bluuebunny/crossref_metadata_2025_split huggingface dataset:
STK15 Polymorphisms and Association with Risk of Invasive Ovarian Cancer
Authors: DiCioccio Richard A. , Song Honglin , Waterfall Christy , Kimura Makoto T. , Nagase Hiroki , McGuire Valerie , Hogdall Estrid , Shah Mitul N. , Luben Robert N. , Easton Douglas F. , Jacobs Ian J. , Ponder Bruce A.J. , Whittemore Alice S. , Gayther Simon A. , Pharoah Paul D.P. , Kruger-Kjaer Susan 
Published: June 2022

Abstract
STK15 is a putative oncogene that codes for a centrosome-associated, serine/threonine kinase, the normal function of which is to ensure accurate segregation of chromosomes during mitosis. Amplification of STK15 has been reported in ovarian tumors, suggesting a role in ovarian cancer pathology. STK15 is polymorphic with two single nucleotide substitutions (449t/a and 527g/a) in evolutionarily conserved regions causing amino acid changes (F31I and V57I). Two other nucleotide substitutions (287c/g and 1891g/c) of unknown significance are in 5′ and 3′ untranslated regions (UTR), respectively. To learn more about the involvement of STK15 in ovarian cancer, we genotyped and haplotyped these polymorphisms in three population-based ovarian cancer case-control studies from the United Kingdom, United States, and Denmark with 1,821 combined cases and 2,467 combined controls and calculated risks for developing ovarian cancer. Genotypes of individual polymorphisms in control groups of the United Kingdom, United States, and Denmark conformed to Hardy-Weinberg equilibrium. In combined cases and combined controls, rare allele frequencies were 0.23 and 0.21 for I31, 0.16 and 0.17 for I57, 0.08 and 0.07 for 5′ UTR g, and 0.25 and 0.24 for 3′ UTR c, respectively. Using FF common homozygotes of F31I as comparator, there was increased ovarian cancer risk to FI heterozygotes (odds ratio, 1.18; 95% confidence interval, 1.01-1.36), II homozygotes (odds ratio, 1.25; 95% confidence interval, 0.89-1.75), and I31 allele carriers (odds ratio, 1.17; 95% confidence interval, 1.02-1.35) in the combined group data. For either V57I, 5′ UTR C/G, or 3′ UTR G/C, all genotypic ovarian cancer risks were essentially in unity relative to their respective common homozygotes, VV, cc, or gg. Haplotype analysis of combined group data revealed seven haplotypes with frequencies between 0.02 and 0.5, with c-F-V-g the most common. None of the haplotype-specific risks significantly differed from unity relative to c-F-V-g. These results suggest a model of dominant inheritance of ovarian cancer risk by the I31 allele of F31I and that the I31 allele may be a common ovarian cancer susceptibility allele of low penetrance.
A Comparison of Urinary Biomarkers of Tobacco and Carcinogen Exposure in Smokers
Authors: Murphy Sharon E. , Link Carrie A. , Jensen Joni , Le Chap , Puumala Susan S. , Hecht Stephen S. , Carmella Steven G. , Losey London , Hatsukami Dorothy K. 
Published: June 2022

