bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specimen Allocation in Longitudinal Biomarker Studies: Controlling Subject-Specific Effects by Design
Authors: Tworoger Shelley S. , Yasui Yutaka , Chang Lilly , Stanczyk Frank Z. , McTiernan Anne 
Published: June 2022

AbstractIt is important to understand specimen allocation factors that may impact the validity and reliability of results in longitudinal studies examining within-person changes in biomarker levels. Using data from a randomized clinical trial of an exercise intervention in 136 postmenopausal women, we determined the effect of assaying the baseline and follow-up samples of some subjects in different batches on the intervention effect estimates for serum concentrations of estrone, estradiol, testosterone, androstenedione, and dehydroepiandrosterone. Twenty-five subjects had their baseline and 3-month follow-up samples and 50 subjects had their baseline and 12-month samples assayed in different batches; all other subjects had their baseline, 3-month, and 12-month samples assayed in the same batch. Subjects with split samples were reassayed with all samples in the same batch. We compared the estimated regression coefficient for the intervention effect using the split sample data with one estimated excluding the split sample data and one estimated replacing the split sample data with the reassayed data. The median percentage difference in the intervention effect estimate was 59.6% between using versus excluding the split sample data and 74.6% between using the split sample versus using the reassayed data. In general, the coefficients from the model including the split sample data were closer to zero and statistically less significant than those from the models excluding the split sample data or using the reassayed data. These results suggest that bias can be artificially introduced into intervention effect estimates of longitudinal studies if samples from a subject are not assayed in the same batch.
Improved Method for Determination of 1-Hydroxypyrene in Human Urine
Authors: Carmella Steven G. , Le Ky-Anh , Hecht Stephen S. 
Published: June 2022

Abstract
We have developed an improved method for the analysis of human urine for 1-hydroxypyrene (1-HOP), an accepted biomarker of polycyclic aromatic hydrocarbon uptake. This method takes advantage of commercially available 96-well format devices, which expedite sample preparation before quantitation by HPLC with fluorescence detection. In addition to improved speed of analysis, which is critical for the application of this assay in molecular epidemiology studies, the method described here uses an internal standard, 1-hydroxybenz[a]anthracene, improved sample preparation methods, and optimized HPLC and fluorescence detection conditions. The resulting method for analysis of 1-HOP is sensitive (detection limit, 0.05 pmol/mL urine), accurate (as determined by known addition of 1-HOP to urine), and precise [relative SD (RSD), 4.13%]. A longitudinal study of 1-HOP levels in the urine of 10 nonsmokers showed considerable day-to-day (mean RSD, 55.1 %) and week-to-week (mean RSD, 38.2 %) intra-individual variation, indicating the necessity for multiple sampling in studies concerned with relatively small differences in polycyclic aromatic hydrocarbon exposure.
Carbohydrates and the Risk of Breast Cancer among Mexican Women
Authors: Romieu Isabelle , Lazcano-Ponce Eduardo , Sanchez-Zamorano Luisa Maria , Willett Walter , Hernandez-Avila Mauricio 
Published: June 2022

Abstract
Objective: High carbohydrate intake has been hypothesized to be a risk factor for breast cancer, possibly mediated by elevated levels of free insulin, estrogens, and insulin-like growth factor-1. Therefore, we conducted a population-based case-control study among a Mexican population characterized by relatively low fat and high carbohydrate intakes. Methods: Women ages 20 to 75 years, identified through six hospitals in Mexico City (n = 475), were interviewed to obtain data relating to diet (using a food frequency questionnaire) and breast cancer risk factors. Controls (n = 1,391) were selected from the Mexico City population using a national sampling frame. Results: Carbohydrate intake was positively associated with breast cancer risk. Compared with women in the lowest quartile of total carbohydrate intake, the relative risk of breast cancer for women in the highest quartile was 2.22 [95% confidence interval (95% CI) 1.63-3.04], adjusting for total energy and potential confounding variables (P for trend &lt; 0.0001). This association was present in premenopausal and postmenopausal women (for highest versus lowest quartile, odds ratio 2.31, 95% CI 1.36-3.91 in premenopausal women and odds ratio 2.22, 95% CI 1.49-3.30 in postmenopausal women). Among carbohydrate components, the strongest associations were observed for sucrose and fructose. No association was observed with total fat intake. Discussion: In this population, a high percentage of calories from carbohydrate, but not from fat, was associated with increased breast cancer risk. This relation deserves to be investigated further, particularly in populations highly susceptible to insulin resistance.
Relationship between Methylenetetrahydrofolate Reductase C677T and A1298C Genotypes and Haplotypes and Prostate Cancer Risk and Aggressiveness
Authors: Cicek Mine S. , Nock Nora L. , Li Li , Conti David V. , Casey Graham , Witte John S. 
Published: June 2022

