Dataset Information

Association of a deletion of GSTT2B with an altered risk of oesophageal squamous cell carcinoma in a South African population: a case-control study.

ABSTRACT: Polymorphisms in the Glutathione S-transferase genes are associated with altered risks in many cancers, but their role in oesophageal cancer is unclear. Recently a 37-kb deletion polymorphism of GSTT2B that reduces expression of GSTT2 has been described. We evaluated the influence of the GSTT1 and GSTT2B deletion polymorphisms, and the GSTP1 Ile105Val polymorphism (rs1695) on susceptibility to oesophageal squamous cell carcinoma (OSCC) in the Black and Mixed Ancestry populations of South Africa.The GSTT1, GSTT2B and GSTP1 variants were genotyped in 562 OSCC cases and 907 controls, and tested for association with OSCC and for interaction with smoking and alcohol consumption. Linkage disequilibrium (LD) between the deletions at GSTT1 and GSTT2B was determined, and the haplotypes tested for association with OSCC. Neither the GSTT1 deletion nor the GSTP1 Ile105Val polymorphism was associated with OSCC risk in the Black or Mixed Ancestry populations. The GSTT2B deletion was not associated with OSCC risk in the Black population, but was associated with reduced risk of OSCC in the Mixed Ancestry population (OR=0.71; 95% CI 0.57-0.90, p=0.004). Case-only analysis showed no interaction between the GST polymorphisms and smoking or alcohol consumption. LD between the neighboring GSTT1 and GSTT2B deletions was low in both populations (r(2)(Black)=0.04; r(2)(MxA)=0.07), thus these deletions should be assessed independently for effects on disease risk.Although there was no association between the GSTT1 deletion polymorphism or the GSTP1 Ile105Val polymorphism with OSCC, our results suggest that the presence of the recently described GSTT2B deletion may have a protective effect on the risk of OSCC in the Mixed Ancestry South African population. This is the first report of the contribution of the GSTT2B deletion to cancer risk.

SUBMITTER: Matejcic M

PROVIDER: S-EPMC3246501 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Association of a deletion of GSTT2B with an altered risk of oesophageal squamous cell carcinoma in a South African population: a case-control study.

Matejcic Marco M Li DongPing D Prescott Natalie J NJ Lewis Cathryn M CM Mathew Christopher G CG Parker M Iqbal MI

PloS one 20111227 12

<h4>Background</h4>Polymorphisms in the Glutathione S-transferase genes are associated with altered risks in many cancers, but their role in oesophageal cancer is unclear. Recently a 37-kb deletion polymorphism of GSTT2B that reduces expression of GSTT2 has been described. We evaluated the influence of the GSTT1 and GSTT2B deletion polymorphisms, and the GSTP1 Ile105Val polymorphism (rs1695) on susceptibility to oesophageal squamous cell carcinoma (OSCC) in the Black and Mixed Ancestry populatio ...[more]

PMID: 22216261

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Project description:BACKGROUND:Tobacco smoking and red meat consumption are some of the known risk factors associated with the development of oesophageal cancer. N-acetytransferases (NAT1 and NAT2) play a key role in metabolism of carcinogenic arylamines present in tobacco smoke and overcooked red meat. We hypothesized that NAT1 and NAT2 genetic polymorphisms may influence the risk of oesophageal cancer upon exposure to environmental carcinogens. METHODS:Single nucleotide polymorphisms (SNPs) in the NAT1 and NAT2 genes were investigated by genotyping 732 cases and 768 healthy individuals from two South African populations to deduce the acetylator phenotype (slow, intermediate or rapid) from the combination of the genotyped SNPs. RESULTS:The 341 CC genotype (rs1801280) was significantly associated with a reduced risk for oesophageal cancer in the Mixed Ancestry population (OR?=?0.31; 95% CI 0.11-0.87). The NAT2 slow/intermediate acetylator status significantly increased the risk among cigarette smokers in the Black population (OR?=?2.76; 95% CI 1.69-4.52), as well as among alcohol drinkers in the Mixed Ancestry population (OR?=?2.77; 95% CI 1.38-5.58). Similarly, the NAT1 slow/intermediate acetylator status was a risk factor for tobacco smokers in the Black population (OR?=?3.41; 95% CI 1.95-5.96) and for alcohol drinkers in the Mixed Ancestry population (OR?=?3.41; 95% CI 1.70-6.81). In a case-only analysis, frequent red meat consumption was associated with a significantly increased cancer risk for NAT2 slow/intermediate acetylators in the Mixed Ancestry population (OR?=?3.55; 95% CI 1.29-9.82;?P?=?0.019), whereas daily white meat intake was associated with an increased risk among NAT1 slow/intermediate acetylators in the Black population (OR?=?1.82; 95% CI 1.09-3.04; P?=?0.023). CONCLUSIONS:Our findings indicate that N-acetylation polymorphisms may modify the association between environmental risk factors and oesophageal cancer risk and that N-acetyltransferases may play a key role in detoxification of carcinogens. Prevention strategies in lifestyle and dietary habits may reduce the incidence of oesophageal cancer in high-risk populations.

