bluuebunny/crossref_metadata_2025 huggingface dataset:
MUPP1 complexes renal K+channels to alter cell surface expression and whole cell currents
Authors: Sindic Aleksandra , Huang Chunfa , Chen An-Ping , Ding Yaxian , Miller-Little William A. , Che Danian , Romero Michael F. , Miller R. Tyler
Published: May 2009

We previously found that the Ca2+-sensing receptor (CaR) interacts with and inactivates the inwardly rectifying K+channel Kir4.2 that is expressed in the kidney cortex and that has a COOH-terminal PDZ domain. To identify potential scaffolding proteins that could organize a macromolecular signaling complex involving the CaR and Kir4.2, we used yeast two-hybrid cloning with the COOH-terminal 125 amino acids (AA) of Kir4.2 as bait to screen a human kidney cDNA library. We identified two independent partial cDNAs corresponding to the COOH-terminal 900 AA of MUPP1, a protein containing 13 PDZ binding domains that is expressed in the kidney in tight junctions and lateral borders of epithelial cells. When expressed in human embryonic kidney (HEK)-293 cells, Kir4.2 coimmunoprecipitates reciprocally with MUPP1 but not with a Kir4.2 construct lacking the four COOH-terminal amino acids, Kir5.1, or the CaR. MUPP1 and Kir4.2 coimmunoprecipitate reciprocally from rat kidney cortex extracts. Coexpression of MUPP1 with Kir4.2 in HEK-293 cells leads to reduced cell surface expression of Kir4.2 as assessed by cell surface biotinylation. Coexpression of MUPP1 and Kir4.2 in Xenopus oocytes results in reduced whole cell currents compared with expression of Kir4.2 alone, whereas expression of Kir4.2ΔPDZ results in minimal currents and is not affected by coexpression with MUPP1. Immunofluorescence studies of oocytes demonstrate that MUPP1 reduces Kir4.2 membrane localization. These results indicate that Kir4.2 interacts selectively with MUPP1 to affect its cell surface expression. Thus MUPP1 and Kir4.2 may participate in a protein complex in the nephron that could regulate transport of K+as well as other ions.
Early brain swelling in acute hypoxia
Authors: Dubowitz David J. , Dyer Edward A. W. , Theilmann Rebecca J. , Buxton Richard B. , Hopkins Susan R.
Published: May 2009

Acute mountain sickness (AMS) and high-altitude cerebral edema share common clinical characteristics, suggesting cerebral swelling may be an important factor in the pathophysiology of AMS. Hypoxia and hypocapnia associated with high altitude are known to exert strong effects on the control of the cerebral circulation, yet how these effects interact during acute hypoxia, and whether AMS-susceptible subjects may have a unique response, is still unclear. To test if self-identified AMS-susceptible individuals show altered brain swelling in response to acute hypoxia, we used quantitative arterial spin-labeling and volumetric MRI to measure cerebral blood flow and cerebrospinal fluid (CSF) volume changes during 40 min of acute hypoxia. We estimated changes in cerebral blood volume (CBV) (from changes in cerebral blood flow) and brain parenchyma swelling (from changes in CBV and CSF). Subjects with extensive high-altitude experience in two groups participated: self-identified AMS-susceptible ( n = 6), who invariably experienced AMS at altitude, and self-identified AMS-resistant ( n = 6), who almost never experienced symptoms. During 40-min hypoxia, intracranial CSF volume decreased significantly [−10.5 ml (SD 6.9), P < 0.001]. There were significant increases in CBV [+2.3 ml (SD 2.5), P < 0.005] and brain parenchyma volume [+8.2 ml (SD 6.4), P < 0.001]. However, there was no significant difference between self-identified AMS-susceptible and AMS-resistant groups for these acute-phase changes. In acute hypoxia, brain swelling occurs earlier than previously described, with significant shifts in intracranial CSF occurring as early as 40 min after exposure. These acute-phase changes are present in all individuals, irrespective of susceptibility to AMS.
The Consequences of Short-Range Stiffness and Fluctuating Muscle Activity for Proprioception of Postural Joint Rotations: The Relevance to Human Standing
Authors: Loram Ian D. , Lakie Martin , Di Giulio Irene , Maganaris Constantinos N.
Published: May 2009

Proprioception comes from muscles and tendons. Tendon compliance, muscle stiffness, and fluctuating activity complicate transduction of joint rotation to a proprioceptive signal. These problems are acute in postural regulation because of tiny joint rotations and substantial short-range muscle stiffness. When studying locomotion or perturbed balance these problems are less applicable. We recently measured short-range stiffness in standing and considered the implications for load stability. Here, using an appropriately simplified model we analyze the conversion of joint rotation to spindle input and tendon tension while considering the effect of short-range stiffness, tendon compliance, fluctuating muscle activity, and fusimotor activity. Basic principles determine that when muscle stiffness and tendon compliance are high, fluctuating muscle activity is the greatest factor confounding registration of postural movements, such as ankle rotations during standing. Passive and isoactive muscle, uncomplicated by active length fluctuations, enable much better registration of joint rotation and require fewer spindles. Short-range muscle stiffness is a degrading factor for spindle input and enhancing factor for Golgi input. Constant fusimotor activity does not enhance spindle registration of postural joint rotations in actively modulated muscle: spindle input remains more strongly associated with muscle activity than joint rotation. A hypothesized rigid α–γ linkage could remove this association with activity but would require large numbers of spindles in active postural muscles. Using microneurography, the existence of a rigid α–γ linkage could be identified from the correlation between spindle output and muscle activity. Basic principles predict a proprioceptive “dead zone” in the active agonist muscle that is related to the short-range muscle stiffness.
Tolerance to Sedative/Hypnotic Actions of GABAergic Drugs Correlates With Tolerance to Potentiation of Extrasynaptic Tonic Currents of Alcohol-Dependent Rats
Authors: Liang Jing , Spigelman Igor , Olsen Richard W.
Published: May 2009

