bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming Growth Factor-β (TGF-β)–Inducible Gene TMEPAI Converts TGF-β from a Tumor Suppressor to a Tumor Promoter in Breast Cancer
Authors: Singha Prajjal K. , Yeh I-Tien , Venkatachalam Manjeri A. , Saikumar Pothana 
Published: July 2010

Abstract
TMEPAI is a transforming growth factor-β (TGF-β)–induced transmembrane protein that is overexpressed in several cancers. How TMEPAI expression relates to malignancy is unknown. Here, we report high expression of TMEPAI in estrogen receptor/progesterone receptor–negative and human epidermal growth factor receptor-2–negative breast cancer cell lines and primary breast cancers that was further increased by TGF-β treatment. Basal and TGF-β–induced expression of TMEPAI were inhibited by the TGF-β receptor antagonist SB431542 and overexpression of Smad7 or a dominant-negative mutant of Alk-5. TMEPAI knockdown attenuated TGF-β–induced growth and motility in breast cancer cells, suggesting a role for TMEPAI in growth promotion and invasiveness. Further, TMEPAI knockdown decreased breast tumor mass in a mouse xenograft model in a manner associated with increased expression of phosphatase and tensin homologue (PTEN) and diminished phosphorylation of Akt. Consistent with the effects through the phosphatidylinositol 3-kinase pathway, tumors with TMEPAI knockdown exhibited elevated levels of the cell cycle inhibitor p27kip1 and attenuated levels of DNA replication and expression of hypoxia-inducible fator 1α and vascular endothelial growth factor. Together, these results suggest that TMEPAI functions in breast cancer as a molecular switch that converts TGF-β from a tumor suppressor to a tumor promoter. Cancer Res; 70(15); 6377–83. ©2010 AACR.
Comparison of Measurements of Human Papillomavirus Persistence for Postcolposcopic Surveillance for Cervical Precancerous Lesions
Authors: Gage Julia C. , Schiffman Mark , Solomon Diane , Wheeler Cosette M. , Castle Philip E. 
Published: July 2010

Abstract
Objective: Following guidelines, women evaluated by colposcopy, but not found to have a precancerous lesion, could be tested again at 12 months for carcinogenic human papillomavirus (HPV). Compared with pooled-probe testing, measuring HPV genotype–specific persistence might better predict subsequent grade 3 cervical intraepithelial neoplasia (CIN3).
Methods: For women enrolled in the immediate colposcopy arm of the Atypical squamous cells of undetermined significance (ASCUS) and Low-grade squamous intraepithelial lesion (LSIL) Triage Study (ALTS), who underwent enrollment colposcopy but were without prevalently detected CIN2 or worse (CIN2+; n = 671), we compared 1-year HPV persistence, as measured by a pooled HPV genotype test (hybrid capture 2; hc2) versus a research PCR HPV genotyping test (line blot assay; LBA) as predictors of “missed prevalent” or possibly incident CIN3 diagnosed between 12 and 24 months.
Results: Thirty-two (4.8%) women were diagnosed with subsequent CIN3. Testing repeatedly hc2-positive (hc2+) was more common (49.0%) than genotype-specific persistence as detected by LBA (30.3%, P &lt; 0.01). Although absolute risks of CIN3 following repeat hc2+ or genotype-specific persistence were similar (8.8% versus 8.4%, P = 0.86), repeat hc2+ was more sensitive for identifying CIN3 than genotype-specific persistence (90.6% versus 53.1%, P &lt; 0.01). Among 329 women repeatedly hc2+, women with persistent HPV16 were at higher risk of CIN3 than non–HPV16-persistent women (23.1% versus 7.0%, P &lt; 0.01).
Conclusions: For postcolposcopy management, 1-year HPV persistence as measured by hc2 would recall more women but was more sensitive and similarly predictive for CIN3 in the following year than detection of genotype-specific persistence by LBA.
Impact: Although find little utility for measuring type-specific persistence, testing for persistent HPV16 might be clinically useful. Cancer Epidemiol Biomarkers Prev; 19(7); 1668–74. ©2010 AACR.
Genetic Variation in TYMS in the One-Carbon Transfer Pathway Is Associated with Ovarian Carcinoma Types in the Ovarian Cancer Association Consortium
Authors: Kelemen Linda E. , Goodman Marc T. , McGuire Valerie , Rossing Mary Anne , Webb Penelope M. , Köbel Martin , Anton-Culver Hoda , Beesley Jonathan , Berchuck Andrew , Brar Sony , Carney Michael E. , Chang-Claude Jenny , Chenevix-Trench Georgia , Cramer Daniel W. , Cunningham Julie M. , DiCioccio Richard A. , Doherty Jennifer A. , Easton Douglas F. , Fredericksen Zachary S. , Fridley Brooke L. , Gates Margaret A. , Gayther Simon A. , Gentry-Maharaj Aleksandra , Høgdall Estrid , Kjær Susanne Krüger , Lurie Galina , Menon Usha , Moorman Patricia G. , Moysich Kirsten , Ness Roberta B. , Palmieri Rachel T. , Pearce Celeste L. , Pharoah Paul D.P. , Ramus Susan J. , Song Honglin , Stram Daniel O. , Tworoger Shelley S. , Van Den Berg David , Vierkant Robert A. , Wang-Gohrke Shan , Whittemore Alice S. , Wilkens Lynne R. , Wu Anna H. , Schildkraut Joellen M. , Sellers Thomas A. , Goode Ellen L. 
Published: July 2010