Project description:BACKGROUND:Computed tomography (CT) is commonly used in all stages of oesophageal squamous cell carcinoma (SCC) management. Compared to basic CT features, CT radiomic features can objectively obtain more information about intratumour heterogeneity. Although CT radiomics has been proved useful for predicting treatment response to chemoradiotherapy in oesophageal cancer, the best way to use CT radiomic biomarkers as predictive markers for determining resectability of oesophageal SCC remains to be developed. This study aimed to develop CT radiomic features related to resectability of oesophageal SCC with five predictive models and to determine the most predictive model. METHODS:Five hundred ninety-one patients with oesophageal SCC undergoing contrast-enhanced CT were enrolled in this study, and were composed by 270 resectable cases and 321 unresectable cases. Of the 270 resectable oesophageal SCCs, 91 cases were primary resectable tumours; and the remained 179 cases received neoadjuvant therapy after CT, shrank on therapy, and changed to resectable tumours. Four hundred thirteen oesophageal SCCs including 189 resectable cancers and 224 unresectable cancers were randomly allocated to the training cohort; and 178 oesophageal SCCs including 81 resectable tumours and 97 unresectable tumours were allocated to the validation group. Four hundred ninety-five radiomic features were extracted from CT data for identifying resectability of oesophageal SCC. Useful radiomic features were generated by dimension reduction using least absolute shrinkage and selection operator. The optimal radiomic features were chosen using multivariable logistic regression, random forest, support vector machine, X-Gradient boost and decision tree classifiers. Discriminating performance was assessed with area under receiver operating characteristic curve (AUC), accuracy and F-1score. RESULTS:Eight radiomic features were selected to create radiomic models related to resectability of oesophageal SCC (P-values <?0.01 for both cohorts). Multivariable logistic regression model showed the best performance (AUC?=?0.92 ± 0.04 and 0.87 ± 0.02, accuracy?=?0.87 and 0.86, and F-1score?=?0.93 and 0.86 in training and validation cohorts, respectively) in comparison with any other model (P-value <?0.001). Good calibration was observed for multivariable logistic regression model. CONCLUSION:CT radiomic models could help predict resectability of oesophageal SCC, and multivariable logistic regression model is the most predictive model.

Project description:Cutaneous squamous cell carcinoma (cSCC) has metastatic potential, but the prognostic value of current staging systems in nonselected patients is uncertain.To assess the effect of risk factors for metastasis and to evaluate validity and usefulness of 4 staging systems for cSCC using population-based data.This was a nationwide, population-based, nested case-control study. The Cancer Registry of Norway, which receives compulsory data on all cancers in the Norwegian population of approximately 5.2 million inhabitants. All patients diagnosed as having a primary invasive cSCC in the period 2000 to 2004 (n = 6721) were identified. Of these, 112 patients were diagnosed with metastasis within 5 years. As control patients, 112 patients with cSCC without metastases, matched for sex and age at diagnosis, were identified by random. Clinical data and biopsy specimens of primary cSCC were collected for all 224 patients. The biopsies were reexamined histologically by an experienced pathologist using well-established criteria for cSCC, yielding 103 patients with metastasis (cases) and 81 cSCC without metastasis (controls).The ability of 4 cSCC staging systems (ie, the American Joint Committee on Cancer, 7th edition [AJCC 7] staging system, the staging system used by Breuninger et al, the Brigham and Women's Hospital [BWH] staging system, and the AJCC, 8th edition [AJCC 8] staging systems) to identify patients who developed metastasis with 5 years of follow-up. External validation was performed by logistic regression, discrimination (sensitivity, specificity, proportion correctly classified, concordance index), and calibration (R2, Hosmer-Lemeshow test, plots) statistics.Of 6721 patients; 3674 (54.7%) were men and 3047 (45.3%) were women, with a mean age at diagnosis of 78 years. Of the 103 patients with cSCC diagnosed with metastasis within 5 years, 60 [58.3%] were men, and mean [SD] age 72.7 [13.5] years. Of the 81 patients with cSCC without metastasis, 51 [63.0%] were men, and mean [SD] age 74.6 [11.7] 15 years. The staging systems distinguished poorly to moderately between patients who developed metastasis and those who did not. The ability to cluster patients with similar outcomes within the same staging category was low, particularly when using the AJCC 7 system. Using the AJCC 7 system, the risk of metastasis for T2 patients was 3-fold, compared with T1 patients (OR, 2.96; 95% CI, 1.43-6.15). In the system used by Breuninger et al, high-risk categories for diameter and tumor thickness and the BWH system's T2b category collected relatively homogeneous groups. In the systems used by Breuninger et al and Brigham-Women's Hospital, risk of metastasis was significantly elevated with increasing stage or risk category. Using the system by Breuninger et al, the risk of metastasis was less than 3-fold for tumors in the high-risk category of the combined variable (OR, 2.72; 95% CI, 1.29-5.74). The BWH system gave ORs for metastasis at 4.6 (95% CI, 2.23-9.49) and 21.31 (95% CI, 6.07-74.88) for the T2a and T2b categories, respectively.Using population-based data, 4 current staging systems for cSCC were unsatisfactory in identifying nonselected cSCC patients at high risk for metastasis. The system used by Breuninger gave the best results.

Dataset Information

Association of a deletion of GSTT2B with an altered risk of oesophageal squamous cell carcinoma in a South African population: a case-control study.

Publications

Association of a deletion of GSTT2B with an altered risk of oesophageal squamous cell carcinoma in a South African population: a case-control study.

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