Common genetic polymorphisms in the 5'-flanking region of the SULT1A1 gene: haplotypes and their association with platelet enzymatic activity.

SULT1A1 is a phase II detoxification enzyme involved in the biotransformation of a wide variety of endogenous and exogenous phenolic compounds. Human platelet SULT1A1 enzymatic activity shows marked inter-individual variability and a common coding polymorphism, SULT1A1*1/*2, has been described that accounts for a proportion of this variability. We examined the 5'-flanking region of the SULT1A1 gene to determine if genetic variability in this portion of the gene influenced enzymatic activity. Direct sequencing revealed five common genetic polymorphisms (-624G>C, -396G>A, -358A>C, -341C>G and -294T>C) that were present at different allele frequencies in Caucasian, African-American and Chinese groups. Platelet SULT1A1 enzymatic activity was significantly correlated with individual promoter region polymorphisms and the associations were different between African-Americans and Caucasians. Haplotypes were constructed and platelet enzymatic activity according to haplotype was examined. The haplotypes were also significantly correlated with activity; haplotypes GAACT and GGACT (accounting for 13% and 5% of inter-individual variability in platelet activity, respectively) were important in Caucasians while haplotypes GAACC, GAACT and GGACC (accounting for 8%, 5% and 4% of variability) were significantly associated with activity in African-Americans. The coding region polymorphism, SULT1A1*1/*2 was in linkage disequilibrium with the promoter region polymorphisms and showed no effect on activity when examined in the context of the 5'-flanking region polymorphisms. These studies indicate that variation in the promoter region of the SULT1A1 gene exerts a significant influence on enzymatic activity.

Human glutathione S-transferase A2 polymorphisms: variant expression, distribution in prostate cancer cases/controls and a novel form.

Variability of expression of the major glutathione S-transferases (GSTs) of liver, GSTA1 and GSTA2, is thought to affect the efficiency of detoxification of xenobiotics, including chemical carcinogens. Polymorphism of the GSTA1 regulatory sequence determines some of the variation of hepatic GSTA1 expression, but the polymorphisms in GSTA2 (exons 5 and 7) were not thought to affect GSTA2 activity. By examining GST protein expression for a set of human liver and pancreas samples (coupled with a cloning/polymerase chain reaction-restriction fragment length polymorphism strategy), we identified a novel substitution Pro110Ser (328C>T) and the corresponding novel variant GSTA2*E (Ser110Ser112Lys196Glu210), and confirmed the presence of variants GSTA2*A (Pro110Ser112Lys196Glu210), GSTA2*B (Pro110Ser112Lys196Ala210) and GSTA2*C (Pro110Thr112Lys196Glu210). GSTA2*C occurred at 30-60% (i.e. approximately 100-fold more frequent than previously reported) and GSTA2*E occurred (heterozygous) at approximately 11%. Hepatic expression of the Ser112 variants (GSTA2*A, GSTA2*B or GSTA2*E) was approximately four-fold higher than that of the Thr112 variant (GSTA2*C). Compared to any other variant, GSTA2E had lower rates of catalysis towards 1-chloro-2,4-dinitrobenzene (CDNB), 4-vinylpyridine, and cumene-, t-butyl- and arachidonic acid hydroperoxides, although kcat/Km for CDNB were similar for all four variants. Using a prostate cancer case-control population, it was found that GSTA1*A/GSTA2 C335 and GSTA1*B/GSTA2 G335 were in linkage disequilibrium in Caucasians but not in African-Americans. However, there were no significant differences in the distribution of these polymorphisms or resultant haplotypes by case status. Nevertheless, the rare genotypes, GSTA2*E/*E and GSTA1*B/*B + GSTA2*C/*C (potential low GSTA2 activity and low hepatic GSTA1 and GSTA2 expression, respectively) could increase the risk of adverse effects of xenobiotics via compromised efficiency of detoxification.

Association of SULT1A1 phenotype and genotype with prostate cancer risk in African-Americans and Caucasians.

