Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.2.7.5 (AOR)
 1,763 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Numerous epidemiological studies have established that occupational exposures and smoking are the two major known risk factors for the development of bladder cancer. Using data from the Missouri Cancer Registry, we investigated the hypothesis that individuals with occupationally-related bladder cancer are more likely to have a more invasive form of the disease. Data were analyzed for 2,893 white males diagnosed with primary bladder cancer in Missouri between 1984 and 1988. Of the 1,415 cases whose occupational status was recorded, 236 (17%) were employed in high-risk occupations. Cases with high-grade disease were more likely to have been employed in a high-risk occupation, after adjustment for age and smoking (adjusted odds ratio [AOR] = 1.7, 95% confidence interval [CI] = 1.1-2.6). High-risk workers under 60 years of age were most at risk for developing high-grade bladder tumors (AOR = 2.3, 95% CI = 1.0-5.3). There was no overall association between high-risk occupation and late-stage disease (AOR = 1.1, 95% CI = 0.7-1.5), but it was present in the men younger than 60 years of age (AOR = 2.0, 95% CI = 1.0-3.8). No association was found between tobacco use and grade (AOR = 1.1, 95% CI = 0.8-1.5), but cases with late-stage disease were more likely to be smokers (AOR = 1.5, 95% CI = 1.1-1.9). When occupations were examined individually, motor vehicle operators, truck drivers, vehicle mechanics, other mechanics, and janitors were among those most likely to be diagnosed with high-grade or late-stage tumors. Although further studies are necessary to confirm these results, they suggest that surveillance and targeted screening of workers in high-risk occupations may result in a greater yield of early invasive cancers and possibly decrease the mortality associated with this disease.
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PMID:Occupation, smoking, and the risk of high-grade invasive bladder cancer in Missouri. 160 16

Recent research suggested associations between pain and subsequent all-cause and cancer-specific mortality. This study examined death and cancer development within six years of reporting pain, among women in the Royal College of General Practitioners Oral Contraception Study. We found no associations between 'any' or 'chronic' pain and subsequent all-cause mortality or cancer. We found a higher risk of death from respiratory disease among women reporting pain (adjusted odds ratio [AOR] = 2.5), a higher mortality among women reporting chronic chest pain (AOR = 1.75), and a higher risk of subsequent cancer among women reporting head or abdomen pain. Given the high prevalence of pain symptoms, these findings may be important, and warrant further research.
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PMID:Pain and subsequent mortality and cancer among women in the Royal College of General Practitioners Oral Contraception Study. 1256 77

An imbalance in the activities of enzymes involved in the metabolism, conjugation and transport of xenobiotics may account for the variability in susceptibility to the development of complex diseases such as cancer between different population groups. In this study we investigated a functional polymorphism in the SULT1A1 gene in 245 patients and 288 controls. Previous studies have shown that the 638G-->A polymorphism that results in the substitution of arginine by histidine at codon 213 (SULT1A1*2) results in decreased SULT1A1 activity. The same group of samples used in this study had been previously genotyped for CYP3A5 genetic polymorphisms. Among Black subjects the burning of wood or charcoal for cooking and keeping warm was significantly associated with increased risk for oesophageal cancer (OC) (AOR, 15.2; P=0.001) as was the consumption of home-brewed beer (AOR, 6.97; P=0.0001). Among the Mixed Ancestry group, tobacco smoking combined with alcohol consumption were significantly associated with higher risk for OC (AOR, 5.18; P=0.0005). In both Blacks and Mixed Ancestry subjects, starting to smoke below the age of 20 years was associated with significantly increased risk for OC (AOR, 3.5 among the Blacks and AOR, 12 among the Mixed Ancestry). The homozygous SULT1A1*2/*2 genotype was associated with increased risk for OC among smokers. The SULT1A1*2/*2 genotype in combination with the CYP3A5 heterozygous genotypes was associated with significantly increased risk for OC (AOR, 3.60; P=0.001) with the risk being even higher among smokers compared with non-smokers. The above findings confirm the association between alcohol consumption and tobacco smoking with increased risk for OC. The genotype results show that SULT1A1*2/*2 genotype is associated with increased risk for OC among subjects exposed to tobacco-smoke-related carcinogens.
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PMID:Gene-environment interaction: the role of SULT1A1 and CYP3A5 polymorphisms as risk modifiers for squamous cell carcinoma of the oesophagus. 1627 71