Abstract
Recently, several potential harm reduction strategies, such as reduction in the number of cigarettes smoked and the use of modified cigarette products, have been discussed as possible means by which to reduce tobacco-related disease. To assess any potential reduction in harm by either of these approaches requires an accurate assessment of tobacco toxin exposure. We have recently completed a cigarette reduction study in which smokers were required to reduce the number of cigarettes smoked by 75%. This reduction took place over a 6-week period. We report here the comparison of urinary concentrations of tobacco alkaloid and tobacco carcinogen biomarkers in a subset of these same smokers during a 7-week period prior to any reduction in cigarette consumption. Urine samples were collected at four time points and analyzed for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and its glucuronide, 1-hydroxypyrene, anatabine, free nicotine, total nicotine (free plus glucuronidated), free cotinine, total cotinine (free plus glucuronidated), and total trans-3′-hydroxycotinine (free plus glucuronidated). Anatabine is a minor alkaloid that may be useful in assessing tobacco exposure in individuals using nicotine replacement therapies. Urinary anatabine levels were well correlated (P &lt; 0.0001) with both free and total nicotine (r = 0.753 and 0.773, respectively). Anatabine levels were also correlated with free cotinine (r = 0.465; P &lt; 0.001), total cotinine (r = 0.514; P &lt; 0.001), and total NNAL (r = 0.633; P &lt; 0.001). These data support the role of anatabine as a biomarker of tobacco exposure. 1-Hydroxypyrene is a biomarker of polycyclic aromatic hydrocarbon exposure, but unlike NNAL it is not tobacco specific. Whereas urinary concentrations of 1-hydroxypyrene were consistent across the four visits, the levels were not correlated with NNAL, anatabine, nicotine, or any nicotine metabolites.
Effects of Genetic Polymorphisms of Metabolic Enzymes on Cytokinesis-Block Micronucleus in Peripheral Blood Lymphocyte among Coke-Oven Workers
Authors: Leng Shuguang , Dai Yufei , Niu Yong , Pan Zufei , Li Xiaohua , Cheng Juan , He Fengsheng , Zheng Yuxin 
Published: June 2022

Abstract
Exploring the associations between genetic polymorphisms of metabolic enzymes and susceptibility to polycyclic aromatic hydrocarbon (PAH)–induced chromosomal damage is of great significance for understanding PAH carcinogenesis. Cytochrome P450, glutathione S-transferase, microsomal epoxide hydrolase, NAD(P)H:quinone oxidoreductase, and N-acetyltransferase are PAH-metabolizing enzymes. In this study, we genotyped for the polymorphisms of these genes and assessed their effects on cytokinesis-block micronucleus (CBMN) frequencies in peripheral blood lymphocytes among 141 coke-oven workers and 66 non–coke-oven worker controls. The geometric means of urinary 1-hydroxypyrene levels in coke-oven workers and the controls were 12.0 and 0.7 μmol/mol creatinine, respectively (P &lt; 0.01). The CBMN frequency (number of micronuclei per 1,000 binucleated lymphocytes) was significantly higher in coke-oven workers (9.5 ± 6.6‰) than in the controls (4.0 ± 3.6‰; P &lt; 0.01). Among the coke-oven workers, age was positively associated with CBMN frequency; the mEH His113 variant genotype exhibited significantly lower CBMN frequency (8.5 ± 6.5‰) than did the Tyr113/Tyr113 genotype (11.3 ± 6.4‰; P &lt; 0.01); the low mEH activity phenotype exhibited a lower CBMN frequency (8.6 ± 6.8‰) than did the high mEH activity phenotype (13.2 ± 6.7‰; P = 0.01); the GSTP1 Val105/Val105 genotype exhibited a higher CBMN frequency (15.0 ± 5.8‰) than did the GSTP1 Ile105/Ile105 or Ile105/Val105 genotypes (9.3 ± 6.5‰; P &lt; 0.01); the joint effect of high mEH activity phenotype and GSTM1 null genotype on CBMN frequencies was also found. Gene-environment interactions between occupational PAH exposure and polymorphisms of mEH and/or GSTM1 were also evident. These results indicate that the mEH, GSTP1, and GSTM1 polymorphisms may play a role in sensitivity or genetic susceptibility to the genotoxic effects of PAH exposure in the coke-oven workers.
Metabolic Syndrome and the Risk of Prostate Cancer in Finnish Men: A Population-Based Study
Authors: Laukkanen Jari A. , Laaksonen David E. , Niskanen Leo , Pukkala Eero , Hakkarainen Anna , Salonen Jukka T. 
Published: June 2022