Exposure to heterocyclic amines may increase prostate cancer risk. Human sulfotransferase 1A1 (SULT1A1) is involved in the bioactivation of some dietary procarcinogens, including the N-hydroxy metabolite of the food-borne heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo(4,5-b) pyridine. This study compares a polymorphism in the SULT1A1 gene, SULT1A1 enzyme activity, meat consumption, and the risk of prostate cancer in a population based case-control study. Prostate cancer patients (n = 464) and control individuals (n = 459), frequency matched on age and ethnicity, provided informed consent, answered a survey, and provided a blood sample. Platelets were isolated for phenotype analysis, and DNA was isolated from lymphocytes for genotype determination. Meat consumption was assessed using a dietary questionnaire. Caucasians homozygous for the SULT1A1*1 high activity allele were at increased risk for prostate cancer [odds ratio (OR), 1.68; 95% confidence interval (CI), 1.05-2.68] compared with individuals homozygous for the low-activity allele. The association between SULT1A1 genotype and prostate cancer risk in African-Americans did not reach significance (OR, 1.60; 95% CI, 0.46-5.62). When SULT1A1 activity was considered, there was a strong association between increased SULT1A1 activity and prostate cancer risk in Caucasians (OR, 3.04; 95% CI, 1.8-5.1 and OR, 4.96; 95% CI, 3.0-8.3, for the second and third tertiles of SULT1A1 activity, respectively) compared with individuals in the low enzyme activity tertile. A similar association was also found in African-American patients, with ORs of 6.7 and 9.6 for the second and third tertiles of SULT1A1 activity (95% CI, 2.1-21.3 and 2.9-31.3, respectively). When consumption of well-done meat was considered, there was increased risk of prostate cancer (OR, 1.42; 95% CI, 1.01-1.99 and OR, 1.68; 95% CI, 1.20-2.36 for the second and third tertiles, respectively). When SULT1A1 activity was stratified by tertiles of meat consumption, there was greater risk of prostate cancer in the highest tertile of meat consumption. These results indicate that variations in SULT1A1 activity contributes to prostate cancer risk and the magnitude of the association may differ by ethnicity and be modified by meat consumption.

Esophageal and gastric cardia cancer risk and folate- and vitamin B(12)-related polymorphisms in Linxian, China.

Linxian, a rural county in North Central China, has among the highest rates of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in the world. Its inhabitants have documented chronic nutritional inadequacies, including folate and vitamin B(12) deficiencies. Using a cohort we have been studying in Linxian since 1985, we examined the relationship between incident ESCC and GCA cancers and three polymorphisms in two genes that code for enzymes that require folate and B(12) as cofactors: methionine synthase reductase (MTRR) A66G and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C. We conducted a case-cohort study among 4005 individuals in our cohort who were alive and cancer free in 1991 and had blood samples adequate for DNA extraction. Polymorphisms were measured on all 219 incident cancers (129 ESCCs and 90 GCAs) that developed through May 1996 and on 398 controls. Cox proportional hazard models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Individuals with the MTHFR 677TT genotype had significantly higher combined ESCC/GCA risks (RR, 1.45; 95% CI, 1.02-2.05) than those with CC or CT genotypes. The only subjects to have MTHFR 1298CC were three ESCC cases (P = 0.03). Compared with subjects with the MTRR 66AA genotype, subjects with the AG or GG genotypes had significantly higher risk of ESCC (RR, 1.59; 95% CI, 1.04-2.42). No association was observed for GCA. Our results suggest that the MTHFR C677T and MTRR A66G polymorphisms influence the risk of ESCC and GCA in this population.

Identification of aminobiphenyl derivatives in commercial hair dyes.