Abstract
Background: We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample of assembled cases to investigate associations by histologic type.
Methods: Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and study site.
Results: The five polymorphisms were not associated with ovarian carcinoma overall (Ptrend &gt; 0.13); however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; Pheterogeneity = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05).
Conclusions: TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification.
Impact: Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology. Cancer Epidemiol Biomarkers Prev; 19(7); 1822–30. ©2010 AACR.
Increased Cancer Predisposition in Family Members of Colorectal Cancer Patients Harboring the p.V600E BRAF Mutation: a Population-Based Study
Authors: Wish Tyler A. , Hyde Angela J. , Parfrey Patrick S. , Green Jane S. , Younghusband H. Banfield , Simms Michelle I. , Fontaine Dan G. , Dicks Elizabeth L. , Stuckless Susan N. , Gallinger Steven , McLaughlin John R. , Woods Michael O. , Green Roger C. 
Published: July 2010

Abstract
Background: The serrated pathway represents a distinct molecular pathway of colorectal carcinogenesis and is associated with the p.V600E BRAF mutation. The objective of this study is to characterize the cancer family history and clinicopathologic features of colorectal cancer (CRC) patients according to the microsatellite instability (MSI) and BRAF mutation status of their tumors.
Methods: The tumors from 558 population-based CRC patients underwent pathologic examination and molecular analysis for MSI, BRAF, and germline mutations in mismatch repair genes MUTYH and APC. The cancer history in first-degree relatives (FDR) of index patients was ascertained.
Results: The risk of CRC in FDRs of index patients with MSI-H BRAF mutation [hazard ratio (HR) = 2.49; 95% confidence interval (95% CI), 1.57- 3.93] and microsatellite-stable BRAF mutation tumors (HR = 1.64; 95% CI, 1.01-2.66) was significantly elevated compared with FDRs of index patients with microsatellite-stable BRAF wild-type tumors. The incidence of nonmelanoma skin cancer was also significantly elevated in FDRs of patients with BRAF mutation CRC (HR = 2.52; 95% CI, 1.31-4.86). Furthermore, BRAF mutation CRC was associated with a distinct clinical, molecular, and pathologic phenotype.
Conclusions: The increased incidence of cancer in FDRs of index CRC patients with the p.V600E BRAF mutation may be explained by a genetic predisposition to develop cancer through the serrated pathway of colorectal carcinogenesis.
Impact: Family members of BRAF CRC patients have an increased predisposition to develop cancer. Future work should aim to identify the causative genetic factors. Cancer Epidemiol Biomarkers Prev; 19(7); 1831–9. ©2010 AACR.
Association between Genetic Variants in the 8q24 Cancer Risk Regions and Circulating Levels of Androgens and Sex Hormone–Binding Globulin
Authors: Chu Lisa W. , Meyer Tamra E. , Li Qizhai , Menashe Idan , Yu Kai , Rosenberg Philip S. , Huang Wen-Yi , Quraishi Sabah M. , Kaaks Rudolf , Weiss Jocelyn M. , Hayes Richard B. , Chanock Stephen J. , Hsing Ann W. 
Published: July 2010