Alcohol tolerance resulting from chronic administration is well known to be accompanied by cross-tolerance to sedative/anesthetic drugs, especially those acting on the γ-aminobutyric acid type A receptors (GABAARs). Rats treated with chronic intermittent ethanol (CIE) show decreased function and altered pharmacology of GABAARs in hippocampal neurons, consistent with cell- and location-specific changes in GABAAR subunit composition. We previously observed variably altered sensitivity to GABAergic drugs in vivo and in hippocampal neurons using whole cell patch-clamp recording in brain slices. Here, we examined additional clinical GABAergic drugs to correlate CIE-induced tolerance to potentiation of neuronal GABAAR-mediated currents with tolerance of these agents to sedative/anesthetic effects in vivo. Typical of several drug classes and two cell types, in CA1 pyramidal neurons, the benzodiazepine diazepam doubled the total charge transfer (TCT) of miniature postsynaptic inhibitory currents (mIPSCs), whereas it quadrupled the TCT of tonic currents. CIE treatment altered these responses to variable extent, as it did to loss of righting reflex (LORR) induced by these same drugs: 90–95% tolerance to flurazepam, the neuroactive steroid alphaxalone, and ethanol; 30–40% to pentobarbital, etomidate, and the GABA agonist gaboxadol; and no tolerance to propofol. There was a strong correlation between tolerance in the LORR assay and tolerance to enhancement of tonic currents, but not mIPSCs. The striking correlation suggests that the sedative/anesthetic actions of GABAergic drugs may be mediated primarily via the potentiation of extrasynaptic GABAARs. This requires the reasonable assumption that the same types of GABAARs in other brain regions involved directly in hypnotic drug actions show similar tolerance.
Proteinase-Activated Receptor-1 Activation Presynaptically Enhances Spontaneous Glutamatergic Excitatory Transmission in Adult Rat Substantia Gelatinosa Neurons
Authors: Fujita T. , Liu T. , Nakatsuka T. , Kumamoto E.
Published: May 2009

Proteinase-activated receptors (PARs) have a unique activation mechanism in that a proteolytically exposed N-terminal region acts as a tethered ligand. A potential impact of PAR on sensory processing has not been fully examined yet. Here we report that synthetic peptides with sequences corresponding to PAR ligands enhance glutamatergic excitatory transmission in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by using the whole cell patch-clamp technique. The frequency of spontaneous excitatory postsynaptic current (EPSC) was increased by PAR-1 agonist SFLLRN-NH2(by 47% at 1 μM) with small increases by PAR-2 and -4 agonists (SLIGKV-NH2and GYPGQV-OH, respectively; at >3 μM); there was no change in its amplitude or in holding current at −70 mV. The PAR-1 peptide action was inhibited by PAR-1 antagonist YFLLRNP-OH. TFLLR-NH2, an agonist which is more selective to PAR-1 than SFLLRN-NH2, dose-dependently increased spontaneous EPSC frequency (EC50= 0.32 μM). A similar presynaptic effect was produced by PAR-1 activating proteinase thrombin in a manner sensitive to YFLLRNP-OH. The PAR-1 peptide action was resistant to tetrodotoxin and inhibited in Ca2+-free solution. Primary-afferent monosynaptically evoked EPSC amplitudes were unaffected by PAR-1 agonist. These results indicate that PAR-1 activation increases the spontaneous release of l-glutamate onto SG neurons from nerve terminals in a manner dependent on extracellular Ca2+. Considering that sensory processing within the SG plays a pivotal role in regulating nociceptive transmission to the spinal dorsal horn, the PAR-1-mediated glutamatergic transmission enhancement could be involved in a positive modulation of nociceptive transmission.
Perforin Expression in Peripheral Blood Lymphatic Cells of Patients Subjected to Laparoscopic or Open Cholecystectomy
Authors: Grbas Harry , Mrakovčić-Šutić Ines , Depolo Arsen , Radošević-Stašić Biserka
Published: May 2009

Perforin-(P-) related characteristics of cytotoxic T lymphocytes and natural killer cells were investigated in peripheral blood of patients subjected to open (OC;n=23) or laparoscopic cholecystectomy (LC;n=21) and healthy controls (n=20). Blood samples were obtained preoperatively and 24 hours after the surgeries, and the data were correlated with the intensity of cholestasis and concomitant inflammation, determined by functional hepatic tests. Postoperative differences were found to be minimal: OC decreased only the percentage ofCD56+cells, while LC decreased the fraction ofCD8+P+cells and augmented the mean fluorescence intensity of P in CD56 cells. Patients elected for OC had, however, higher preoperative numbers of totalP+,CD3+P+, andCD4+P+cells than patients elected for LC and healthy controls, while both groups of patients, preoperatively, had lower fraction ofCD16+P+andCD56+P+cells. These changes were in high correlation with blood concentrations of CRP, AP, and ALT, emphasizing the link between the preoperative cholestasis and inflammation and P-dependent cytotoxic mechanisms.
Colorimetric Analysis on Flocculation of Bioinspired Au Self‐Assembly for Biophotonic Application
Authors: Kim Wan-Joong , Seo JaeTae , Ah Chil Seong , Austin Jasmine , Kim Shanghee , Kim Ansoon , Sung Gun Yong , Yun Wan Soo
Published: May 2009