NADPH-dependent alkenal/one oxidoreductase (Aor) was discovered to be highly inducible in rat liver following treatment with the cancer chemopreventive agent 3H-1, 2-dithiole-3-thione. Aor was further characterized as an Nrf2-regulated antioxidative enzyme that reduces carbon-carbon double bonds in a variety of alpha, beta-unsaturated aldehydes and ketones. 15-Deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) is a reactive membrane lipid metabolite that activates multiple pathways, including Nrf2-mediated induction of cytoprotective enzymes. Physiologically, it is postulated that 15d-PGJ2 alkylates key regulatory proteins via the electrophilic carbon centers found in two alpha, beta-unsaturated ketone moieties. This current study addresses the metabolism of 15d-PGJ2 by rat Aor (rAor) and subsequent deactivation of the Nrf2 signaling pathway by both rat and human AOR. We demonstrate that induction of NADPH-dependent quinone oxidoreductase activity by 15d-PGJ2 is markedly attenuated in mouse embryonic fibroblasts that overexpress rAor. Luciferase reporter assay and quantitative real-time PCR confirmed these findings. Concentrations required for doubling the NADPH-dependent quinone oxidoreductase response are increased from 1.8 microm in wild-type to >10 microm in rat Aor transgenic fibroblasts. 15d-PGJ2 is metabolized by recombinant rAor with a Km of 9.6 microm and k(cat) of 18.5 min(-1). The major product is 12,13-dihydro-15-deoxy-Delta12,14-prostaglandin J2 (dihydro-15d-PGJ2). The reduction of C=C by Aor yielding dihydro-15d-PGJ2 abolishes the inducibility in an antioxidant response element-driven luciferase assay. Collectively, these results demonstrate that 15d-PGJ2 can be catabolized by Aor, thereby attenuating subsequent Nrf2 signaling and possibly inflammatory and apoptotic processes also influenced by 15d-PGJ2.
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PMID:Nrf2-mediated induction of cytoprotective enzymes by 15-deoxy-Delta12,14-prostaglandin J2 is attenuated by alkenal/one oxidoreductase. 1685 69

DNA in most cells is regularly damaged by endogenous and exogenous mutagens. Unrepaired damage can result in apoptosis or may lead to unregulated cell growth and cancer. Inheritance of genetic variants at one or more loci results in reduced DNA repair capacity. This hospital-based case-control study examined whether polymorphisms in the DNA repair gene X-ray repair cross-complementing groups 1 (XRCC1) (Arg194Trp[C > T], Arg280His[G > A] and Arg399Gln[G > A]) play a role in susceptibility to skin cancer. We genotyped these polymorphisms for 212 histopathologically confirmed skin cancer cases (n = 114 basal cell carcinoma, n = 98 squamous cell carcinoma) and 207 age- and sex-matched healthy control cases in Korea. We found that individuals with the Arg/Gln and Arg/Gln + Gln/Gln genotypes at XRCC1 Arg399Gln(G > A) had an approximately 2-fold increased risk of basal cell carcinoma compared to individuals with the Arg/Arg genotype (adjusted odds ratio [AOR] = 2.812, 95% confidence interval [CI] 1.32-5.98, and AOR = 2.324, 95% CI 1.11-4.86). However, we observed that the 194Trp allele of the Arg194Trp(C > T) polymorphism was inversely associated with squamous cell carcinoma risk (Trp/Trp, AOR = 0.06, 95% CI 0.006-0.63). Our data suggest that the Arg194Trp and Arg399Gln polymorphisms may be differentially associated with skin cancer risk.
Cancer Sci 2007 May
PMID:Polymorphisms in the DNA repair gene XRCC1 associated with basal cell carcinoma and squamous cell carcinoma of the skin in a Korean population. 1735 63