A recent epidemiological study suggested that aromatic amines present in hair dyes may contribute to an increased risk of bladder cancer (Gago-Dominguez, et al. (2003) Carcinogenesis 24, 483-489). Moreover, a preliminary study linked frequent hair dye usage with elevated levels of DNA adducts of 4-aminobiphenyl (4-ABP) in human epithelial breast cells (Gorlewska, et al. Proc. Am. Assoc. Cancer Res. 43, 1018-1019). Therefore, we sought to determine if 4-ABP, a recognized human urinary bladder carcinogen, is present in commercial hair dyes. 4-ABP was isolated from dyes by solvent extraction with hexane, followed by silica gel chromatography, either with or without chemical treatment of the extract with Zinc/HCl, and a final purification with a mixed cation exchange reversed-phase resin. The identity of 4-ABP was confirmed by both HPLC with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and gas chromatography with negative ion chemical ionization mass spectrometry (GC-NICI-MS) following chemical derivatization with pentafluoropropionic anhydride (PFPA). The levels of 4-ABP ranged from not detectable (<0.29 parts per billion (ppb)) up to 12.8 ppb. The noncarcinogenic isomer 2-aminobiphenyl (2-ABP) was also found at quantities up to 310 ppb. 4-ABP was detected in eight of the 11 hair dyes and found in black, red, and blonde hair dyes but not in brown hair dyes. 1,4-Phenylenediamine (PPD) is a key constituent for color development of many permanent hair dyes. Some batches of chemical research grade PPD were contaminated with 4-ABP (up to 500 ppb) and 2-ABP (up to 70 parts per million) and may be a source of ABP contamination in hair dyes. These analytical data demonstrate that 4-ABP is present in some hair dyes. Studies on dermal absorption and bioavailability of 4-ABP from hair dyes are required to determine if this aromatic amine contributes to the increased risk of bladder cancer reported in frequent users of hair dyes.

Gene-environment interactions between the codon 194 polymorphism of XRCC1 and antioxidants influence lung cancer risk.

X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene whose polymorphisms appear to influence the risk of lung cancer. We explored the influence of antioxidants on the association between the codon 194 arganine to tryptophan substitution polymorphism of XRCC1 and lung cancer risk. In a case-control study nested within a cohort of tin miners the cases were those diagnosed with lung cancer over 6 years of follow-up (n = 108). Two controls, matched on age and sex, were selected for each case by incidence density sampling. Individuals with the variant Arg194Trp allele seemed to be at lower risk for lung cancer (odds ratio (OR): 0.7, 95% confidence interval (95%CL): 0.4-1.2). Furthermore, high serum alpha-tocopherol (OR: 0.4, 95%CL: 0.2-0.9) and retinol (OR: 0.4, 95%CL: 0.2-0.9) levels were associated with significantly reduced risk of lung cancer among individuals with the Arg194Trp variant allele, but not among individuals with the wild-type genotype. In addition, the Arg194Trp variant reduced the risk of lung cancer associated with increased serum carotenoids compared to those with the homozygous wild-type allele. Our results show that Arg194Trp XRCC1 variant modifies the association between serum antioxidants and lung cancer risk.

Analysis of total meat intake and exposure to individual heterocyclic amines in a case-control study of colorectal cancer: contribution of metabolic variation to risk.

A case-control study of colorectal cancer, consisting of 157 cases and 380 controls matched by sex, ethnicity, decade of age and county of residence was performed to explore the associations between environmental exposure, metabolic polymorphisms and cancer risk. Participants were required to provide a blood sample, undergo caffeine phenotyping and complete an in-person interview that evaluated meat consumption, cooking methods and degree of doneness. A color atlas of foods cooked to different degrees of doneness was used to estimate food preparation techniques and food models were used to estimate serving portion sizes. Data was analyzed using a reference database of heterocyclic amine (HCA) exposure based on the food preferences chosen from the atlas. Data regarding individual food items cooked to different levels of doneness, as well as summary variables of foods and of food groups cooked to different degrees of doneness were also evaluated in a univariate analysis for association with colorectal cancer case status. Three measures of metabolic variation, hGSTA1 genotype, SULT1A1 genotype and the phenotype for CYP2A6 were also evaluated for possible association with colon cancer. While higher exposure to HCAs was strongly associated with colorectal cancer risk, increased consumption of five red meats cooked well done or very well done produced comparable odds ratios (OR) for colorectal cancer risk (OR=4.36, 95% CI 2.08-9.60) for the highest quartile of exposure. Similarly, individuals in the most rapid CYP2A6 phenotype quartile showed an odds ratio (OR = 4.18, 95% CI 2.03-8.90). The ORs for the low activity hGSTA1 and low activity SULT1A1 alleles were 2.0, 95% CI 1.0-3.7 and 0.6, 95% CI 0.3-1.1, respectively. Individual measures of specific HCAs provided little improvement in risk assessment over the measure of meat consumption, suggesting that exposure to other environmental or dietary carcinogens such as nitrosamines or undefined HCAs may contribute to colorectal cancer risk.

