferentiated and in metastasizing and non-metastasizing tumors. CONCLUSIONS: Allelism at GST gene loci mediates susceptibility to head and neck carcinomas: GSTM1 AB is associated with a lower risk for all head and neck carcinomas, GSTM3 BB only for laryngeal carcinomas and GSTP1 AA only for oral cavity/pharyngeal carcinomas. The TNFb3 allele was significantly more frequent in laryngeal cancer patients. The genetic alterations in the tumor tissue are in line with the "tumor progression model". Genetic conditions are important from the first exposure with carcinogens up to late genetic events in the tumor tissue.

Alcohol Drinking↗
PubMed1999

[Immunohistologic and molecular genetic studies of the effect of glutathione-S-transferases on the development of squamous epithelial carcinomas in the area of the head-neck].

BACKGROUND: While cigarette smoking and alcohol consumption are the major risk factors for the development of head and neck carcinomas, it is assumed that genetic factors contribute to risk. The aim of this study was to characterize the influence of the carcinogen metabolizing glutathione-S-transferases on susceptibility to head and neck carcinomas. PATIENTS AND METHODS: Polymorphisms at GSTM1, M3, T1 and P1 gene loci were determined in 398 head and neck cancer patients and 216 controls using polymerase chain reaction and restriction enzyme digestion. The epithelial distribution of the GSTs was determined by immunohistochemical methods. RESULTS: The GSTM1 A/B genotype was less frequent in all tumor groups compared with controls. The GSTM3 B/B genotype was reduced only in the laryngeal cancer group whereas GSTP1 A/A showed significant differences between pharyngeal cancer patients and controls. Accordingly, GSTM3 was expressed only in the cilia of the laryngeal respiratory epithelium. In contrast, GSTP1 was distributed throughout all outer layers of the squamous cell epithelium. CONCLUSIONS: While GSTM1 seems to influence susceptibility to all head and neck cancers, GSTM3 and P1 reflected site-specific differences. Thus GSTM3 appears to be associated with altered risk only to laryngeal cancer whereas GSTP1 is likely to influence pharyngeal cancer risk.

Adult↗
PubMed1999

Association of NAD(P)H:quinone oxidoreductase (NQO1) null with numbers of basal cell carcinomas: use of a multivariate model to rank the relative importance of this polymorphism and those at other relevant loci.

Glutathione S-transferase GSTM1 B and GSTT1 null, and cytochrome P450 CYP2D6 EM have been associated with cutaneous basal cell carcinoma (BCC) numbers, although their quantitative effects show that predisposition to many BCC is determined by an unknown number of further loci. We speculate that other loci that determine response to oxidative stress, such as NAD(H):quinone oxidoreductase (NQO1) are candidates. Accordingly, we assessed the association between NQO1 null and BCC numbers primarily to rank NQO1 null in a model that included genotypes already associated with BCC numbers. We found that only 14 out of 457 cases (3.1%) were NQO1 null. This frequency did not increase in cases with characteristics linked with BCC numbers including gender, skin type, a truncal lesion or more than one new BCC at any presentation (MPP). However, the mean number of BCC in NQO1*0 homozygotes was greater than in wild-type allele homozygotes and heterozygotes, although the difference was not quite significant (P = 0.06). These data reflect the link between NQO1 null and BCC numbers in the 42 MPP cases rather than the whole case group. We identified an interaction between NQO1 null and GSTT1 null that was associated with more BCC (P = 0.04), although only four cases had this combination. The relative influence of NQO1 null was studied in a multivariate model that included: (i) 241 patients in whom GSTM1 B, GSTT1 null and CYP2D6 EM genotype data were available, and (ii) 101 patients in whom these genotypes, as well as data on GSTM3, CYP1A1 and melanocyte-stimulating hormone receptor (MC1R) genotypes were available. NQO1 null (P = 0.001) and MC1R asp294/asp294 (P = 0.03) were linked with BCC numbers, and the association with CYP2D6 EM approached significance (P = 0.08). In a stepwise regression model only these genotypes were significantly associated with BCC numbers with NQO1 null being the most powerful predictor.

Age Factors↗
PubMed1999

The therapeutic response to D-penicillamine in rheumatoid arthritis: influence of glutathione S-transferase polymorphisms.