Gold nanoparticles exhibited strong surface plasmon absorption and couplings between neighboring particles within bioactivated self‐assembly modified their optical properties. Colorimetric analysis on the optical modification
of surface plasmon resoanance (SPR) shift and flocculation parameter functionalized bioinspired gold assembly for biophotonic application. The physical origin of bioinspired gold aggregation‐induced shifting, decreasing, or broadening of the plasmon absorption spectra could be explained in terms of dynamic depolarization, collisional damping, and shadowing effects.
Electron Microscopy and Optical Characterization of Cadmium Sulphide Nanocrystals Deposited on the Patterned Surface of Diatom Biosilica
Authors: Gutu Timothy , Gale Debra K. , Jeffryes Clayton , Wang Wei , Chang Chih-hung , Rorrer Gregory L. , Jiao Jun
Published: May 2009

Intricately patterned biosilica obtained from the shell of unicellular algae called diatoms serve as novel templates for fabrication of optoelectronic nanostructures. In this study, the surface of diatom frustules that possessed hierarchical architecture ordered at the micro and nanoscale was coated with a nanostructured polycrystalline cadmium sulphide (CdS) thin film using a chemical bath deposition technique. The CdS thin film was composed of spherical nanoparticles with a diameter of about 75 nm. The CdS nanoparticle thin film imparted new photoluminescent properties to the intricately patterned diatom nanostructure. The imparted photoluminescent properties were dependent on the CdS coverage onto the frustules surface. The intrinsic photoluminescent properties of the frustules were strongly quenched by the deposited CdS. The origin of PL spectra was discussed on the basis of the band theory and native defects.
Risk Factors for Pituitary Tumors: A Case-control Study
Authors: Schoemaker Minouk J. , Swerdlow Anthony J.
Published: May 2009

Pituitary gland tumors are usually benign but are associated with substantial morbidity. Their etiology is largely unknown. We conducted a population-based case-control study of potential risk factors for pituitary tumors in Southeast England. Information on medical and reproductive history, female sex hormones, and cigarette smoking was collected by personal interview from 299 cases and 630 controls aged 18 to 59 years. Tumor risk was reduced in subjects reporting a past diagnosis of hay fever [odds ratio (OR), 0.7; 95% confidence interval (CI), 0.5-1.0] but not asthma or eczema. Risk was raised in women who were postmenopausal 1 year before diagnosis (OR, 3.2; 95% CI, 1.6-6.2), especially if menopause was surgically induced (OR, 6.7; 95% CI, 2.2-19.9) or occurred under age 40 years (OR, 7.5; 95% CI, 2.6-21.4). This effect remained when evaluating menopausal status 10 years before diagnosis. There was no association with parity overall, but risk was increased for first childbirth under age 20 years compared with nulliparity (OR, 3.4; 95% CI, 1.4-8.4). No significant association was observed with ever use of oral contraceptives or hormone replacement therapy, nor with cigarette smoking, past head injury, past diagnosis with epilepsy, or birth characteristics, except for an inverse association of risk with maternal age. This study suggests a raised risk of pituitary tumors in relation to surgically induced menopause, early postmenopausal age, and young age at childbirth, and possibly a reduced risk with hay fever and increasing maternal age. Reasons for these associations need further investigation, but some associations might be due to hormonal effects of an undiagnosed pituitary tumor. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1492–500)
Association of Diabetes and Body Mass Index with Levels of Prostate-Specific Antigen: Implications for Correction of Prostate-Specific Antigen Cutoff Values?
Authors: Müller Heiko , Raum Elke , Rothenbacher Dietrich , Stegmaier Christa , Brenner Hermann
Published: May 2009

Background: In a recent study, an inverse association between diabetes and prostate-specific antigen (PSA) levels was observed, and several studies reported lower PSA levels in groups with higher body mass index. However, all of the studies were conducted in populations with intensive PSA screening and the role of diabetes severity, duration, and therapy are yet to be explored.

Methods: Associations of diabetes duration and treatment, hemoglobin A1c, and BMI with PSA levels were assessed among 778 men ages 50 to 74 years, randomly chosen from the 2000 to 2002 baseline recruitment of a large population-based cohort study in Germany (prevalence of diabetes, 17%), using linear regression analyses.

Results: PSA values were significantly reduced in men with insulin treatment (−39%; P = 0.006) and oral diabetic medication (−24%; P = 0.030), and in men with elevated (6.1-6.9%) and highly (≥7%) elevated hemoglobin A1c values (−15%, P = 0.004 and −29%, P = 0.003, respectively). PSA reduction was not associated with duration of diabetes. Obesity was possibly associated with a reduction of PSA levels (−14%; P = 0.096).