Abstract
Objective: Individual components of metabolic syndrome have been linked to an increased risk for prostate cancers. We hypothesized that metabolic syndrome itself could confer an increased risk for incident prostate cancer. Methods: The participants were a population-based sample of 1,880 men from eastern Finland without history of cancer or diabetes mellitus at baseline. Results: The metabolic syndrome (WHO criteria) was present in 357 (19%) of subjects. During an average follow-up of 13 years, a total of 183 cancers occurred, of which 56 were due to prostate cancer. The metabolic syndrome at baseline was related to a 1.9-fold (95% confidence interval, 1.1-3.5) risk of prostate cancer after adjustment for age, alcohol consumption, physical fitness, and energy, fat, fiber, calcium, vitamin E, and α-linolenic acid intake. The association between metabolic syndrome and risk of prostate cancer was stronger among overweight and obese men with a body mass index ≥27 kg/m2 (adjusted relative risk, 3.0; 95% confidence interval, 1.2-7.3) than in lighter men (relative risk, 1.8; 95% confidence interval, 0.7-4.7). Conclusions: Middle-aged men with the metabolic syndrome were more likely to develop prostate cancer in this prospective population-based study. This finding suggests that efforts to curb the epidemic of overweight and sedentary lifestyle and the accompanying metabolic syndrome may decrease the risk for prostate cancer.
Robustness of Case-Control Studies of Genetic Factors to Population Stratification: Magnitude of Bias and Type I Error
Authors: Khlat Myriam , Cazes Marie-Hélène , Génin Emmanuelle , Guiguet Marguerite 
Published: June 2022

Abstract
Case-control studies of genetic factors are prone to a special form of confounding called population stratification, whenever the existence of one or more subpopulations may lead to a false association, be it positive or negative. We quantify both the bias (in terms of confounding risk ratio) and the probability of false association (type I error) in the most unfavorable situation in which only one high-risk subpopulation is hidden within the studied population, considering different scenarios of population structuring and varying sample sizes. In accord with previous work, we find that the bias is likely to be small in most cases. In addition, we show that the same applies to the associated type I error whenever the subpopulation is small in proportion. For instance, when the hidden subpopulation makes up 5% of the entire population, with an allelic frequency of 0.25 (versus 0.10) and a disease rate that is double, then the estimated bias is 1.07 and the type I error associated with a sample of 500 cases and 500 controls is 8% (instead of 5%). We also show that the type I error is substantially greater for a rare allele (frequency of 0.1) than for a common allele (frequency of 0.5) and analyze the pattern of increase of vulnerability to stratification bias with sample size. Based on our findings, we may therefore conclude that with moderate sample sizes the type I error associated with population stratification remains very limited in most realistic scenarios.
Prospective Study of Alcohol Drinking and Renal Cell Cancer Risk in a Cohort of Finnish Male Smokers
Authors: Mahabir Somdat , Leitzmann Michael F. , Virtanen Mikko J. , Virtamo Jarmo , Pietinen Pirjo , Albanes Demetrius , Taylor Philip R. 
Published: June 2022