Abstract
Background: Genome-wide association studies have identified multiple independent regions on chromosome 8q24 that are associated with cancers of the prostate, breast, colon, and bladder.
Methods: To investigate their biological basis, we examined the possible association between 164 single nucleotide polymorphisms (SNPs) in the 8q24 risk regions spanning 128,101,433-128,828,043 bp, and serum androgen (testosterone, androstenedione, 3αdiol G, and bioavailable testosterone), and sex hormone–binding globulin levels in 563 healthy, non-Hispanic, Caucasian men (55-74 years old) from a prospective cohort study (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial). Age-adjusted linear regression models were used to determine the association between the SNPs in an additive genetic model and log-transformed biomarker levels.
Results: Three adjacent SNPs centromeric to prostate cancer risk-region 2 (rs12334903, rs1456310, and rs980171) were associated with testosterone (P &lt; 1.1 × 10−3) and bioavailable testosterone (P &lt; 6.3 × 10−4). Suggestive associations were seen for a cluster of nine SNPs in prostate cancer risk region 1 and androstenedione (P &lt; 0.05).
Conclusions: These preliminary findings require confirmation in larger studies but raise the intriguing hypothesis that genetic variations in the 8q24 cancer risk regions might correlate with androgen levels.
Impact: These results might provide some clues for the strong link between 8q24 and prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 19(7); 1848–54. ©2010 AACR.
Urine Accurately Reflects Circulating Isoflavonoids and Ascertains Compliance During Soy Intervention
Authors: Franke Adrian A. , Hebshi Sandra M. , Pagano Ian , Kono Naoko , Mack Wendy J. , Hodis Howard N. 
Published: July 2010

AbstractBackground: Isoflavonoids (IFL) may protect against chronic diseases, including cancer. IFL exposure is traditionally measured from plasma (PL), but the reliability of urine is uncertain. We assessed whether IFL excretion in overnight urine (OU) or spot urine (SU) reliably reflects IFLs in PL and the usefulness of the three matrices to determine soy intake compliance.Methods: In a randomized, double-blind, placebo-controlled soy intervention trial with 350 postmenopausal women, IFLs (daidzein, genistein, glycitein, equol, O-desmethylangolensin, dihydrodaidzein, dihydrogenistein) were analyzed by liquid chromatography/mass spectrometry in OU, SU, and PL collected at baseline and every 6 months over 2.5 years.Results: High between-subject intraclass correlations between all three matrices (median, 0.94) and high between-subject Pearson correlations (median rOU-PL = 0.80; median rSU-PL = 0.80; median rOU-SU = 0.92) allowed the development of equations to predict IFL values from any of the three matrices. Equations developed from a randomly selected 87% of all available data were valid because high correlations were found on the residual 13% of data between equation-generated and measured IFL values (median rOU-PL = 0.86; median rSU-PL = 0.78; median rOU-SU = 0.84); median absolute IFL differences for OU-PL, SU-PL, and OU-SU were 8.8 nmol/L, 10.3 nmol/L, and 0.28 nmol/mg, respectively. All three matrices showed highly significant IFL differences between the placebo and soy intervention group at study end (P &lt; 0.0001) and highly significant correlations between IFL values and counted soy doses in the intervention group.Conclusions: OU and SU IFL excretion reflect circulating PL IFL levels in healthy postmenopausal women accurately.Impact: Noninvasively-collected urine can be used to reliably determine systemic IFL exposure and soy intake compliance. Cancer Epidemiol Biomarkers Prev; 19(7); 1775–83. ©2010 AACR.
TP53 Arg72Pro Polymorphism and Colorectal Cancer Risk: A Systematic Review and Meta-Analysis
Authors: Dahabreh Issa J. , Linardou Helena , Bouzika Peggy , Varvarigou Vasileia , Murray Samuel 
Published: July 2010