Abstract
Previous reports indicate that polymorphisms in the MTHFR gene play a role in cancer development, but their potential impact on prostate cancer has not been well studied. Here, we evaluate the association between two MTHFR polymorphisms, C677T and A1298C, and prostate cancer risk and aggressiveness in a moderately large family-based case-control study (439 cases and 479 sibling controls). Among all study subjects, we observed no association between the C677T variant and prostate cancer but a slight positive association between the A1298C variant and risk of this disease [odds ratio (OR) 1.41, 95% confidence interval (CI) 0.96-2.06; P = 0.08]. When stratifying the study population by disease aggressiveness at diagnosis, the C677T variant was positively associated with risk among men with less advanced disease (OR 1.86, 95% CI 1.00-3.46; P = 0.05). In contrast, when looking at men with more advanced disease, the C677T variant was inversely associated with risk (OR 0.51, 95% CI 0.32-0.82; P = 0.01), whereas the A1298C variant was positively associated with risk (OR 1.79, 95% CI 1.06-3.02; P = 0.03). Furthermore, the 677T-1298A haplotype was positively associated with prostate cancer among men with less advanced disease (OR 1.84, 95% CI 1.07-3.16; P = 0.03) and inversely associated with risk of more advanced disease (OR 0.47, 95% CI 0.29-0.76; P = 0.002). Our findings suggest that 677T and 1298A, or another variant on their haplotype, may be associated with a reduced risk of progression to more advanced prostate cancer.
Validation of p16INK4a as a Marker of Oncogenic Human Papillomavirus Infection in Cervical Biopsies from a Population-Based Cohort in Costa Rica
Authors: Wang Sophia S. , Trunk Marcus , Schiffman Mark , Herrero Rolando , Sherman Mark E. , Burk Robert D. , Hildesheim Allan , Bratti M. Concepcion , Wright Tom , Rodriguez Ana Cecilia , Chen Sabrina , Reichert Anja , von Knebel Doeberitz Christina , Ridder Ruediger , von Knebel Doeberitz Magnus 
Published: June 2022

Abstract
Due to the high prevalence of cancer-associated types of human papillomavirus (HPV) and the poorly reproducible histologic classification of low-grade lesions, identifying infected women at highest risk for cancer prior to neoplastic progression remains a challenge. We therefore explored the utility of p16INK4a immunostaining as a potential diagnostic and prognostic biomarker for cervical neoplasia using paraffin-embedded tissue blocks (punch biopsies and loop electrosurgical excision procedures) obtained from women referred to colposcopy during the enrollment phase of the Guanacaste Project (1993 to 1994). All blocks from 292 women selected by HPV status (HPV negative, nononcogenic HPV positive, or oncogenic HPV positive) and representing the diagnostic spectrum of the population [normal to precancer: cervical intraepithelial neoplasia (CIN) 3] were immunostained for p16INK4a using the p16INK4a research kit based on the monoclonal antibody clone E6H4 (MTM Laboratories, Heidelberg, Germany). For CIN3, the sensitivity of diffuse p16INK4a immunostaining was 100% and the specificity was 95%. For CIN2, the sensitivity and specificity for diffuse staining were 81.1% and 95.4%, respectively. Generalized to the 10,000-woman cohort, this translated to positive predictive value and negative predictive value of 13.9% and 100% for CIN3, respectively, and 20.4% and 99.7% for CIN2 or CIN3, respectively. Of women with an initial diagnosis of less than CIN2 for whom follow-up data for up to 5 to 7 years were available, 44% with diffuse staining developed persistent infection (CIN2 or CIN3). Whereas our data support the diagnostic potential for p16INK4a, further prospective studies with detailed follow-up determining the prognostic capacity of this marker are needed.
Dietary Glycemic Load, Carbohydrate, Sugar, and Colorectal Cancer Risk in Men and Women
Authors: Michaud Dominique S. , Fuchs Charles S. , Liu Simin , Willett Walter C. , Colditz Graham A. , Giovannucci Edward 
Published: June 2022