Conclusions: Our study suggests that more severe forms of diabetes are associated with lower PSA levels and confirms the magnitude of reduction in PSA levels in diabetic men overall. The observed PSA reduction parallels reported risk reduction of prostate cancer among diabetic men. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1350–6)
Common Genetic Variation in TP53 and Risk of Human Papillomavirus Persistence and Progression to CIN3/Cancer Revisited
Authors: Koshiol Jill , Hildesheim Allan , Gonzalez Paula , Bratti M. Concepcion , Porras Carolina , Schiffman Mark , Herrero Rolando , Rodriguez Ana C. , Wacholder Sholom , Yeager Meredith , Chanock Stephen J. , Burk Robert D. , Wang Sophia S.
Published: May 2009

Driven by findings that human papillomavirus (HPV)-induced degradation of p53 differs by a TP53 polymorphism at codon 72 (Pro72Arg), past studies of TP53 genetic variants and cervical cancer have focused on this nonsynonymous polymorphism, with mixed results. We analyzed common single nucleotide polymorphisms (SNP) across the TP53 locus in a population-based nested case-control study in Guanacaste, Costa Rica. We evaluated 11 SNPs, including Pro72Arg (rs1042522), among 1,281 women: 465 with cervical intraepithelial neoplasia grade 3/cancer (CIN3+), 380 with HPV persistence (median, 25 months), and 436 random population controls. We combined HPV persistence and CIN3+ into one case group because they did not differ in TP53 genotypic frequencies and calculated odds ratios and 95% confidence intervals (CI) for individual SNPs and inferred haplotypes. We observed that proline at codon 72 was associated with increased risk of CIN3+/persistence compared with population controls. Relative to GG (Arg), the CG (Pro/Arg) and CC (Pro) genotypes had a 1.3-fold (95% CI, 0.99-1.6) and 1.8-fold (95% CI, 1.2-2.7) increased risk, respectively (Ptrend < 0.01). rs12951053 and rs1642785 were also associated with CIN3+/persistence (P trend, 0.05 and 0.04, respectively), as was a haplotype containing the codon 72 variant (rs1042522), rs12951053, rs1642785, and rs12947788 (odds ratio, 1.6; 95% CI, 1.1-2.3 versus the most common haplotype, which comprised the major alleles for all 11 SNPs). Although genetic variation in TP53 might affect the natural history of HPV and cervical cancer, further work is needed to elucidate the possible mechanism. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1631–7)
Genetic Polymorphisms in the Catechol Estrogen Metabolism Pathway and Breast Cancer Risk
Authors: Reding Kerryn W. , Weiss Noel S. , Chen Chu , Li Christopher I. , Carlson Christopher S. , Wilkerson Hui-Wen , Farin Federico M. , Thummel Kenneth E. , Daling Janet R. , Malone Kathleen E.
Published: May 2009

Background: This study investigated whether single nucleotide polymorphisms (SNP) in genes within the catechol estrogen metabolism pathway altered the risk of breast cancer alone or in combination, as well as whether menopausal hormone therapy modified the effect of these SNPs on breast cancer risk.

Methods: In a population-based case-control study of breast cancer, 891 cases and 878 controls were genotyped for six functional SNPs in the COMT, CYP1B1, GSTM1, GSTP1, and GSTT1 genes.

Results: Women homozygous with the T allele in CYP1B1*2 (Ser119; rs1056827) were at 1.69 (95% confidence interval, 1.17-2.46) times the risk of women homozygous with the G allele; women homozygous with the G allele in GSTP1 (Val105; rs1695) were at 0.73 (95% confidence interval, 0.54-0.99) times the risk of breast cancer compared with women homozygous with the A allele. No other SNPs tested were associated with breast cancer to any appreciable degree. Potential gene-gene and gene-hormone therapy interactions were investigated.

Conclusion: With the exception of GSTP1 and possibly CYP1B1*2, our findings do not provide support for the role of genetic variation in the catechol estrogen metabolism pathway and breast cancer risk in postmenopausal women. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1461–7)
Higher Prevalence of Secretory CSE1L/CAS in Sera of Patients with Metastatic Cancer
Authors: Tung Min-Che , Tsai Chin-Shaw Stella , Tung Jai-Nien , Tsao Tang-Yi , Chen Hung-Chang , Yeh Kun-Tu , Liao Ching-Fong , Jiang Ming-Chung
Published: May 2009

Metastatic markers are highly useful diagnostic and prognostic indicators of cancer metastasis. Herein, we report that secretory CSE1L/CAS, a cellular apoptosis susceptibility protein, is a new marker for metastatic cancer. CAS was colocalized with matrix metalloproteinase-2 in vesicles surrounding the outside of MCF-7 cell membranes, and the COOH-terminal domain of CAS was associated with matrix metalloproteinase-2-containing vesicles. Immunohistochemical staining for CAS was positive in the stroma and gland lumens of human metastatic cancer tissues. CAS was also detected in conditioned medium from B16-F10 melanoma cells and more frequently in the sera of patients with metastatic cancer than in sera from patients with primary cancer. Specifically, the prevalence of serum CAS in serum samples from 146 patients was 58.2% (32 of 55), 32.0% (8 of 25), and 12.1% (8 of 66) for patients with metastatic, invasive, and primary cancers, respectively. Our results suggest that CAS is a secretory protein associated with cancer metastasis, which may have clinical utility in metastatic cancer screening and diagnosis. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1570–7)
Reproductive and Hormonal Risk Factors for Ductal Carcinoma In situ of the Breast
Authors: Phillips Lynette S. , Millikan Robert C. , Schroeder Jane C. , Barnholtz-Sloan Jill S. , Levine Beverly J.
Published: May 2009