Most cancer patients in westernised countries now want all information about their situation, good or bad, and many wish to be involved in decision-making. The attitudes to and use of shared decision-making (SDM) by cancer doctors is not well known. Australian cancer clinicians treating breast, colorectal, gynaecological, haematological, or urological cancer were surveyed to identify their usual approach to decision-making and their comfort with different decision-making styles when discussing treatment with patients. A response rate of 59% resulted in 624 complete surveys, which explored usual practice in discussing participation in decision-making, providing information, and perception of the role patients want to play. Univariate and multivariate analyses were performed to identify predictors of use of SDM. Most cancer doctors (62.4%) reported using SDM and being most comfortable with this approach. Differences were apparent between reported high comfort with SDM and less frequent usual practice. Multivariate analysis showed that specialisation in breast or urological cancers compared to other cancers (AOR 3.02), high caseload of new patients per month (AOR 2.81) and female gender (AOR 1.87) were each independently associated with increased likelihood of use of SDM. Barriers exist to the application of SDM by doctors according to clinical situation and clinician characteristics.
Br J Cancer 2007 Jul 02
PMID:The context influences doctors' support of shared decision-making in cancer care. 1755 91

Abnormalities of the tumor suppressor TP53 pathway are critical in the development of many cancers since it regulates cell cycle components and apoptosis. Murine double minute-2 (MDM2) protein is a central node in the p53 pathway and a direct negative regulator of p53. The MDM2 SNP309 (rs2279744) polymorphism increases MDM2 RNA and protein levels, attenuating the p53 pathway. The MDM2 SNP309 polymorphism was investigated in 1,787 Caucasian nonsmall cell lung cancer (NSCLC) patients and 1,360 healthy controls. Cases and controls were analyzed for associations with genotype and adjusted for age, gender, histology and smoking history. There were no overall associations between the MDM2 genotypes and risk of lung cancer (adjusted odds ratios [AORs] = 0.82 [95% confidence interval [CI] = 0.6-1.1] for the T/G genotype and AOR = 1.32 [95% CI = 0.9-2.0] for the G/G genotype). A statistically significant interaction (p = 0.01) was found between smoking and MDM2 genotypes. Consistent with this interaction, stratified analysis by pack-years of smoking demonstrated that the AORs of G/G vs. T/T were 1.56 (1.0-2.7), 1.46 (1.0-2.2), 0.80 (0.5-1.3) and 0.63 (0.4-1.1), respectively, for never, mild (<30 pack-years), moderate (30-57 pack-years) and heavy smokers (>or=58 pack-years). In conclusion, a strong gene-smoking interaction was observed between the MDM2 SNP309 and NSCLC risk.
Int J Cancer 2008 Feb 15
PMID:Genetic polymorphisms of MDM2, cumulative cigarette smoking and nonsmall cell lung cancer risk. 1795 85

The capacity for colonoscopy is limited and a method to prioritize patients for diagnostic colonoscopy is needed in health care centers. A retrospective cross-sectional cohort study was carried out in county and community endoscopy centers, which included 1,065 county and 279 community patients aged > or = 40 years undergoing diagnostic colonoscopy. We constructed a risk profile for proximal advanced neoplasms on diagnostic colonoscopy at the county center based on the size of the regression coefficients for independent risk factors from logistic regression. An advanced neoplasm was defined as one of size > or = 1 cm or containing villous histology, high-grade dysplasia, or cancer. In our county colonoscopy population (n = 929 after exclusions), the stepwise logistic regression analysis identified age > or = 60 years (adjusted odds ratio [AOR]: 2.60; 95% confidence interval [CI]:1.14, 6.14), iron deficiency anemia (AOR: 4.74; 95% CI: 2.07, 11.34), and an advanced neoplasm in the recto-sigmoid (AOR: 6.01; 95% CI: 2.02, 16.00) as the statistically significant predictors of an advanced proximal neoplasm. In the county population, the prevalence rates of an advanced proximal neoplasm and proximal high-grade dysplasia/cancer in the low-risk group were 0.71% (95% CI: 0.15, 2.05) and 0.24% (95% CI: 0.01, 1.31), respectively. Avoiding colonoscopy in this group would increase the capacity for colonoscopy by 46% in the higher risk groups. In a disparate community population (n = 237 after exclusions), this scoring system had a goodness-of-fit test showing high concordance (P = 0.51). This clinical profile stratified the risk for an advanced neoplasm proximal to the sigmoid in patients undergoing diagnostic colonoscopy. It identified a large subset of low-risk patients.
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PMID:A risk profile for advanced proximal neoplasms on diagnostic colonoscopy. 1853 6