Abstract
Background: The TP53 rs1042522 polymorphism (c.215C&gt;G, Arg72Pro) has been extensively investigated as a potential risk factor for colorectal cancer, but the results have thus far been inconclusive.
Methods: We searched multiple electronic databases to identify studies investigating the association between the Arg72Pro polymorphism and colorectal cancer. Individual study odds ratios (OR) and their confidence intervals were estimated using allele-frequency, recessive, and dominant genetic models. Summary ORs where estimated using random effects models.
Results: We identified 23 eligible case-control studies, investigating 6,514 cases and 9,334 controls. There was significant between-study heterogeneity for all genetic models. The control group in one of the studies was not in Hardy-Weinberg equilibrium; only three studies reported that genotyping was blinded to case/control status and five studies used tumor tissue for case genotyping. Overall, we did not identify any association between rs1042522 and colorectal cancer risk under an allele-frequency comparison (OR, 0.99; 95% confidence interval, 0.89–1.09). Likewise, no association was evident under dominant or recessive models. Studies using tumor tissue for case genotyping found a protective effect for the Pro allele, compared with studies using somatic DNA (Pinteraction = 0.03). Results were also inconsistent between different genotyping methods (Pinteraction = 0.03).
Conclusion: We did not identify an association between TP53 rs1042522 and colorectal cancer. Published results seem to be driven by technical artifacts rather than true biological effects.
Impact: Future genetic association studies should use more rigorous genotyping methods and avoid the use of tumor tissue as a source of DNA to prevent genotype misclassification due to loss of heterozygosity. Cancer Epidemiol Biomarkers Prev; 19(7); 1840–7. ©2010 AACR.
Inherited Variations in AR, ESR1, and ESR2 Genes Are Not Associated With Prostate Cancer Aggressiveness or With Efficacy of Androgen Deprivation Therapy
Authors: Sun Tong , Lee Gwo-Shu Mary , Werner Lillian , Pomerantz Mark , Oh William K. , Kantoff Philip W. , Freedman Matthew L. 
Published: July 2010

Abstract
Background: Sex steroid hormone receptors mediate essential processes in normal prostate growth and contribute to prostate cancer development.
Method: In this study, we investigated the association between common inherited variation of the AR, ESR1, and ESR2 genes and two clinically relevant traits: the risk of developing aggressive prostate cancer and the response to androgen deprivation therapy (ADT) in a hospital-based cohort. A total of 43 tagging single nucleotide polymorphisms covering the loci of AR (n = 4), ESR1 (n = 32), and ESR2 (n = 7) were successfully genotyped in 4,073 prostate cancer cases.
Results: None of these single nucleotide polymorphisms were significantly associated with disease aggressiveness as assessed by the D'Amico risk classification, pathologic stage, or the response to ADT.
Conclusions: Our results suggest that common genetic variations in AR, ESR1, or ESR2 are not strongly associated with prostate cancer aggressiveness or response to ADT.
Impact: Our study did not find convincing evidence of inherited variations in the major receptors for androgens and estrogens and their associations with prostate cancer traits. Cancer Epidemiol Biomarkers Prev; 19(7); 1871–8. ©2010 AACR.
Human Papillomavirus Genotypes in Cervical Intraepithelial Neoplasia Grade 3
Authors: Castle Philip E. , Schiffman Mark , Wheeler Cosette M. , Wentzensen Nicolas , Gravitt Patti E. 
Published: July 2010

Abstract
Background: There are few large case series describing the human papillomavirus (HPV) genotypes found in women diagnosed with rigorously reviewed cervical intraepithelial neoplasia grade 3 (CIN3), cervical precancer.
Methods: The Atypical Squamous Cells of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study (ALTS) was a clinical trial to evaluate the best management strategies for women with equivocal (ASCUS) or mildly abnormal (LSIL) Pap tests. During enrollment and the 2-year follow-up, 608 women had a histopathologic diagnosis of CIN3 and PCR-based HPV genotyping results on cervical specimens. The genotyping results were ranked hierarchically according to cancer risk: HPV16 &gt; other carcinogenic HPV &gt; noncarcinogenic HPV &gt; PCR negative.
Results: Among the 608 women diagnosed with CIN3, 601 (98.8%) cases were positive for any HPV genotype and 95.4% for any carcinogenic HPV. HPV16 (59.9%), HPV31 (18.1%), HPV52 (14.8%), HPV51 (14.0%), and HPV18 (13.2%) were the five most common HPV genotypes detected. Younger age, consensus histologic confirmation, smoking, and multiparity increased the likelihood of testing HPV 16 positive. Specifically, HPV16-positive CIN3 occurred at a younger age than CIN3 positive for other carcinogenic HPV genotypes (median of 23.5 years versus 25 years, respectively; P = 0.0003, Kruskal-Wallis).
Conclusions: HPV16-positive CIN3 was more commonly diagnosed in younger women (versus older women), with consensus diagnosis (versus some disagreement between reviewers), and in smokers (versus nonsmokers), and was less commonly diagnosed in multiparous women compared CIN3 positive for other carcinogenic HPV genotypes.
Impact: In populations vaccinated against HPV16 (and HPV18), the median age of CIN3 in women with ASCUS and LSIL cytology should shift to older ages, possibly permitting later age at first screening. Cancer Epidemiol Biomarkers Prev; 19(7); 1675–81. ©2010 AACR.
No Association between TERT-CLPTM1L Single Nucleotide Polymorphism rs401681 and Mean Telomere Length or Cancer Risk
Authors: Pooley Karen A. , Tyrer Jonathan , Shah Mitul , Driver Kristy E. , Leyland Jean , Brown Judith , Audley Tina , McGuffog Lesley , Ponder Bruce A.J. , Pharoah Paul D.P. , Easton Douglas F. , Dunning Alison M. 
Published: July 2010