One-fifth of all newly diagnosed breast cancer cases are ductal carcinoma in situ (DCIS), but little is known about DCIS risk factors. Recent studies suggest that some subtypes of DCIS (high grade or comedo) share histopathologic and epidemiologic characteristics with invasive disease, whereas others (medium or low grade or non-comedo) show different patterns. To investigate whether reproductive and hormonal risk factors differ among comedo and non-comedo types of DCIS and invasive breast cancer (IBC), we used a population-based case-control study of 1,808 invasive and 446 DCIS breast cancer cases and their age and race frequency-matched controls (1,564 invasive and 458 DCIS). Three or more full-term pregnancies showed a strong inverse association with comedo-type DCIS [odds ratio (OR), 0.53; 95% confidence interval (95% CI), 0.30-0.95] and a weaker inverse association for non-comedo DCIS (OR, 0.73; 95% CI, 0.42-1.27). Several risk factors (age at first full-term pregnancy, breast-feeding, and age at menopause) showed similar associations for comedo-type DCIS and IBC but different associations for non-comedo DCIS. Ten or more years of oral contraceptive showed a positive association with comedo-type DCIS (OR, 1.31; 95% CI, 0.70-2.47) and IBC (OR, 2.33; 95% CI, 1.06-5.09) but an inverse association for non-comedo DCIS (OR, 0.51; 95% CI, 0.25-1.04). Our results support the theory that comedo-type DCIS may share hormonal and reproductive risk factors with IBC, whereas the etiology of non-comedo DCIS deserves further investigation. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1507–14)
Influence of Ovarian Cancer Risk Status on the Diagnostic Performance of the Serum Biomarkers Mesothelin, HE4, and CA125
Authors: Shah Chirag A. , Lowe Kimberly A. , Paley Pamela , Wallace Erin , Anderson Garnet L. , McIntosh Martin W. , Andersen M. Robyn , Scholler Nathalie , Bergan Lindsay A. , Thorpe Jason D. , Urban Nicole , Drescher Charles W.
Published: May 2009

Objective: To evaluate the effect of ovarian cancer risk on the performance of the serum biomarkers mesothelin, human epididymis protein 4 (HE4), and CA125.

Methods: We measured mesothelin, HE4, and CA125 levels from women with invasive ovarian cancer (n = 143), benign gynecologic conditions (n = 124), and controls (n = 344). Demographic, epidemiologic, reproductive, medical, and family history data were collected using a standardized questionnaire. Pedigree and BRCA 1/2 test results were used to stratify women into average and high-risk groups. The diagnostic accuracy of each biomarker was characterized using receiver operating characteristic curve methods.

Results: Baseline characteristics did not vary by risk or case status. The distribution of stage and histology was similar in average and high-risk women. All three markers discriminated ovarian cancer cases from risk-matched healthy and benign controls. Marker performance did not vary by risk status. The sensitivity at 95% specificity for discriminating cases from risk-matched healthy control women in the average and high-risk groups, respectively, was 53.9% and 39.0% for mesothelin, 80.4% and 87.8% for HE4, and 79.4% and 82.9% for CA125. The performance of the markers was not as robust when cases were compared with benign controls. Area under the curve values for cases versus healthy and benign controls did not vary by risk status.

Conclusions: The ability of serum mesothelin, HE4, and CA 125 levels to discriminate ovarian cancer cases from healthy and benign controls is not influenced by risk status. Our findings support the pursuit of additional studies evaluating the early detection potential of these markers in high-risk populations. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1365–72)
Muscular Strength and Adiposity as Predictors of Adulthood Cancer Mortality in Men
Authors: Ruiz Jonatan R. , Sui Xuemei , Lobelo Felipe , Lee Duck-chul , Morrow James R. , Jackson Allen W. , Hébert James R. , Matthews Charles E. , Sjöström Michael , Blair Steven N.
Published: May 2009

Background: We examined the associations between muscular strength, markers of overall and central adiposity, and cancer mortality in men.

Methods: A prospective cohort study including 8,677 men ages 20 to 82 years followed from 1980 to 2003. Participants were enrolled in The Aerobics Centre Longitudinal Study, the Cooper Institute in Dallas, Texas. Muscular strength was quantified by combining 1-repetition maximal measures for leg and bench presses. Adiposity was assessed by body mass index (BMI), percent body fat, and waist circumference.

Results: Cancer death rates per 10,000 person-years adjusted for age and examination year were 17.5, 11.0, and 10.3 across incremental thirds of muscular strength (P = 0.001); 10.9, 13.4, and 20.1 across BMI groups of 18.5-24.9, 25.0-29.9, and ≥30 kg/m2, respectively (P = 0.008); 11.6 and 17.5 for normal (<25%) and high percent body fat (≥25%), respectively (P = 0.006); and 12.2 and 16.7 for normal (≤102 cm) and high waist circumference (>102 cm), respectively (P = 0.06). After adjusting for additional potential confounders, hazard ratios (95% confidence intervals) were 1.00 (reference), 0.65 (0.47-0.90), and 0.61 (0.44-0.85) across incremental thirds of muscular strength, respectively (P = 0.003 for linear trend). Further adjustment for BMI, percent body fat, waist circumference, or cardiorespiratory fitness had little effect on the association. The associations of BMI, percent body fat, or waist circumference with cancer mortality did not persist after further adjusting for muscular strength (all P ≥ 0.1).

