bluuebunny/crossref_metadata_2025_split huggingface dataset:
The T393C Polymorphism of the Gαs Gene (GNAS1) Is a Novel Prognostic Marker in Bladder Cancer
Authors: Frey Ulrich H. , Eisenhardt Andreas , Lümmen Gerd , Rübben Herbert , Jöckel Karl-Heinz , Schmid Kurt W. , Siffert Winfried 
Published: September 2005

Abstract
The G protein Gαs pathway is linked to proapoptotic signaling in cancer cell lines. To assess the role of the GNAS1 locus encoding Gαs as a genetic factor for disease progression of transitional cell carcinoma (TCC) of the bladder, we genotyped the synonymous T393C polymorphism in 254 patients with TCC (minor allele frequency: 0.43) to examine a potential association between genotypes and disease progression. Using Kaplan-Meier estimates to calculate 5-year probabilities of follow-up, we could show that progression-free survival, metastasis-free survival, and cancer-specific survival was significantly increased in TT genotypes (56%, 84%, 82%) compared with CC genotypes (35%, 53%, 58%). In multivariate Cox proportional hazard analysis, the T393C polymorphism was an independent prognostic factor for clinical outcome. Homozygous CC patients were at highest risk for progression [odds ratio (OR), 1.94; P = 0.020], metastasis (OR, 3.49; P = 0.005), and tumor-related death (OR, 2.49; P = 0.031) compared with TT genotypes. Heterozygous patients had an intermediate risk compatible with a gene-dose effect. Real-time PCR analysis of urothelial tumor tissue as well as adipose and heart tissue revealed that Gαs mRNA expression was highest in TT genotypes, indicating a proapoptotic effect in these genotypes. In conclusion, the GNAS1 T393C status associated with differential Gαs mRNA expression is a novel independent prognostic marker for clinical outcome supporting a functional role of Gαs in bladder cancer progression.
Plasma 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D and Risk of Breast Cancer
Authors: Bertone-Johnson Elizabeth R. , Chen Wendy Y. , Holick Michael F. , Hollis Bruce W. , Colditz Graham A. , Willett Walter C. , Hankinson Susan E. 
Published: September 2005

Abstract
Several lines of evidence suggest that vitamin D may reduce incidence of breast cancer, but few epidemiologic studies have addressed the relation of plasma vitamin D metabolites to the risk of this disease. We prospectively examined the relationship between plasma levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and risk of breast cancer in a case-control study nested within the Nurses' Health Study cohort. Blood samples were collected from study participants in 1989-1990. Breast cancer cases developing between blood collection and June 1, 1996, were matched to cancer-free controls on the basis of age, menopausal status, and other factors. Stored plasma samples from 701 cases and 724 controls were available for metabolite analysis. Cases had a lower mean 25(OH)D level than controls (P = 0.01), but mean 1,25(OH)2D levels were similar (P = 0.49). High levels of both metabolites were associated with a nonsignificant lower risk of breast cancer. Women in the highest quintile of 25(OH)D had a relative risk of 0.73 (95% confidence interval = 0.49-1.07; Ptrend = 0.06) compared with those in the lowest quintile. For 1,25(OH)2D, the comparable relative risk was 0.76 (95% confidence interval = 0.52-1.11; Ptrend = 0.39). For both metabolites, the association was stronger in women ages 60 years and older, but results were not statistically significant. Our findings suggest that high levels of 25(OH)D, and perhaps 1,25(OH)2D, may be modestly associated with reduced risk of breast cancer.
Gene-Specific Methylation and Subsequent Risk of Colorectal Adenomas among Participants of the Polyp Prevention Trial
Authors: Woodson Karen , Weisenberger Daniel J. , Campan Mihaela , Laird Peter W. , Tangrea Joseph , Johnson Laura Lee , Schatzkin Arthur , Lanza Elaine 
Published: September 2005