Abstract
Background: A recent study reported genetic variants in the TERT-CLPTM1L locus that were associated with mean telomere length, and with risk of multiple cancers.
Methods: We evaluated the association between single nucleotide polymorphism (SNP) rs401681 (C &gt; T) and mean telomere length, using quantitative real-time PCR, in blood-extracted DNA collected from 11,314 cancer-free participants from the Sisters in Breast Screening study, the Melanoma and Pigmented Lesions Evaluative Study melanoma family study, and the SEARCH Breast, Colorectal, Melanoma studies. We also examined the relationship between rs401618 genotype and susceptibility to breast cancer (6,800 cases and 6,608 controls), colorectal cancer (2,259 cases and 2,181 controls), and melanoma (787 cases and 999 controls).
Results: The “per T allele” change in mean telomere length (ΔCt), adjusted for age, study plate, gender, and family was 0.001 [95% confidence intervals (CI), 0.01-0.02; P trend = 0.61]. The “per T allele” odds ratio for each cancer was 1.01 for breast cancer (95% CI, 0.96-1.06; P trend = 0.64), 1.02 for colorectal cancer (95% CI, 0.94-1.11; P trend = 0.66), and 0.99 for melanoma (95% CI, 0.84-1.15; P trend = 0.87).
Conclusions: We found no evidence that this SNP was associated with mean telomere length, or with risk of breast cancer, colorectal cancer, or melanoma.
Impact: Our results indicate that the observed associations between rs401681 and several cancer types might be weaker than previously described. The lack of an association in our study between this SNP and mean telomere length suggests that any association with cancer risk at this locus is not mediated through TERT. Cancer Epidemiol Biomarkers Prev; 19(7); 1862-5. ©2010 AACR.
Specialty Supplements and Breast Cancer Risk in the VITamins And Lifestyle (VITAL) Cohort
Authors: Brasky Theodore M. , Lampe Johanna W. , Potter John D. , Patterson Ruth E. , White Emily 
Published: July 2010

Abstract
Background: Use of nonvitamin, nonmineral “specialty” supplements has increased substantially over recent decades. Several supplements may have anti-inflammatory or anticancer properties. Additionally, supplements taken for symptoms of menopause have been associated with reduced risk of breast cancer in two case-control studies. However, there have been no prospective studies of the association between the long-term use of these supplements and breast cancer risk.
Methods: Participants were female members of the VITamins And Lifestyle (VITAL) Cohort. Postmenopausal women, ages 50 to 76 years, who were residents of western Washington State, completed a 24-page baseline questionnaire in 2000 to 2002 (n = 35,016). Participants were queried on their recency (current versus past), frequency (days/week), and duration (years) of specialty supplement use. Incident invasive breast cancers (n = 880) from 2000 to 2007 were obtained from the Surveillance, Epidemiology, and End Results registry. Multivariable-adjusted hazards ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazards models.
Results: Current use of fish oil was associated with reduced risk of breast cancer (HR, 0.68; 95% CI, 0.50-0.92). Ten-year average use was suggestive of reduced risk (P trend = 0.09). These results held for ductal but not lobular cancers. The remaining specialty supplements were not associated with breast cancer risk: Specifically, use of supplements sometimes taken for menopausal symptoms (black cohosh, dong quai, soy, or St. John's wort) was not associated with risk.
Conclusions: Fish oil may be inversely associated with breast cancer risk.
Impact: Fish oil is a potential candidate for chemoprevention studies. Until that time, it is not recommended for individual use for breast cancer prevention. Cancer Epidemiol Biomarkers Prev; 19(7); 1696–708. ©2010 AACR.