Conclusions: Higher levels of muscular strength are associated with lower cancer mortality risk in men, independent of clinically established measures of overall and central adiposity, and other potential confounders. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1468–76)
Prospective Study of JC Virus Seroreactivity and the Development of Colorectal Cancers and Adenomas
Authors: Rollison Dana E. , Helzlsouer Kathy J. , Lee Ji-Hyun , Fulp William , Clipp Sandra , Hoffman-Bolton Judy A. , Giuliano Anna R. , Platz Elizabeth A. , Viscidi Raphael P.
Published: May 2009

Background: Infection with JC virus has been proposed as a risk factor for colorectal cancer. A nested case-control study was conducted to evaluate the association between prediagnostic JC virus antibodies and the risk of incident colorectal cancer and adenomas.

Methods: Two research serum banks were established in Washington County, MD in 1974 and 1989, with the collection of blood samples from >45,000 volunteers. Incident colorectal cancer cases diagnosed through 2006 (n = 611) were identified among participants by linkage to population-based cancer registries, contributing 729 pairs of observations. Cases of adenomatous polyps (n = 123) were identified from participants of the 1989 cohort who reported having a colonoscopy-detected adenoma at follow-up through 2000 with histology confirmed through medical record review. One control was matched to each case on age, sex, race, and date of blood draw, and, for adenoma controls, date of endoscopy. IgG antibodies to JC virus were measured using virus-like particle ELISA. Associations between JC virus seropositivity and colorectal cancer and adenomas were estimated using conditional logistic regression.

Results: Overall, there was no association between antibodies to JC virus and colorectal cancer [odds ratio (OR), 0.91; 95% confidence interval (95% CI), 0.71-1.17]. However, a statistically significant positive association between JC virus seropositivity and subsequent adenoma diagnosis was observed among males (OR, 2.31; 95% CI, 1.20-4.46), whereas a statistically significant inverse association was observed among females (OR, 0.31; 95% CI, 0.14-0.67; P for interaction = 0.01), after adjustment for baseline smoking and body mass index.

Conclusions: Overall, JC virus seropositivity was not associated with colorectal cancer development up to 31 years later. Future studies are needed to confirm the adenoma findings. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1515–23)
Dietary Acrylamide Intake and Brain Cancer Risk
Authors: Hogervorst Janneke G.F. , Schouten Leo J. , Konings Erik J.M. , Goldbohm R. Alexandra , van den Brandt Piet A.
Published: May 2009

Background: Acrylamide is a probable human carcinogen, which is present in several heat-treated foods. In epidemiologic studies, positive associations with endometrial, ovarian, and renal cell cancer risk have been observed. The incidence of central nervous system tumors was increased upon acrylamide administration in drinking water to rats. In the current study, the association between dietary acrylamide intake and human brain cancer risk was investigated for the first time.

Methods: In 1986, 120,852 persons (ages 55-69 years) were included in the Netherlands Cohort Study on diet and cancer. At baseline, a random subcohort of 5,000 participants was randomly selected from the total cohort for a case-cohort approach. Acrylamide intake was assessed with a food frequency questionnaire at baseline and based on acrylamide analyses in relevant Dutch foods. Hazard ratios (HR) were calculated using Cox proportional hazards analysis. Subgroup analyses were done for microscopically verified brain cancer, astrocytic gliomas, high-grade astrocytic gliomas, and never-smokers. The acrylamide risk estimates were adjusted for possible brain cancer risk factors.

Results: After 16.3 years of follow-up, 216 brain cancer cases were available for analysis. The multivariable-adjusted HR per 10 μg/d increment of acrylamide intake was 1.02 (95% confidence interval, 0.89-1.16). HRs were not significantly increased either when dietary acrylamide intake was analyzed as a categorical variable. Also, there was no association in the subgroups based on histology and smoking.

Conclusion: In this prospective cohort study, acrylamide intake was not associated with brain cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1663–6)
Reproductive History and Pancreatic Cancer Incidence and Mortality in a Cohort of Postmenopausal Women
Authors: Stevens Richard J. , Roddam Andrew W. , Green Jane , Pirie Kirstin , Bull Diana , Reeves Gillian K. , Beral Valerie ,   on behalf of the Million Women Study Collaborators
Published: May 2009

There is inconsistent evidence about the effect of reproductive history on women's risk of pancreatic cancer. In the Million Women Study, a prospective cohort of middle-aged women in the United Kingdom, we examined associations between reproductive history and pancreatic cancer incidence and mortality, controlling for age, socioeconomic status, geographic region, body mass index, smoking, and history of diabetes. During 7.1 million person-years of follow-up in 995,192 postmenopausal women, there were 1,182 incident pancreatic cancers. Pancreatic cancer incidence and mortality did not vary significantly with age at menarche, number of children, age at first birth, breast-feeding, type of menopause, age at menopause, or time since menopause. Any effect of reproductive history and pancreatic cancer risk in women is likely to be weak, if it exists at all. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1457–60)
Established Prostate Cancer Susceptibility Variants are not Associated with Disease Outcome
Authors: Wiklund Fredrik E. , Adami Hans-Olov , Zheng Sigun L. , Stattin Pär , Isaacs William B. , Grönberg Henrik , Xu Jianfeng
Published: May 2009