OBJECTIVES: To investigate whether the therapeutic response of rheumatoid arthritis (RA) patients to D-penicillamine is associated with polymorphisms in genes of the glutathione S-transferase (GST) supergene family. METHODS: Disease activity in 81 patients with RA treated with D-penicillamine monotherapy was assessed using the Stoke Index, a validated index of disease activity, prior to treatment and at 6 months. GST typing was performed using a polymerase chain reaction-based approach and a logistic regression model was used to investigate any possible association between the therapeutic response to D-penicillamine and the GST genotype. RESULTS: A poor therapeutic response was associated with the GSTM1 null genotype [odds ratio (OR) 3.94], and in particular with the GSTM1*0/GSTM3*A haplotype (OR 7.63). CONCLUSIONS: Our results suggest that GST polymorphisms may influence the response to D-penicillamine in RA, and that patients in possession of the GSTM1*0/GSTM3*A haplotype are significantly less likely to show a beneficial response to the drug.

Antirheumatic Agents↗
PubMed1999

Association of polymorphism in glutathione S-transferase loci with susceptibility and outcome in rheumatoid arthritis: comparison with the shared epitope.

OBJECTIVE: To determine whether glutathione S-transferase GSTM1, GSTM3, GSTT1, and GSTP1 genotypes influence susceptibility or outcome in rheumatoid arthritis (RA). METHODS: 277 RA patients were compared with 577 controls to examine any associations between GST genotypes and susceptibility to RA. The effect of genotypes on outcome (Larsen and functional scores) and time integrated acute phase responses (erythrocyte sedimentation rate and C reactive protein) was assessed in 122 patients with disease duration of 5-10 years. GST and HLA-DRB1 genotypes were determined using polymerase chain reaction based assays. Data were analysed using multiple regression analysis with correction for age, sex, disease duration, and the DRB1 associated shared epitope (SE) and rheumatoid factor (RF) positivity where appropriate. RESULTS: The GSTM1*A/*B genotype was less common in RA cases (3 of 276) than in controls (22 of 591) (exact p = 0.047), though significance was lost when adjustment was made for multiple comparisons. The Larsen score was higher (p = 0.039) in the GSTM1 null patients (89.9) than those with other GSTM1 genotypes (74.7), and this was independent of the SE. Again, correction for multiple testing resulted in loss of significance. The difference in Larsen scores between patients homozygous or negative for the SE (87.9 v 74.3) was similar to that between GSTM1 null and non-null patients. No associations between GSTM3 or GSTT1 genotypes and disease markers were identified although the association between GSTP1*B/*B and Larsen score approached significance (p = 0.096). CONCLUSION: It is proposed that certain GSTs may influence susceptibility and radiological progression in RA and that this is independent of the effect of the HLA-DRB1 associated SE. The mechanism for this effect is presumed to be because of differences in the ability of various GST enzymes to utilise the cytotoxic products of oxidant stress. Although significance was lost after correction for multiple testing, the data indicate that further studies may be of value in RA to determine the influence of the GST and other genes involved in cellular protection against oxidative stress.

Acute-Phase Reaction↗
PubMed1999

Cytochrome P450 CYP2D6 genotypes: association with hair colour, Breslow thickness and melanocyte stimulating hormone receptor alleles in patients with malignant melanoma.

We previously identified associations between polymorphism in the cytochrome P450 CYP2D6 gene and outcome in several cancers. We have now examined the hypothesis that homozygosity for the mutant alleles, CYP2D6*4 and CYP2D6*3, is associated with susceptibility and outcome in malignant melanoma. Outcome was assessed by Breslow thickness. We first confirmed previous reports that these mutant alleles are associated with increased susceptibility to malignant melanoma. For example, the frequency of homozygosity for CYP2D6*4 was significantly greater (P = 0.006, chi-squared 1 d.f. = 7.4, odds ratio 2.2, 95% confidence interval 1.2, 3.9) in cases (9.1%) than in control individuals (4.3%). The frequency of homozygosity for the mutant alleles was next examined in the malignant melanoma cases grouped on the basis of characteristics associated with malignant melanoma risk. Homozygosity was significantly more common (P = 0.038) in cases with red/blonde hair than in those with brown/black hair. We found no associations between the CYP2D6 genotype and sex, skin type or eye colour. The possible association of CYP2D6 with outcome was assessed by comparing genotype frequencies in patients with tumours of Breslow thickness < 1.5 mm with those whose tumours were > or = 1.5 mm. In patients with red/blonde, but not brown or black hair, homozygosity for CYP2D6*4 was significantly associated with thicker lesions in a multivariate model (P = 0.036). We further examined the association of CYP2D6*4 homozygosity with red/blonde hair by classifying patients on the basis of homo- or heterozygosity for wild-type or val92met, asp294his or asp84glu melanocyte stimulating hormone receptor (MC1R) alleles. None of the nine patients with brown/black hair with the asp294his allele were homozygotes for CYP2D6*4. By contrast, in the patients with red/blonde hair, three of five cases with asp294his were homozygotes for the mutant CYP2D6 allele. The difference in the frequency of CYP2D6*4 homozygotes in the red/blonde cases with wild-type MC1R alleles compared with those with asp294his was significant (exact P = 0.029). No associations between val92his or asp84glu and CYP2D6 alleles were identified.