Etiological risk factors for proximal (right-sided) colon cancers may be different to those of distal colon and rectal (left-sided) cancers if these tumors develop along distinct pathways. The CpG Island Methylator Phenotype (CIMP+) occurs in approximately 15% of colorectal cancers (CRC) and predominantly in the proximal colon. CIMP+ tumors have frequent methylation of gene promoter regions and increased tissue folate levels. The aim here was to determine whether polymorphisms in 2 genes involved in cellular methyl group metabolism were associated with different risks for right- and left-sided CRC. This population-based case-control study involved 859 incident cases of CRC and 973 sex and age-matched controls. Information on dietary folate and alcohol intake was obtained from food frequency questionnaires and information on the anatomical site of tumors from pathology reports. DNA was collected using FTA cards and genotyping performed for the MTHFR C677T and DeltaDNMT3B C-149T polymorphisms. The MTHFR 677 T allele was associated with increased risk for proximal colon cancer (adjusted odds ratio, AOR = 1.29) but decreased risk for distal cancers (AOR = 0.87). The increased risk for proximal cancers was especially pronounced in older individuals (AOR = 1.49) and those with a low folate diet (AOR = 1.67) or high alcohol consumption (AOR = 1.90). The DeltaDNMT3B-149 TT genotype was protective against proximal colon cancers (AOR = 0.65), but showed no association with the risk of distal colon and rectal cancers (AOR = 1.02). Epidemiological studies on dietary and genetic risk factors for CRC should take into account these may confer different risks for right- and left-sided tumors.
Int J Cancer 2009 Jul 01
PMID:The MTHFR C677T and DeltaDNMT3B C-149T polymorphisms confer different risks for right- and left-sided colorectal cancer. 1932 30

Condom promotion remains a key component of HIV prevention programs, complimenting recent successes in biomedical HIV prevention. Although condom use has increased in much of East Africa, it remains substantially below optimal levels. Negative rumors about condoms have been documented in East Africa, yet the prevalence and effects of belief in the negative rumors have not been explored. This study evaluated levels of belief in negative rumors about condoms, developed a Negative Condom Beliefs Scale, and assessed its accuracy in predicting willingness to use condoms. A cross-sectional, cluster survey (n = 370) was conducted representing adults in two rural districts in Northern Tanzania in 2008. Item agreement ranged from 35 to 53% for the following rumors regarding condoms: causing cancer, having holes, containing HIV, having worms, and the worms causing HIV. Items loaded on a single latent factor and had high internal consistency and convergent validity. In a multivariate model, negative condom score (AOR = 0.67, 95% CI = 0.6, 0.8) was the strongest single predictor of willingness to use condoms, followed by greater perceived anonymity in acquiring condoms (AOR = 4.36, 95% CI = 2.2, 8.6) and higher condom self-efficacy (AOR = 4.24, 95% CI = 2.0, 8.9). Our findings indicate high levels of subscription to negative beliefs about condoms, with two out of three respondents affirming belief in at least one negative condom rumor. This study highlights the relation between condom rumor beliefs and willingness to use condoms, and indicates avenues for future research and means for improving the design of HIV prevention programs.
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PMID:Condoms "contain worms" and "cause HIV" in Tanzania: Negative Condom Beliefs Scale development and implications for HIV prevention. 2287 34


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