Limitations of the case-only design for identifying gene-environment interactions.

The case-only design, which requires only diseased subjects, allows for estimation of multiplicative interactions between factors known to be independent in the study population. The design is being used as an alternative to the case-control design to study gene-environment interactions. Estimates of gene-environment interactions have been shown to be very efficient relative to estimates obtained with a case-control study under the assumption of independence between the genetic and environmental factors. In this paper, the authors explore the robustness of this procedure to uncertainty about the independence assumption. By using simulations, they demonstrate that inferences about the multiplicative interaction with the case-only design can be highly distorted when there is departure from the independence assumption. They illustrate their results with a recent study of gene-environment interactions and risk of lung cancer incidence in a cohort of miners from the Yunnan Tin Corporation in southern China. Investigators should be aware that the increased efficiency of the case-only design is a consequence of a strong assumption and that this design can perform poorly if the assumption is violated.

Cyclooxygenase-2, P-glycoprotein-170 and drug resistance; is chemoprevention against multidrug resistance possible?

BACKGROUND: It is generally accepted that P-glycoprotein 170 (MDR1/Pgp170) expression in breast tumors results in poor response to chemotherapy due to its ability to export chemotherapeutic agents. Studies indicate that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may enhance the anti-tumor activity of cancer chemotherapeutic agents and reduce the risk of many cancers. The best known function of NSAIDs is to block the enzyme cyclooxygenase (Cox), the rate limiting enzyme in the conversion of arachidonic acid to prostaglandins. In this study we investigated whether expression of the inducible isoform of Cox (Cox-2) is linked with the multidrug resistance phenotype in breast cancer. METHODS: Expression of Cox-2 and MDR1/Pgp170 was investigated in tumor specimens along with normal epithelium in breast cancer patients using immunohistochemisrty. Expression of Cox-2, MDR1/Pgp170, Protein Kinase C (PKC), and Activator Protein 1 (AP1) were investigated in a series of increasingly resistant human MCF-7 breast cancer cells compared to wild type using immunohistochemistry, Western blots, Northern blots, RT-PCR, and Southern blots. RESULTS: Immunohistochemical analyses of human breast tumor specimens revealed a strong correlation between expression of Cox-2 and MDR1/Pgp170. In drug resistant cell lines that over-express MDR1/Pgp170 there was also significant up-regulation of Cox-2 expression. In addition, PKC and AP1 subunits c-Jun and c-Fos were also upregulated. We hypothesized that increased prostaglandin production by Cox-2 induces PKC and the expression of transcriptional factor c-Jun, which in turn, induces the expression of MDR1/Pgp170. CONCLUSION: We propose that pretreatment with selective Cox-2 inhibitors may be useful in the prevention of multidrug resistance in response to cancer chemotherapy and should be further evaluated.

Influence of antioxidants and the CYP1A1 isoleucine to valine polymorphism on the smoking--lung cancer association.