Abstract
Hypermethylation of tumor suppressor and other regulatory genes is thought to play an important role in colorectal neoplasia and tumorigenesis. This study examined the association between gene methylation status in baseline adenomas and subsequent adenoma recurrence in a randomized dietary intervention study, the Polyp Prevention Trial. The methylation status of four genes [CDKN2A (p16), PTGS2 (COX2), ESR1 (ER-α), and PGR(PR)] was determined by MethyLight in 284 baseline adenomas from 196 trial participants. The association of gene methylation with recurrence was determined using logistic regression models. Gene methylation was evaluated as percent of methylated reference, a measure of methylation of each gene relative to control DNA. ESR1methylation status was inversely associated with adenoma recurrence, odds ratio = 0.36 (95% confidence interval, 0.15-0.88; P = 0.02) for the highest compared with the lowest quartile of the ESR1methylation. Further, ESR1 methylation status was inversely associated with the recurrence of multiple adenomas, advanced adenomas, and the recurrence of adenomas in the proximal but not distal bowel. No association between CDKN2A, PTGS2, or PGR methylation and adenoma recurrence was observed. These data suggest that ESR1 methylation may play a role in subsequent adenoma recurrence.
Residential Herbicide Use and Risk of Non-Hodgkin Lymphoma
Authors: Hartge Patricia , Colt Joanne S. , Severson Richard K. , Cerhan James R. , Cozen Wendy , Camann David , Zahm Shelia Hoar , Davis Scott 
Published: September 2005

Abstract
Context: Environmental exposure to herbicides has been hypothesized to contribute to the long-term increase in non-Hodgkin lymphoma (NHL).
Objective: To estimate the effects of residential herbicide exposure on NHL risk.
Design: Population-based case-control study.
Setting: Iowa and metropolitan Detroit, Los Angeles, and Seattle, 1998 to 2000.
Participants: NHL patients ages 20 to 74 years and unaffected residents identified by random digit dialing and Medicare eligibility files.
Main Outcome Measures: Computer-assisted personal interviews (1,321 cases, 1,057 controls) elicited data on herbicide use at each home occupied since 1970. Levels of 2,4-dichlorophenoxy-acetic acid and dicamba were measured in dust taken from used vacuum cleaner bags in the current home (679 cases, 510 controls who had owned at least half of their carpets for ≥5 years).
Results: Herbicide use on the lawn or garden was similar among cases and controls (adjusted relative risk, 1.02; 95% confidence interval, 0.84-1.23). Estimated risk did not increase with greater duration, frequency, or total number of applications of herbicides to the lawn, the garden, or to both combined. Risk was not elevated for respondents who applied the herbicides themselves and not for those exposed during the 1970s, 1980s, or 1990s. We detected 2,4-dichlorophenoxy-acetic acid equally often in homes of cases and controls (78%). We found dicamba in homes of 15% of cases and 20% of controls. We also found no elevation in risk among the respondents who had the highest dust levels and highest self-reported exposures. We found no consistent patterns for specific histologies.
Conclusions: We found no detectable excess associated with residential exposures. Residential herbicide exposures are unlikely to explain the long-term increase in NHL.
Risk of Testicular Germ Cell Cancer in Relation to Variation in Maternal and Offspring CytochromeP450 Genes Involved in Catechol Estrogen Metabolism
Authors: Starr Jacqueline R. , Chen Chu , Doody David R. , Hsu Li , Ricks Sherianne , Weiss Noel S. , Schwartz Stephen M. 
Published: September 2005