Abstract
Of the few studies that have examined alcohol consumption in relation to risk of renal cell cancer (RCC), most are case-control studies. The extent to which alcohol affects RRC risk is unclear. We prospectively examined the association between total alcohol intake as well as specific types of alcoholic beverage and RCC in a large cohort of Finnish male smokers. Men from the Alpha-Tocopherol, BetaCarotene (ATBC) Cancer Prevention Study were followed for 12 years and RCC cases were identified. Alcohol consumption was assessed at baseline using a questionnaire previously shown to be both reproducible and valid. Cox proportional hazards modeling was used to adjust simultaneously for known or suspected risk factors for RCC. We ascertained 195 incident cases of RCC. In multivariate analysis, the relative risks and 95% confidence intervals (CI) of RCC according to increasing quartiles of total alcohol intake were 1.0, 0.91 (0.62-1.33), 0.94 (0.64-1.38), and 0.53 (0.34-0.83), respectively (P value for trend = 0.005); for spirit consumption, 1.0, 0.93 (0.63-1.Fspiait39), 0.84 (0.58-1.20), and 0.55 (0.36-0.85) (P for trend = 0.02); and for beer intake, 1.0, 1.22 (0.85-1.76), 0.83 (0.57-1.22), and 0.55 (0.36-0.85) (P for trend = 0.003). Too few people in this cohort drank wine to assess its association with risk of RCC. These data suggest that alcohol consumption is associated with decreased risk of RCC in male smokers. Because most of the risk reductions were seen at the highest quartile of alcohol intake and alcohol is a risk factor for a number of cancers particularly among smokers, these data should be interpreted with caution.
Peroxisome Proliferator-Activated Receptor-γ Suppresses Cyclooxygenase-2 Expression in Human Prostate Cells
Authors: Sabichi Anita L. , Subbarayan Vemparala , Llansa Norma , Lippman Scott M. , Menter David G. 
Published: June 2022

Abstract
Recent studies have found that cyclooxygenase-2 (COX-2) protein expression was low and inducible with cytokines in prostate cancer cells (in the absence of serum) and that, in contrast, COX-2 expression was high in normal prostate epithelial cells (EC). Peroxisome proliferator-activated receptor-γ (PPAR-γ) was expressed at high levels in the prostate cancer cell line PC-3 but not in ECs. In contrast to previous findings by others, PPAR-γ ligands did not induce PPAR-γ expression in EC or PC-3. The present study examined the relationship between PPAR-γ and COX-2 expression patterns in EC and PC-3 in the presence and absence of serum and/or the PPAR-γ agonist 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2). We also evaluated the effects that the forced expression of PPAR-γ1 and PPAR-γ2 had on COX-2 in ECs. We found that expression of PPAR-γ and COX-2 protein was inversely correlated in ECs and PC-3. Low COX-2 expression in PC-3 was up-regulated by serum, and 15d-PGJ2 blocked serum-induced COX-2 expression and activity in a dose-dependent manner. 15d-PGJ2 had no effect on COX-2 expression in ECs or PPAR-γ expression in either cell type. However, forced expression of PPAR-γ1 or PPAR-γ2 in ECs suppressed the high level of endogenous COX-2. This effect was not isoform specific and was augmented by 15d-PGJ2. The present study showed that PPAR-γ activation can be an important regulator of COX-2 in prostate cells and may be an important target for prostate cancer chemoprevention.
Benzene Exposure Assessed by Metabolite Excretion in Estonian Oil Shale Mineworkers: Influence of GlutathioneS-Transferase Polymorphisms
Authors: Sørensen Mette , Poole Jason , Autrup Herman , Muzyka Vladimir , Jensen Annie , Loft Steffen , Knudsen Lisbeth E. 
Published: June 2022