To evaluate the association between CYP1A1 genotype and lung cancer risk and to assess the effect of CYP1A1 genotype and antioxidant supplementation on the smoking--lung cancer relationship we conducted a case-control study nested within a large cancer prevention trial cohort. Controls (n = 324) were matched to cases (n = 282) on age (+/- 5 years), intervention group and study clinic in a 1:1 ratio, using incidence density sampling. Genotype was determined by a PCR-based method and logistic regression was used to calculate relative risk estimates. Overall, we found no association between CYP1A1 genotype and lung cancer risk. CYP1A1 genotype did not modify the effect of smoking on lung cancer risk. However, in an examination of subgroups defined by randomized intervention assignment our findings suggest that alpha-tocopherol supplementation may reduce the risk of lung cancer associated with cumulative smoking exposure regardless of CYP1A1 genotype with the greatest effect seen among those with the variant CYP1A1 allele.

Variation in the promoter region of the myeloperoxidase gene is not directly related to lung cancer risk among male smokers in Finland.

In order to examine whether a polymorphism in the promoter region of the myeloperoxidase (MPO) gene is associated with lung cancer among male smokers, we conducted a case-control study nested within a Finnish clinical trial cohort. Although we found no evidence of an overall association between lung cancer risk and MPO genotype, the variant MPO genotype was associated with an increased risk of lung cancer among a subset of older men. These findings contrast with those from previous studies that report decreased lung cancer risk among MPO variant individuals.

Polymorphisms of the DNA repair gene XRCC1 and lung cancer risk.

We explored the association between polymorphisms of the DNA repair gene XRCC1 (codons 194, 280, and 399) and lung cancer risk in a case-control study nested within a cohort of tin miners. Cases were those diagnosed with lung cancer over 6 years of follow-up (n = 108). Two controls, matched on age and sex, were selected for each case by incidence density sampling. Of the three polymorphisms, only the XRCC1 Arg280His allele was associated with increased lung cancer risk (odds ratio, 1.8; 95% confidence interval, 1.0-3.4) after adjustment for radon and tobacco exposure. In addition, individuals with the variant Arg280His allele who were alcohol drinkers seemed to be at higher risk for lung cancer compared with those with the homozygous wild-type genotype. Conversely, individuals with the variant Arg194Trp allele who were alcohol drinkers seemed to be at lower risk for lung cancer compared with those with the homozygous wild-type genotype. Polymorphisms of XRCC1 appear to influence risk of lung cancer and may modify risk attributable to environmental exposures.

Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk.

Human cellular glutathione peroxidase 1 (hGPX1) is a selenium-dependent enzyme that participates in the detoxification of hydrogen peroxide and a wide range of organic peroxides. We conducted a case-control study nested within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study cohort to evaluate the association between the proline to leucine polymorphism at codon 198 of hGPX1 and lung cancer risk. Cases (n = 315) were matched to controls on age (+/-5 years), intervention group, and study clinic using incidence density sampling in a 1:1 ratio. The prevalence of the hGPX1 Pro198Leu variant allele was 58% for controls and 71% for cases (P < 0.001). Using conditional logistic regression, we found a significant association between hGPX1 genotype and lung cancer risk. The odds ratio for heterozygotes was 1.8 (95% confidence interval, 1.2-2.8) and 2.3 (95% confidence interval, 1.3-3.8) for homozygous variants compared to wild-type individuals. Due to its high prevalence, the hGPX1 variant may contribute significantly to lung cancer risk among Caucasians but not among ethnic Chinese who do not exhibit this polymorphism.

Serum carotenoids are associated with increased lung cancer risk among alcohol drinkers, but not among non-drinkers in a cohort of tin miners.