AbstractThe incidence of testicular germ cell carcinoma (TGCC) is highest among men ages 20 to 44 years. Exposure to relatively high circulating maternal estrogen levels during pregnancy has long been suspected as being a risk factor for TGCC. Catechol (hydroxylated) estrogens have carcinogenic potential, thought to arise from reactive catechol intermediates with enhanced capability of forming mutation-inducing DNA adducts. Polymorphisms in maternal or offspring genes encoding estrogen-metabolizing enzymes may influence prenatal catechol estrogen levels and could therefore be biomarkers of TGCC risk. We conducted a population-based, case-parent triad study to evaluate TGCC risk in relation to maternal and/or offspring polymorphisms in CYP1A2, CYP1B1, CYP3A4, and CYP3A5. We identified 18- to 44-year-old men diagnosed with invasive TGCC from 1999 to 2004 through a population-based cancer registry in Washington State and recruited cases and their parents (110 case-parent triads, 50 case-parent dyads). Maternal or offspring carriage of CYP1A2 −163A was associated with reduced risk of TGCC [maternal heterozygote relative risk (RR), 0.6; 95% confidence interval (95% CI), 0.2-1.7; offspring heterozygote RR, 0.7; 95% CI, 0.3-1.5)]. Maternal CYP1B1 48Gly homozygosity was associated with a 2.7-fold increased risk of TGCC (95% CI, 0.9-7.9), with little evidence that Leu432Val or Asn453Ser genotypes were related to risk. Men were also at increased risk of TGCC if they carried the CYP3A4 −392G (RR, 7.0; 95% CI, 1.6-31) or CYP3A5 6986G (RR, 2.4; 95% CI, 1.1-5.6) alleles. These results support the hypothesis that maternal and/or offspring catechol estrogen activity may influence sons' risk of TGCC.
Acquisition and Persistence of Human Papillomavirus Infection in Younger Men: A Prospective Follow-up Study among Danish Soldiers
Authors: Kjaer Susanne Krüger , Munk Christian , Falck Winther Jeanette , Jørgensen Hans Ole , Meijer Chris J.L.M. , van den Brule Adriaan J.C. 
Published: September 2005

Abstract
No data is yet available on incidence or persistence of human papillomavirus (HPV) infection in men. We enrolled 374 younger male conscripts (18-29 years) in a prospective study, and they were examined twice with an interval of 6 to 8 months. Data collection included a questionnaire and a sample of cells from the penis for HPV detection using PCR. In addition, the presence of Chlamydia trachomatis DNA was assessed in urine samples by means of PCR.
The HPV prevalence at the first and second examinations was 33.8% and 31.9%, respectively. The acquisition rate of HPV (overall) during follow-up was 13.8%, and nearly one fourth of the participants were HPV positive at both examinations. Number of sex partners during follow-up was the most important risk factor for acquiring HPV (odds ratio, 17.2; 95% confidence interval, 4.6-64.7, for ≥3 partners versus ≤1 partner). In contrast, acquisition of a new HPV type in initially HPV-positive men was strongly related to having multiple HPV types at enrollment (OR, 4.1; 95% confidence interval, 1.4-12.3). This was also the most important risk factor for HPV persistence together with current smoking and having a high-risk HPV type at enrollment. This is the first study to assess risk factors for acquisition and persistence of HPV. The sexually transmitted nature of the infection is confirmed, and the data point to an important role of having multiple HPV types for persistence.
Prenatal and Perinatal Correlates of Adult Mammographic Breast Density
Authors: Cerhan James R. , Sellers Thomas A. , Janney Carol A. , Pankratz V. Shane , Brandt Kathy R. , Vachon Celine M. 
Published: September 2005