AbstractMeasurement of urinary excretion of the benzene metabolites S-phenylmercapturic acid (S-PMA) and trans,trans-muconic acid (t,t-MA) has been proposed for assessing benzene exposure, in workplaces with relatively high benzene concentrations. Excretion of S-PMA and t,t-MA in underground workers at an oil shale mine were compared with the excretion in workers engaged in various production assignments aboveground. In addition, possible modifying effects of genetic polymorphisms in glutathione S-transferases T1 (GSTT1), M1 (GSTM1), and P1 (GSTP1) on the excretion of S-PMA and t,t-MA were investigated. Fifty underground workers and 50 surface workers participated. Blood samples and three urine samples were collected from each worker: (a) a preshift sample collected the morning after a weekend, (b) a postshift sample 1 collected after the first shift, and (c) a postshift sample 2 collected after the last shift of the week. Personal benzene exposure was 114 ± 35 μg/m3 in surface workers (n = 15) and 190 ± 50 μg/m3 in underground workers (n = 15) in measurements made prior to the study. We found t,t-MA excretion to be significantly higher in underground workers after the end of shifts 1 and 2 compared with the corresponding surface workers. The same picture, although not significant, was seen for S-PMA excretion. Excretion of S-PMA and t,t-MA was found to increase significantly during the working week in underground workers but not in those employed on the surface. Both t,t-MA and S-PMA excretion were significantly higher in smokers compared with nonsmokers. Subjects carrying the GSTT1 wild-type excreted higher concentrations of S-PMA than subjects carrying the null genotype, suggesting that it is a key enzyme in the glutathione conjugation that leads to S-PMA. The results support the use of benzene metabolites as biomarkers for assessment of exposure at modest levels and warrant for further investigations of health risks of occupational benzene exposure in shale oil mines.
Lack of Effect of Celecoxib on Prostaglandin E2 Concentrations in Nipple Aspirate Fluid from Women at Increased Risk of Breast Cancer
Authors: Sauter Edward R. , Schlatter Lisa , Hewett John , Koivunen Debra , Flynn John T. 
Published: June 2022

Abstract
Background: Cyclooxygenase enzymes (COX-1, COX-2, and COX-3) convert arachidonic acid to prostaglandins, prostacyclins, thromboxanes, and other hydroxy fatty acids. Among these, prostaglandin E2 (PGE2) has tumor growth-promoting activity. The COX-2 isoform is the primary enzyme involved in PGE2 production in cancerous tissue.
Objective/Hypothesis: We administered the COX-2 inhibitor celecoxib (200 mg b.i.d.) to women at increased breast cancer risk. Our hypothesis was that PGE2 would be secreted in breast nipple aspirate fluid (NAF), that levels in NAF would be higher than in corresponding plasma, and that celecoxib would decrease PGE2 levels in NAF (reflecting a decreased breast tissue eicosanoid production) and plasma.
Specific Aim: To determine if PGE2 concentrations in NAF and plasma decrease after a 2-week course of celecoxib and then return to baseline 2 weeks after stopping the medication (washout).
Study Design: NAF and plasma were collected before celecoxib treatment, 2 weeks after taking celecoxib, and 2 weeks after washout. Each woman served as her own control.
Results: PGE2 concentrations in NAF and plasma were detectable in samples using two measurement techniques. On average, NAF PGE2 levels were 81-fold higher in NAF than in matched plasma. Technically, there were differences in PGE2 concentrations measured in similar fluids depending on the assay technique used (RIA versus chemiluminescence immunoassay). There were no significant decreases in PGE2 concentrations after celecoxib administration.
Conclusions: PGE2 can be measured in NAF. PGE2 levels are concentrated in NAF when compared with matched plasma samples. Celecoxib 200 mg b.i.d. does not appear to significantly decrease PGE2 concentrations in NAF and plasma.
Association of GSTM1, GSTT1, and GSTP1 Gene Polymorphisms with the Risk of Prostate Cancer: A Meta-analysis
Authors: Ntais Christos , Polycarpou Anastasia , Ioannidis John P.A. 
Published: June 2022

Abstract
The glutathione S-transferase (GST) gene superfamily encodes for enzymes involved in conjugation of electrophilic compounds to glutathione. Several polymorphisms in the GST genes have been implicated as risk factors for prostate cancer. We did a meta-analysis of 11 studies with GSTM1 genotyping (2,063 prostate cancer cases and 2,625 controls), 10 studies with GSTT1 genotyping (1,965 cases and 2,554 controls), and 12 studies with GSTP1 genotyping (2,528 cases and 3,076 controls). The random effects odds ratio was 1.08 [95% confidence interval (95% CI), 0.93-1.25, no significant between-study heterogeneity] for the GSTM1 null versus nondeleted genotype and 0.90 (95% CI, 0.73-1.12; P = 0.03 for heterogeneity) for the GSTT1 null versus nondeleted genotype. Overall, the random effects odds ratio was 1.05 (95% CI, 0.90-1.21; P &lt; 0.01 for heterogeneity) for the GSTP1-Val versus GSTP1-Ile allele. For all three polymorphisms, there was a trend for the presence of an association in the earliest published studies, but this did not seem to be validated in subsequent research. For GSTT1, larger studies gave different results than smaller ones. The meta-analysis shows that these three polymorphisms are unlikely to be major determinants of susceptibility to prostate cancer on a wide population basis.
Poly (AT) Polymorphism in Intron 11 of the XPC DNA Repair Gene Enhances the Risk of Lung Cancer
Authors: Marín M. Soledad , López-Cima M. Felicitas , García-Castro Laura , Pascual Teresa , Marrón Manuel G. , Tardón Adonina 
Published: June 2022