To examine the association between pre-diagnostic serum carotenoid levels and lung cancer risk and the effects of alcohol intake on the carotenoid-lung cancer relationship, we conducted a case-control study in an occupational cohort from the Yunnan Tin Corporation in China. During 6 years of follow-up, 339 cases of confirmed lung cancer were diagnosed. Among these cases, those who donated pre-diagnostic blood (n = 108) were eligible for this study. For each case, two individuals alive and free of cancer at the time of case diagnosis, matched on age, sex, and date of blood collection, were selected as controls. Serum beta-carotene (odds ratios (ORs) for tertiles: 1, 1.3, 2.0) and beta-cryptoxanthin (ORs for tertiles: 1, 1.8, 2.9) levels were positively associated with lung cancer risk after adjustment for tobacco use and radon exposure. Among alcohol drinkers, higher serum carotenoid levels were significantly associated with increased lung cancer risk (alpha-carotene OR 2.2, 95% confidence interval (CI) 1.1-4.4, beta-carotene OR 7.6, 95% CI 3.1-18.6, lutein/zeaxanthin OR 2.3, 95% CI 1.2-6.6 and beta-cryptoxanthin OR 7.6, 95% CI 2.7-21.5). Conversely, risk estimates among non-drinkers suggest a possible protective association for higher carotenoid levels.

Association between GSTM1*0 and squamous dysplasia of the esophagus in the high risk region of Linxian, China.

Individuals with specific phase I and phase II enzyme polymorphisms may be at increased risk for squamous cell carcinoma of the esophagus. However, to our knowledge there has been only one previous report that evaluates a potential role for these polymorphisms in increasing risk for preneoplastic squamous lesions of the esophagus. To explore this further, we examined polymorphisms in CYP1A1, CYP2E1, GSTM1 and GSTT1, both independently and in combination, for potential associations with the risk of biopsy-proven squamous dysplasia of the esophagus in asymptomatic adults from Linxian, a high risk region in China. Cases consisted of 56 individuals from an esophageal cancer screening study with an endoscopic biopsy diagnosis of mild or moderate squamous dysplasia. Each case was matched on age (+/- 1 year) and gender to a control. Controls were defined as screening study participants with an endoscopic biopsy diagnosis of normal mucosa or esophagitis. DNA was extracted from frozen cell samples obtained by cytologic balloon examination and genotyped using standard methods. Individuals who were GSTM1 null (homozygous for GSTM1*0) were found to have a tendency for an increased risk of esophageal squamous dysplasia (odds ratio=2.6, 95% CI, 0.9-7.4). No excess risks were observed for inheritance of other putative at risk genotypes CYP1A1*2B, CYP2E1*6 or GSTT1*0. The risk associated with the inheritance of combined genotypes was not significantly different than the risk estimates from the univariate analysis. These results are consistent with the notion that exposure to environmental carcinogens that are detoxified by GSTM1, such as polycyclic aromatic hydrocarbons, may contribute to the etiology of esophageal cancer in Linxian.

Serum tocopherols, selenium and lung cancer risk among tin miners in China.

OBJECTIVE: To evaluate the association of prediagnostic serum antioxidants and lung cancer risk we conducted a case-control study nested in an occupational cohort of tin miners. METHODS: Male workers free of cancer enrolled in the cohort. During up to 6 years of follow-up, 339 lung cancer cases were diagnosed and, among these cases, those who donated blood prospectively (n = 108) were eligible for this study. For each case, two controls alive and free of cancer at the time of case diagnosis were matched on age and date of blood collection. RESULTS: Overall, we observed no association between serum alpha-tocopherol, gamma-tocopherol or selenium levels and lung cancer risk. However, a significant gradient of decreasing lung cancer risk with increasing serum alpha-tocopherol was apparent for men less than 60 years old (odds ratio by tertile: 1.0, 0.9, 0.2; trend p = 0.002). Alpha-tocopherol was also protective in men who reported no alcohol drinking (OR by tertile: 1.0, 0.6, 0.3; trend p = 0.008). CONCLUSION: Although there were no significant overall associations between prospectively collected serum alpha-tocopherol, gamma-tocopherol or selenium and incidence of lung cancer, results from this study suggest that higher alpha-tocopherol levels may be protective in men less than 60 years old and in those who do not drink alcohol.

Prevalence of disease-related DNA polymorphisms among participants in a large cancer prevention trial.