Abstract
Background: Adult mammographic percent density is one of the strongest known risk factors for breast cancer. In utero exposure to high levels of endogenous estrogens (or other pregnancy hormones) has been hypothesized to increase breast cancer risk in later life. We examined the hypothesis that those factors associated with higher levels of estrogen during pregnancy or shortly after birth are associated with higher mammographic breast density in adulthood.
Methods: We analyzed data on 1,893 women from 360 families in the Minnesota Breast Cancer Family Study who had screening mammograms, risk factor data, over age 40, and no history of breast cancer. Prenatal and perinatal risk factor data were ascertained using a mailed questionnaire. Mammographic percent density and dense area were estimated from the mediolateral oblique view using Cumulus, a computer-assisted thresholding program. Linear mixed effects models incorporating familial correlation were used to assess the association of risk factors with percent density, adjusting for age, weight, and other breast cancer risk factors, all at time of mammography.
Results: The mean age at mammography was 60.4 years (range, 40-91 years), and 76% were postmenopausal. Among postmenopausal women, there was a positive association of birthweight with percent density (P trend &lt;0.01), with an adjusted mean percent density of 17.1% for &lt;2.95 kg versus 21.0% for ≥3.75 kg. There were suggestive positive associations with gestational age (mean percent density of 16.7% for preterm birth, 20.2% for term birth, and 23.0% for late birth; P trend = 0.07), maternal eclampsia/preeclampsia (mean percent density of 19.9% for no and 14.6% for yes; P = 0.16), and being breast-fed as an infant (mean percent density of 18.2% for never and 20.0% for ever; P = 0.08). There was no association of percent density with maternal age, birth order, maternal use of alcohol or cigarettes, or neonatal jaundice. Except for being breast-fed, these associations showed similar but attenuated trends among premenopausal women, although none were statistically significant. The results for dense area paralleled the percent density results. The associations of gestational age and being breast-fed as an infant with percent density attenuated when included in the same model as birthweight.
Conclusions: Birthweight was positively associated with mammographic breast density and dense area among postmenopausal women and more weakly among premenopausal women, suggesting that it may be a marker of this early life exposure. These results offer some support to the hypothesis that pregnancy estrogens or other pregnancy changes may play a role in breast cancer etiology, and suggest that these factors may act in part through long-term effects on breast density.
Physical Activity and the Risk of Prostate Cancer in The Netherlands Cohort Study, Results after 9.3 Years of Follow-up
Authors: Zeegers Maurice P.A. , Dirx Miranda J.M. , van den Brandt Piet A. 
Published: September 2005

Abstract
Background: The aim of the current study was to evaluate the relation between physical activity and prostate cancer risk with specific emphasis on interaction with body mass index (BMI) and baseline energy intake.
Methods: The association between prostate cancer and physical activity was evaluated in the Netherlands Cohort Study, conducted among 58,279 men ages 55 to 69 years at entry. Information regarding baseline nonoccupational physical activity, history of sports participation, and occupational physical activity was collected with a questionnaire in 1986. After 9.3 years, 1,386 incident prostate cancer cases were available for case-cohort analyses. Multivariate incidence rate ratios (RR) and corresponding 95% confidence intervals (95% CI) were calculated using Cox regression analyses.
Results: Neither baseline nonoccupational physical activity (RR, 1.01; 95% CI, 0.81-1.25 for &gt;90 versus &lt;30 minutes per day), history of sports participation (RR, 1.04; 95% CI, 0.90-1.22 for ever versus never participated), nor occupational physical activity (RR, 0.91; 95% CI, 0.70-1.18 for &gt;12 versus &lt;8 KJ/min energy expenditure in the longest held job) showed an inverse relation with prostate cancer risk. We found an increased risk of prostate cancer for men who were physically active for &gt;1 hour per day in obese men (BMI &gt; 30) and men with a high baseline energy intake.
Discussion: The results of this current study do not support the hypothesis that physical activity protects against prostate cancer in men.
The E211 G&gt;A Androgen Receptor Polymorphism Is Associated with a Decreased Risk of Metastatic Prostate Cancer and Androgenetic Alopecia
Authors: Hayes Vanessa M. , Severi Gianluca , Eggleton Sarah A. , Padilla Emma J.D. , Southey Melissa C. , Sutherland Robert L. , Hopper John L. , Giles Graham G. 
Published: September 2005