Cytochrome P-450 CYP2D6↗
PubMed1999

The glutathione S-transferases: influence of polymorphism on cancer susceptibility.

The glutathione S-transferase supergene family is an important part of cellular enzymic defence against endogenous and exogenous chemicals, many of which have a carcinogenic potential. However, while a wide variety of chemicals can act as substrates for different members of the supergene family, the precise function of these enzymes remains unclear. The supergene family comprises several gene families that include polymorphic loci, prompting the hypothesis that allelic variants associated with less effective detoxification of potential carcinogens can confer an increased susceptibility to cancer. For example, the null genotypes at the mu class GSTM1 and theta class GSTT1 loci have attracted particular interest, and recently identified allelic variants at the mu class GSTM3 and pi class GSTP1 loci are also putative susceptibility candidates. However, while associations between GSTM1 and GSTT1 genotypes and risk have been observed in some case-control studies in lung, bladder and colon cancers, other studies have reported contrary findings, and the importance of these polymorphisms in mediating the risk of smoking-related cancers remains generally unproven. We describe the influence of glutathione S-transferase polymorphisms on the risk of several cancers, including basal cell carcinoma of skin. In the latter cancer, associations between tumour numbers, site and accrual have been observed, suggesting a role for GST enzymes in the detoxification of the products of ultraviolet radiation-induced oxidative stress. We review below current knowledge of polymorphism in GST loci, possible in vivo GST substrates, and the difficulties of determining the role of this complex gene family on the basis of available epidemiological data.

Alleles↗
PubMed1999

Cyclin D1, glutathione S-transferase, and cytochrome P450 genotypes and outcome in patients with upper aerodigestive tract cancers: assessment of the importance of individual genes using multivariate analysis.

GST, CYP, and CCND1 genotypes have been associated with outcome in several cancers. Accordingly, we have examined, in patients with one squamous cell carcinoma (SCC) of the head and neck, associations between GSTM1, GSTT1, GSTM3, GSTP1, CYP2D6, CYP1A1, CYP2E1, and CCND1 genotypes and the outcome parameters, tumor extension, histological grade, and presence of nodes. We used logistic regression to study, first, each gene individually and, second, in a step-wise model that included all of the genes. Different genes were associated with each outcome parameter. Thus, GSTT1 null was associated with T3/T4 lesions in the oral cavity/pharyngeal (P = 0.029), but not laryngeal, SCC cases. GSTT1 null was also associated with histological differentiation (G3) in the oral cavity/pharyngeal, but not laryngeal, SCC cases, although this association only approached significance (P = 0.069). CCND1 GG was associated with G3 tumors in the oral cavity/pharyngeal (P = 0.011), but not laryngeal, SCC cases. The combination of GSTT1 null/CCND1 GG was also associated with G3 tumors. CYP2D6 PM and HET were associated with lymph node involvement in the laryngeal, but not oral/pharynx, SCC cases. Genes that were individually associated with outcome were also associated with the parameter in the step-wise routine. The GSTT1 null frequency was greater in 39 patients with second primary tumors than in those with one lesion (P = 0.014). The data demonstrate site-dependent associations between GSTT1 null, CCND1 GG, and CYP2D6 PM and tumor extension, differentiation, and nodes.

Carcinoma, Squamous Cell↗
PubMed1999

Presentation with multiple cutaneous basal cell carcinomas: association of glutathione S-transferase and cytochrome P450 genotypes with clinical phenotype.