Recent genome-wide association studies have been successful in identifying common sequence variants associated with prostate cancer risk; however, their importance in prostate cancer prognosis remains unknown. To assess confirmed prostate cancer susceptibility variants with prostate cancer prognosis, we genotyped 16 established susceptibility variants in a Swedish cohort of 2,875 prostate cancer cases, ascertained between 2001 and 2003, with complete follow-up regarding vital status through January 2008. Cox regression models, adjusted for age, clinical stage, pathologic grade, nodal or distant metastases, and diagnostic serum levels of prostate-specific antigen level, were used to assess association between risk variants and prostate cancer–specific survival. During follow-up, 626 men died, and of those, 440 had prostate cancer classified as their underlying cause of death. We found no association between any of the explored sequence variants and prostate cancer–specific mortality, either in exploring individual variants or in assessing the cumulative effect of all variants. We conclude that hitherto established prostate cancer susceptibility variants are not associated with the lethal potential of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1659–62)
A Study of Amplicor Human Papillomavirus DNA Detection in the Atypical Squamous Cells of Undetermined Significance–Low-Grade Squamous Intraepithelial Lesion Triage Study
Authors: Wentzensen Nicolas , Gravitt Patti E. , Solomon Diane , Wheeler Cosette M. , Castle Philip E.
Published: May 2009

We analyzed the performance of Amplicor for detecting carcinogenic human papillomavirus (HPV) infections and cervical precancer in women with an atypical squamous cells of undetermined significance (ASCUS) Pap and compared the results with Hybrid Capture 2 (hc2) in the ASCUS and low-grade squamous intraepithelial lesion (LSIL) triage study (ALTS). Baseline specimens collected from women referred into ALTS based on an ASCUS Pap result were prospectively tested by hc2 and retrospectively tested by Amplicor (n = 3,277). Following receiver-operator-characteristics curve analysis, Amplicor performance was analyzed at three cutoffs (0.2, 1.0, and 1.5). Paired Amplicor and hc2 results were compared for the detection of 2-year cumulative cervical intraepithelial neoplasia (CIN) grade 3 and more severe disease outcomes (CIN3+) and for the detection of 13 targeted carcinogenic HPV types. Amplicor at the 0.2 cutoff had a higher sensitivity for the detection of CIN3+ (95.8% versus 92.6%, P = 0.01) but a much lower specificity (38.9% versus 50.6%, P < 0.001) than hc2. Amplicor at the 1.5 cutoff had an identical sensitivity for the detection of CIN3+ (92.6%) and a slightly lower specificity (47.5%; P < 0.001). The positive predictive value of hc2 was higher at all Amplicor cutoffs, whereas referral rates were significantly lower (53.2% for hc2 versus 64.1% at the 0.2 cutoff and 56.0% at the 1.5 cutoff, P < 0.001). Amplicor was more analytically specific for detecting targeted carcinogenic HPV types than hc2. Amplicor at the 1.5 cutoff had comparable performance with hc2. Whereas Amplicor missed more disease related to nontargeted types, hc2 was more likely to miss disease related to targeted types. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1341–9)
Physical Activity as a Determinant of Fecal Bile Acid Levels
Authors: Wertheim Betsy C. , Martínez María Elena , Ashbeck Erin L. , Roe Denise J. , Jacobs Elizabeth T. , Alberts David S. , Thompson Patricia A.
Published: May 2009

Physical activity is protective against colon cancer, whereas colonic bile acid exposure is a suspected risk factor. Although likely related, the association between physical activity and bile acid levels has not been well-studied. Furthermore, the effect of triglycerides, which are known to modify bile acid levels, on this relationship has not been investigated. We conducted a cross-sectional analysis of baseline fecal bile acid levels for 735 colorectal adenoma formers obtained from participants in a phase III ursodeoxycholic acid chemoprevention trial. Compared with the lowest quartile of recreational physical activity duration, the highest quartile was associated with a 17% lower fecal bile acid concentration, adjusted for age, sex, dietary fiber intake, and body mass index (P = 0.042). Furthermore, consistent with a previously established relationship between serum triglyceride levels and bile acid metabolism, we stratified by triglyceride level and observed a 34% lower fecal bile acid concentration (highest versus lowest quartiles of physical activity) in individuals with low triglycerides (<136 mg/dL; P = 0.002). In contrast, no association between physical activity and fecal bile acid concentration was observed for subjects with high triglycerides (≥136 mg/dL). Our results suggest that the biological mechanism responsible for the protective effect of physical activity on the incidence of colon cancer may be partially mediated by decreasing colonic bile acid exposure. However, this effect may be limited to individuals with lower triglyceride levels. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1591–8)
One-Carbon Metabolism and Prostate Cancer Risk: Prospective Investigation of Seven Circulating B Vitamins and Metabolites
Authors: Johansson Mattias , Van Guelpen Bethany , Vollset Stein Emil , Hultdin Johan , Bergh Anders , Key Tim , Midttun Øivind , Hallmans Göran , Ueland Per M. , Stattin Pär
Published: May 2009

Purpose: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before.

Materials and Methods: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression.

Results: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; Ptrend = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; Ptrend = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; Ptrend = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk.