Abstract
The androgen receptor (AR) gene encodes a transcription factor, which mediates androgen action in target tissues, including the prostate. Prostate cancer is androgen dependent, implicating AR in susceptibility to this male condition. Male pattern balding, androgenetic alopecia, has recently been associated with prostate cancer, suggesting shared androgen pathways. The CAG and GGC repeats in the AR have been studied extensively as markers of prostate cancer susceptibility, with inconclusive findings, whereas the AR-E211 G&gt;A polymorphism has been associated with androgenetic alopecia. We assessed the repeat linked single nucleotide polymorphism as a marker of risk association in prostate cancer, including androgenetic alopecia, in an Australian population-based case-control study. In 815 prostate cancer cases and 719 controls, the proportion of A-allele carriers was the same in each group. Overall, there was no evidence for an association between the A allele and risk of prostate cancer, however, the proportion of A-allele carriers in metastatic prostate cancer (5%) was lower than in less advanced disease (16%, P = 0.03). The proportion of A-allele carriers was 24% in nonbald men but it was lower in men with vertex alopecia alone (13%, P = 0.001) or in combination with frontal alopecia (7%, P &lt; 0.0001). This inverse association between the A allele and baldness was independent of prostate cancer status (P for interaction = 0.2). These results suggest that the AR-E211 A allele, in linkage with the functional repeat sequences, is associated with a lower risk of metastatic prostate cancer and a lower risk of alopecia.
The Biology ofHelicobacter pyloriInfection, a Major Risk Factor for Gastric Adenocarcinoma
Authors: Pinto-Santini Delia , Salama Nina R. 
Published: September 2005

AbstractHelicobacter pylori infection of the human stomach is the most important risk factor for development of gastric cancer. Whereas persistent viral infection leads to a number of cancers, H. pylori was the first bacteria linked to a human cancer. The exact mechanisms that lead to cancer induction are not clear, but study of the bacterial factors important for colonization and the host responses to the infection are starting to yield important clues.
Serrated Adenomas Have a Pattern of Genetic Alterations That Distinguishes Them from Other Colorectal Polyps
Authors: Yashiro Masakazu , Laghi Luigi , Saito Koji , Carethers John M. , Slezak Premysl , Rubio Carlos , Hirakawa Kosei , Boland C. Richard 
Published: September 2005

Abstract
Background: Serrated adenomas are characterized by serrated crypts with dysplasia, and are distinguished from other polyps by their histology, but the genetic basis of serrated adenomas is unknown. We investigated genetic alterations in colorectal polyps to determine if a specific pattern were associated with serrated adenomas.
Methods: Sixty-six small (&lt;10 mm) colorectal polyps were studied, including 11 hyperplastic polyps, 27 serrated adenomas, 9 tubular adenomas, 6 tubulovillous adenomas, and 3 villous adenomas. Allelic imbalance and microsatellite instability were detected by analysis of microsatellites on 5q, 18q, 17p, 2p, and 3p; K-ras mutations were detected by oligonucleotide hybridization.
Results: Each polyp subset had its own characteristic mutational signature. Allelic imbalance of 18q was significantly more common (P &lt; 0.05), whereas allelic imbalance of 5q and K-ras mutations were significantly less common (P &lt; 0.05) in serrated adenomas compared with other polyps. Allelic imbalance of 17p was not found in any polyp.
Conclusions: Serrated adenomas are significantly more likely to have allelic imbalance at 18q than other types of adenomas, and significantly less likely to have allelic imbalance at 5q or K-ras mutations. Serrated adenomas seem to evolve through a different genetic pathway than other types of polyps in the colon.
Semiquantitative Human Papillomavirus Type 16 Viral Load and the Prospective Risk of Cervical Precancer and Cancer
Authors: Castle Philip E. , Schiffman Mark , Scott David R. , Sherman Mark E. , Glass Andrew G. , Rush Brenda B. , Schussler John E. , Wacholder Sholom , Lorincz Attila T. 
Published: September 2005