We previously reported associations between numbers of basal cell carcinomas (BCCs) and glutathione S-transferase (GSTM1 and GSTT1) and cytochrome P450 (CYP2D6) genotypes. Thus, although GSTM1 AB is protective, GSTM1 null, GSTT1 null, and CYP2D6 EM are associated with increased numbers of lesions. Here, we examine the hypothesis that these genotypes are associated with high-risk subgroups. The subgroup studied comprised 119 patients with more than one previously unidentified BCC at first or later presentations [multiple presentation phenotype (MPP)]. These patients were part of a group of 773 BCC patients that also included 567 patients with one BCC and 87 patients with only one lesion at each presentation [single presentation phenotype (SPP)] but who developed multiple BCCs. The number of tumors in the MPP was significantly greater than that in the SPP groups. In the MPP but not SPP patients, GSTM1 AB, GSTT1 null, and CYP2D6 EM were significantly associated with BCC numbers, suggesting that previously observed associations reflect the influence of these genes only in the MPP cases. There was no evidence that MPP patients had received more UV exposure. We also determined whether the increased numbers of BCC in the MPP cases reflects an association with the truncal tumor phenotype. The values of the rate ratios indicated that the MPP is a marker for the risk of many BCCs, although the combination of MPP and a truncal tumor is a higher-risk phenotype. The data demonstrate the heterogeneity in BCC patients, which reflects differences in genetic factors that determine skin response to UV.

Adult↗
PubMed1998

Glutathione S-transferase polymorphisms: influence on susceptibility to cancer.

The glutathione S-transferase supergene family includes several loci that demonstrate well characterised polymorphisms. The apparently critical role of these enzymes in cellular protection from the cytotoxic and mutagenic effects of electrophiles suggest that alleles associated with impaired detoxification will confer an increased susceptibility to a wide range of diseases. This hypothesis has been examined in case control studies and while data in some diseases such as lung cancer are conflicting, an increasing body of evidence suggests the importance of several glutathione S-transferase polymorphisms. In particular, GST genotypes have been associated with an increased susceptibility or worse outcome in diseases associated with oxidative stress. For example, both GSTM1 and GSTT1 genotypes are associated with susceptibility and outcome in cutaneous basal cell carcinoma. It still remains unclear however, why particular glutathione S-transferase loci are associated with altered risk in some diseases but not others. Further, the true in vivo substrates of these enzymes is unknown, consequently their mechanism of action remains unclear.

Alleles↗
PubMed1998

Polymorphism in glutathione S-transferase loci as a risk factor for common cancers.

Though a developing body of data indicates polymorphism at GST genes influences cancer susceptibility, it is unclear why a genotype is associated with one cancer but not another. We believe the GST exert a critical role in normal cell house-keeping activities. GSTM1, GSTM3 and GSTT1 influence tumorigenesis because these enzymes utilise the products of UV-induced oxidative stress. Further support for the importance of these genes in the protection of skin from UV comes from studies in systemic lupus erythematosus (Ollier et al, 1996). Thus, GSTM1 null is associated with increased anti-Ro (but not anti-La) antibodies, a phenotype associated with photosensitivity. At present there is no basis for predicting which cancers will be influenced by GST polymorphisms though other studies do indicate that the GSTs are critical in the metabolism of environmental carcinogens. For example, GSTT1 null confers an increased risk of astrocytoma (Hand et al, 1996). While brain tumours are not clearly associated with environmental pollutants, N-methyl-N-nitrosourea, processed meats and occupation have been implicated. Why GSTT1 but not GSTM1 or GSTM3 influences the risk of astrocytoma is unclear. GSTM3 appears a good susceptibility candidate, as some astrocytes demonstrate strong expression (Hand et al, 1996). Susceptibility to squamous cell cancer of the larynx, a pathology associated with chronic consumption of tobacco and alcohol, is also influenced by allelism at GSTM3 (Jahnke et al, 1996). The roles of CYP2D6 and CYP1A1 are even more unclear, though the finding that systemic agents such as arsenic predispose to multiple BCC, suggests that CYP2D6-mediated hepatic detoxification of photosensitizing agents may be important. Importantly, the extent of altered risk conferred by genotypes is generally 2-3 fold and it is necessary to identify which other genes interact with the GST so that haplotypes associated with 10-20 fold increases in risk can be defined.

Basal Cell Carcinoma↗
PubMed1998

Susceptibility to melanoma: influence of skin type and polymorphism in the melanocyte stimulating hormone receptor gene.