Abstract
Reduced DNA repair capacity due to inherited polymorphisms may increase the susceptibility to smoking-related cancers. In this report, we investigate the relationship between xeroderma pigmentosum complementary group C poly (AT) insertion/deletion polymorphism (XPC-PAT) of the XPC gene and lung cancer risk in a hospital-based case-control study of 359 newly diagnosed lung cancer patients and 375 control subjects matched on age, sex, and catchment area. The XPC genotype was determined by PCR-RFLP, and the results were analyzed using logistic regression, adjusting for relevant covariates. We found that the frequency of the PAT+/+ genotype was higher in the cases (20.6%) than in the controls (14.1%; P = 0.057) and that the PAT+/+ subjects were at significantly increased risk for lung cancer [adjusted odds ratio (OR), 1.60; 95% confidence interval (95% CI), 1.01-2.55]. Stratified analysis revealed that the risk was higher in former smokers (OR, 2.15; 95% CI, 1.07-4.31) and older people (OR, 2.76; 95% CI, 1.02-7.51), although this probably occurs due to 63.4% of cases older than 73 years being ex-smokers. When stratified by histologic type, the variant genotype was associated with statistically significant increased risk for squamous cell carcinoma (OR, 1.93; 95% CI, 1.06-3.51). In conclusion, our findings support the hypothesis that PAT and intron 11 C/A XPC polymorphisms are linked in the Spanish population and may contribute to the risk of developing lung cancer probably due to a higher frequency of deletion of exon 12 and reduced DNA repair capacity of the XPC protein.
BRCA1 and BRCA2 Mutations in a Study of African American Breast Cancer Patients
Authors: Pal Tuya , Permuth-Wey Jenny , Holtje Tricia , Sutphen Rebecca 
Published: June 2022

Abstract
The spectrum of mutations in BRCA1 and BRCA2 among African Americans has not been well characterized because most studies to date have been done in Caucasian families. According to Myriad Genetic Laboratories, Inc., only ∼3% of individuals undergoing BRCA1/BRCA2 testing reported African American ancestry. Data from previous studies show that among African American women a greater proportion of breast cancer cases are diagnosed at age &lt;45 years in comparison with Caucasians. Because breast cancer occurring at a young age is one of the hallmarks of high penetrance genes, the prevalence, spectrum, and effects of BRCA1/BRCA2 mutations may differ substantially between African Americans and Caucasians, and further investigation is warranted.
We conducted a hospital-based study of African American breast cancer patients with early age at diagnosis (≤45 years) or family history of breast or ovarian cancer. We identified four deleterious mutations in BRCA1 or BRCA2 among the 10 families tested, of which two were novel BRCA2 mutations, one was the west African founder mutation (BRCA1 943ins10), and one was a recurrent mutation that may be a candidate for a second African American founder mutation (BRCA1 IVS13+1G&gt;A). Our results support previous data in demonstrating that (a) the spectrum of mutations among African Americans is unique, (b) family history of breast cancer is an important predictor of hereditary cancer susceptibility among African Americans, and (c) empirical data may be useful in estimating mutation risk among African Americans.