Conclusion: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1538–43)
Colorectal Cancer in Relation to Postmenopausal Estrogen and Estrogen Plus Progestin in the Women's Health Initiative Clinical Trial and Observational Study
Authors: Prentice Ross L. , Pettinger Mary , Beresford Shirley A.A. , Wactawski-Wende Jean , Hubbell F. Allan , Stefanick Marcia L. , Chlebowski Rowan T.
Published: May 2009

Background: Colorectal cancer incidence was reduced among women assigned to active treatment in the Women's Health Initiative (WHI) estrogen plus progestin-randomized trial, but the interpretation was obscured by an associated later stage of diagnosis. In contrast, the estrogen-alone trial showed no incidence reduction or differential stage at diagnosis. Here, data from the WHI observational study are considered, in conjunction with colorectal cancer mortality data from the hormone therapy trials, in an attempt to clarify postmenopausal hormone therapy effects.

Participants and Methods: Postmenopausal women ages 50 to 79 years at WHI enrollment. Estrogen-alone analyses include 21,552 and 10,739 women who were posthysterectomy from the observational study and clinical trial, respectively. Estrogen plus progestin analyses include 32,084 and 16,608 observational study and clinical trial women with uterus. Colorectal cancers were verified by central medical and pathology report review.

Results: Hazard ratios (95% confidence intervals) from the WHI observational study were 0.80 (0.53-1.20) for estrogen and 1.15 (0.74-1.79) for estrogen plus progestin, with, respectively, 168 and 175 women diagnosed with colorectal cancer. Delayed diagnosis with estrogen plus progestin is not evident in the observational study. No protective effect on colorectal cancer mortality in the estrogen plus progestin trial is seen over an 8-year intervention and follow-up period.

Conclusion: Hazard ratio patterns in the WHI clinical trial and observational study do not provide strong evidence of a clinically important colorectal cancer benefit with either estrogen-alone or estrogen plus progestin over 7 to 8 years of treatment and follow-up. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1531–7)
Genetic Polymorphisms in Nitric Oxide Synthase Genes Modify the Relationship between Vegetable and Fruit Intake and Risk of Non-Hodgkin Lymphoma
Authors: Han Xuesong , Zheng Tongzhang , Lan Qing , Zhang Yaqun , Kilfoy Briseis A. , Qin Qin , Rothman Nathaniel , Zahm Shelia H. , Holford Theodore R. , Leaderer Brian , Zhang Yawei
Published: May 2009

Oxidative damage caused by reactive oxygen species and other free radicals is involved in carcinogenesis. It has been suggested that high vegetable and fruit intake may reduce the risk of non-Hodgkin lymphoma (NHL) as vegetables and fruit are rich in antioxidants. The aim of this study is to evaluate the interaction of vegetable and fruit intake with genetic polymorphisms in oxidative stress pathway genes and NHL risk. This hypothesis was investigated in a population-based case-control study of NHL and NHL histologic subtypes in women from Connecticut, including 513 histologically confirmed incident cases and 591 randomly selected controls. Gene-vegetable/fruit joint effects were estimated using unconditional logistic regression model. The false discovery rate method was applied to adjust for multiple comparisons. Significant interactions with vegetable and fruit intake were mainly found for genetic polymorphisms on nitric oxide synthase (NOS) genes among those with diffuse large B-cell lymphoma and follicular lymphoma. Two single nucleotide polymorphisms in the NOS1 gene were found to significantly modify the association between total vegetable and fruit intake and risk of NHL overall, as well as the risk of follicular lymphoma. When vegetables, bean vegetables, cruciferous vegetables, green leafy vegetables, red vegetables, yellow/orange vegetables, fruit, and citrus fruits were examined separately, strong interaction effects were narrowed to vegetable intake among patients with diffuse large B-cell lymphoma. Our results suggest that genetic polymorphisms in oxidative stress pathway genes, especially in the NOS genes, modify the association between vegetable and fruit intake and risk of NHL. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1429–38)
Obesity, Weight Gain, and Risk of Chronic Myeloid Leukemia
Authors: Strom Sara S. , Yamamura Yuko , Kantarijian Hagop M. , Cortes-Franco Jorge E.
Published: May 2009

To date, little is known about the risk factors for the development of chronic myeloid leukemia (CML). Obesity, measured as body mass index, has been identified as a possible risk factor for several solid tumors as well as some adult hematopoietic malignancies. This case-control study (N = 253 cases and 270 controls), conducted at the University of Texas M. D. Anderson Cancer Center, investigated the role of obesity and adulthood weight gain in CML risk. Cases and controls were similar with respect to smoking, alcohol consumption, and occupational solvent and ionizing radiation exposure. Cases were significantly more likely to have a history of occupational exposure to agricultural chemicals (11% cases versus 3% controls, P = 0.001). Cases were more likely to be obese during adulthood compared with controls at age 25 [odds ratios (OR) = 4.29; 95% confidence intervals (95% CI), 1.63-11.3], at age 40 (OR = 5.12; 95% CI, 1.92-13.6), and at diagnosis (OR = 3.09; 95% CI, 1.56-6.13). Obesity at all ages was found to be an independent risk factor, with a significant dose-response effect. Among participants ≥45 years, cases gained significantly more weight each year between ages 25 and 40 compared with controls (0.78 versus 0.44 kg/y, P < 0.001) with the association strongest among those who gained >1 kg/y between 25 and 40 years of age (OR, 3.63; 95% CI, 1.46-9.04). Our results suggest that obesity and adulthood weight gain play important roles in CML risk. Several plausible biological mechanisms have been proposed and warrant further investigation. In the future, cancer prevention interventions aimed at reducing the incidence of CML could be developed. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1501–6)