Allelic variation at the melanocyte stimulating hormone receptor (MC1R) gene has been linked with sun-sensitive skin types, suggesting it is a susceptibility candidate for melanoma. We determined the frequency of the val92met, asp294his, and asp84glu MC1R alleles in 190 Caucasian controls and 306 melanoma cases and studied their association with skin type and hair color. The percentage of controls with at least one val92met, asp294his, or asp84glu allele was 17.3%, 6.8%, and 3.5%, respectively. Individually, frequencies of the val92met, asp294his, or asp84glu alleles in the controls with skin types 3 and 4 were similar to those with skin types 1 and 2. Trend analysis, however, did identify an association (exact p = 0.048, two-sided test) between skin type and MC1R variants in the group comprising all controls with any one or more of these alleles. There was no association between MC1R alleles and hair color. Allele frequencies were not different in melanoma cases and controls. There were no associations between skin types and the proportion of cases with the asp294his or asp84glu alleles, though the association between skin type and the val92met allele approached significance (exact p = 0.09, two-sided test). Unexpectedly, in the group comprising all cases with one or more variant alleles, the proportion of subjects with variant alleles increased with skin types associated with tanning rather than burning, although trend analysis showed that this association did not quite reach statistical significance (exact p = 0.08, two-sided test). Asp84glu (but not val92met or asp294his) variant alleles were more common in subjects with blonde hair, although the relationship between the asp84glu allele and hair color did not achieve statistical significance (chi(2)3 = 6.16, exact p = 0.10). We interpret the data presented as indicating that polymorphism at MC1R does not appear a major determinant of skin type, at least in terms of these allelic variants. Furthermore, considered alone, these alleles are not susceptibility candidates for malignant melanoma.

Adult↗
PubMed1998

[Effect of gene polymorphism on detoxifying glutathione-S-transferase enzymes on chromosomal stability of squamous epithelial carcinomas in the area of the head-neck].

BACKGROUND: While cigarette smoking and chronic alcohol consumption are the major risk factors for the development of head and neck cancer, it is assumed that genetic factors contribute to risk. MATERIAL AND METHODS: We examined genotype frequencies from leukocyte DNA of 269 laryngeal cancer patients, 123 pharyngeal cancer patients and 216 controls. Polymorphisms at different glutathione-S-transferase (GST) gene loci were investigated. Losses of heterozygosity (LOH) at 12 different chromosomal gene loci were determined in 37 of the study patients by comparing blood and tumor cell DNA. The relationship between high risk genotypes and the occurrence of LOH was investigated. RESULTS: Glutathione-S-transferase high risk genotypes were identified at the first and third genes of the M family (GSTM1, GSTM3) and the first gene of the P family (GSTP1). These high risk genotypes are seen to have a statistically significant influence on the occurrence of LOH in the tumor tissue. CONCLUSION: There is evidence that the polymorphisms studied play a role in the carcinogenic process by influencing the chromosomal fragility which may lead to the inactivation of tumor suppressor genes or the activation of oncogenes.

Alcohol Drinking↗
PubMed1998

The glutathione S-transferase GSTP1 polymorphism: effects on susceptibility to oral/pharyngeal and laryngeal carcinomas.

We have examined the hypothesis that the polymorphic, glutathione S-transferase GSTP1 gene is a susceptibility candidate for squamous cell cancer of the oral/pharynx and larynx. We describe GSTP1 genotype frequencies in 380 cases and 180 controls. We found a lower frequency of GSTP1 AA in the oral/pharyngeal cases compared with controls (p = 0.003, odds ratio = 0.47) after correction for age and gender. We used an immunohistochemical approach to show widespread expression of the GSTP1 subunit throughout the pharynx and larynx. In uninfiltrated tissue, strong positivity was found throughout the squamous cell epithelium with the exception of the basal cell layer. The cilia of the respiratory epithelium of the larynx also showed positivity for GSTP1. In tumour tissue, expression of GSTP1 was similar in pharyngeal and laryngeal samples. These data are the first to show that polymorphism at GSTP1 mediates susceptibility to squamous cell cancer of the upper aerodigestive tract. No significant interactions were identified between GSTP1 and GSTM1, GSTM3, GSTT1 and the cytochrome P450 CYP1A1, CYP2D6 and CYP1A1 genotypes.

Alcohol Drinking↗