Genetic susceptibility polymorphisms may be of substantial importance in the modulation of cancer risk. The prevalence for an array of polymorphic genes was determined in a cohort of male smokers who participated in a cancer prevention trial in Finland. A random sample of 120 individuals was selected from the trial cohort and the prevalence of variant alleles for nine genes was determined using a polymerase chain reaction-based approach. The prevalence values from this study were also compared with those of other populations derived from previous studies. Our results show that, with the exception of cytochrome P450-1A1 (CYP1A1) and cytochrome P450-2E1 (CYP2E1), all genes tested were sufficiently polymorphic to warrant an investigation of gene-environment studies. Most of the variant alleles, including alcohol dehydrogenase 3 (ADH3), glutathione-S-transferase (GSTM1), methionine synthase (MS), methylene tetrahydofolater reductase (MHTFR), CYP2E1 and CYP1A1, exhibited similar frequencies to other Caucasian populations. Interestingly, the prevalence of androgen receptor-CAG repeat (AR-CAG) and vitamin D receptor (VDR) polymorphisms differed significantly between the alpha-tocopherol, beta-carotene (ATBC) Study and other Caucasian populations. We present herein results from this survey and conclude that the ATBC study population in Finland is sufficiently heterogeneous to facilitate analysis of genetic polymorphisms and disease associations.

Expression of cyclooxygenase-2 in human adenocarcinomas of the gastric cardia and corpus.

Several studies indicate that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of gastric corpus and possibly gastric cardia cancers. The best known action of NSAIDs is to block the enzyme cyclooxygenase, the rate limiting enzyme in the conversion of arachidonic acid to prostaglandins. We investigated the expression of cyclooxygenase-2 (Cox-2) in adenocarcinomas of the gastric cardia (N=19) and corpus (N=15) and in adjacent normal epithelium from a high risk Chinese population. Immunohistochemical detection of Cox-2 revealed positive staining in 36% of the gastric cardia cancer cases and 60% of the gastric corpus cancer cases, whereas histologically normal tissue from the same patients were negative. Smooth muscle, stroma and inflammatory cells were also positive. Our results suggest that Cox-2 is overexpressed in a large proportion of adenocarcinomas of the gastric corpus and in a smaller number of gastric cardia cancer cases.

Expression of cyclooxygenase-2 in human squamous cell carcinoma of the esophagus; an immunohistochemical survey.

Several studies indicate that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of esophageal cancer. The best known function of NSAIDs action is to block the enzyme cyclooxygenase, the rate limiting enzyme in the conversion of arachidonic acid to prostaglandins. In this study we investigated the expression of cyclooxygenase-2 (Cox-2) in squamous cell cancers of the esophagus and in normal esophageal squamous epithelium. Immunohistochemical detection of Cox-2 revealed strong positive staining in the well-differentiated regions of esophageal tumors, whereas histologically normal squamous epithelium stained only weakly positive. Smooth muscle cells, some stromal and inflammatory cells were also positive. Poorly differentiated areas of the esophageal tumors were negative. Our results suggest that Cox-2 is over-expressed in well-differentiated regions of squamous cell cancers of the esophagus.

Cancer knowledge and misconceptions among immigrant Salvadorean men in the Washington, D.C. area.

Although Salvadoreans are the fourth largest group of Hispanics in the United States, little is known about their cancer knowledge, attitudes, and practices. There are no publications assessing cancer knowledge among Salvadorean men. In this cross-sectional survey, information was gathered from 706 immigrant Salvadorean men in Washington, D.C. The majority of these men knew that smoking causes cancer and that some cancers can be cured if detected early. However, the men in this survey had inadequate knowledge about symptoms of cancer and early detection methods. The most important predictor of cancer screening among older participants was enrollment in health insurance plans. Our study suggests that Salvadorean men would participate in cancer screening efforts if they had access to medical care. Educational programs to increase awareness of cancer and availability of preventive services may help prevent cancer in this population.