Abstract
We examined whether higher human papillomavirus type 16 (HPV16) viral load predicted risk of cervical intraepithelial neoplasia 3 (CIN3) or cancer (together termed ≥CIN3) within a cohort of 20,810 women followed for 10 years with cytologic screening. Semiquantitative viral load for HPV16 was measured on baseline cervicovaginal specimens using a type-specific hybridization probe test with signal amplification. An increased risk of ≥CIN3 associated with higher HPV16 viral load was found only among cytologically negative women in early follow-up, suggesting that these cases were related to the detection of prevalent lesions missed at baseline. Women with higher HPV16 viral load were more likely to undergo ablative treatment during follow-up than those with lower viral load (Ptrend = 0.008), possibly diminishing any additional risk for ≥CIN3 attributable to higher HPV16 viral loads.
Common Polymorphisms inERCC2(Xeroderma pigmentosumD) are not Associated with Breast Cancer Risk
Authors: Kuschel Bettina , Chenevix-Trench Georgia , Spurdle Amanda B. , Chen Xiaoqing , Hopper John L. , Giles Graham G. , McCredie Margret , Chang-Claude Jenny , Gregory Catherine S. , Day Nick E. , Easton Douglas F. , Ponder Bruce A.J. , Dunning Alison M. , Pharoah Paul D.P. 
Published: September 2005

AbstractA substantial proportion of the familial risk of breast cancer may be due to genetic variants, each contributing a small effect. The protein encoded by ERCC2 is a key enzyme involved in nucleotide excision repair, in which gene defects could lead to cancer prone syndromes such as Xeroderma pigmentosum D. We have examined the association between single nucleotide polymorphisms in the ERCC2 gene and the incidence of invasive breast cancer in three case-control series, with a maximum of 3,634 patients and of 3,340 controls. None of the three single nucleotide polymorphisms were significantly associated with the incidence of breast cancer.
Human Papillomavirus Genotype Distribution in Low-Grade Cervical Lesions: Comparison by Geographic Region and with Cervical Cancer
Authors: Clifford Gary M. , Rana Rashida K. , Franceschi Silvia , Smith Jennifer S. , Gough Gerald , Pimenta Jeanne M. 
Published: September 2005

Abstract
Low-grade squamous intraepithelial lesions (LSIL) associated with certain human papillomavirus (HPV) genotypes may preferentially progress to cervical cancer. HPV genotyping may thus have the potential to improve the effectiveness of screening programs and to reduce overtreatment. LSIL cases (n = 8,308) from 55 published studies were included in a meta-analysis. HPV genotype distribution was assessed by geographic region and in comparison with published data on cervical squamous cell carcinoma (SCC). HPV detection in LSIL was 80% in North America but less than 70% in other regions, most likely reflecting regional differences in LSIL diagnosis. Among 5,910 HPV-positive LSILs, HPV16 was the most common genotype (26.3%) followed by HPV31 (11.5%), HPV51 (10.6%), and HPV53 (10.2%). HPV-positive LSILs from Africa were 2-fold less likely to be infected with HPV16 than those in Europe, and HPV-positive LSILs from North America were more likely to be infected with HPV18 than those from Europe or South/Central America. Interpretation for rarer genotypes was hampered by variation in HPV testing methodology. SCC/LSIL prevalence ratios indicated that HPV16 was 2-fold and HPV18 was 1.5-fold more common in SCC than in HPV-positive LSIL, thus appearing more likely to progress than other high-risk genotypes (SCC/LSIL prevalence ratios between 0.05 and 0.85). HPV53 and HPV66 showed SCC/LSIL ratios of 0.02 and 0.01, respectively. HPV genotype distribution in LSIL differs from that in cervical cancer, highlighting the importance of HPV genotype in the risk of progression from LSIL to malignancy. Some regional differences in the relative importance of HPV genotypes in LSIL were noted.