Abstract
Hyperinsulinemia may explain excess colorectal cancer among individuals who are overweight or inactive. Recent studies have observed elevated colorectal cancer risk among individuals with elevated insulin levels 2 hours after oral glucose challenge or with elevated plasma C-peptide levels. The effect of consuming a high glycemic diet on colorectal risk, however, remains uncertain. Two prospective cohort studies, the Nurses' Health Study and the Health Professionals Follow-up Study, contributed up to 20 years of follow-up. After exclusions, 1,809 incident colorectal cancers were available for analyses. Dietary glycemic load (GL) was calculated as a function of glycemic index (postprandial blood glucose response as compared with a reference food), carbohydrate content, and frequency of intake of individual foods reported on food frequency questionnaires. Multivariable Cox proportional hazards models were used to adjust for potential confounders. Intakes of dietary carbohydrate, GL, overall glycemic index, sucrose, and fructose were not associated with colorectal cancer risk in women. A small increase in risk was observed in men with high dietary GL (multivariate relative risk, 1.32; 95% confidence interval, 0.98-1.79; highest versus lowest quintile), sucrose or fructose (multivariate relative risk, 1.37; 95% confidence interval, 1.05-1.78; highest versus lowest quintile of fructose, P = 0.008). Associations were slightly stronger among men with elevated body mass index (≥25 kg/m2). Results among women were similar after stratifying by body mass index or physical activity. High intakes of GL, fructose, and sucrose were related to an elevated colorectal cancer risk among men. For women, however, these factors did not seem to increase the risk of colorectal cancer.
Risk of Non-Hodgkin's Lymphoma and Family History of Lymphatic, Hematologic, and Other Cancers
Authors: Chatterjee Nilanjan , Hartge Patricia , Cerhan James R. , Cozen Wendy , Davis Scott , Ishibe Naoko , Colt Joanne , Goldin Lynn , Severson Richard K. 
Published: June 2022

Abstract
Background: An elevated risk of developing non-Hodgkin's lymphoma (NHL) has been associated with a family history of NHL and several other malignancies, but the magnitude of risks and mechanisms are uncertain. Methods: We used self-reported family history data from a recent multicenter U.S.-based case-control studies of NHL to evaluate familial aggregation of NHL with various hematolymphoproliferative and other cancers. Estimates of familial aggregation were obtained as hazard ratios (HR) that compare incidence of different cancers in first-degree relatives of NHL cases with that in the first-degree relatives of NHL controls. Limitations of the study included low participation rates (76% for cases and 52% for controls) and potential differential accuracy of recall. Results: Risk of NHL was elevated in relatives of NHL cases [HR, 2.9; 95% confidence interval (95% CI), 0.95–8.53]; the aggregation seems to be stronger for siblings (HR, 7.6; 95% CI, 0.98–58.8) and for male relatives (HR, 6.2; 95% CI, 0.77–50.0). Risk of Hodgkin's lymphoma seems to be also elevated among relatives of early-onset (&lt;50 years) NHL cases (HR, 3.2; 95% CI, 0.88–11.6). Evaluation of family history of other cancers provided modest evidence for an increased risk of melanoma of the skin (HR, 2.9; 95% CI, 1.08–7.75), pancreatic cancer (HR, 2.1; 95% CI, 0.96–4.43), stomach cancer (HR, 1.8; 95% CI, 0.91–3.63), and prostate cancer (HR, 1.3; 95% CI, 0.87–1.99). Conclusions: These results are consistent with previous findings of familial aggregation of NHL, Hodgkin's lymphoma, and a few other cancers. The pattern of male-specific and sibling-specific familial aggregation of NHL we observed, if confirmed, may shed new light on the possible mechanisms that underlie familial aggregation of the disease.
Dietary Intake of Conjugated Linoleic Acids and Risk of Premenopausal and Postmenopausal Breast Cancer, Western New York Exposures and Breast Cancer Study (WEB Study)
Authors: McCann Susan E. , Ip Clement , Ip Margot M. , McGuire Michelle K. , Muti Paola , Edge Stephen B. , Trevisan Maurizio , Freudenheim Jo L. 
Published: June 2022

Abstract
Specific fatty acids may have differential effects on breast cancer etiology. Animal studies have suggested that conjugated linoleic acids (CLA), a group of fatty acids found predominantly in dairy products and the meat of ruminants, have potent anticarcinogenic properties. We examined breast cancer risk and dietary CLA intake among 1,122 women with primary, incident, histologically confirmed breast cancer and 2,036 controls frequency matched to cases by age, race, and county of residence. Diet was assessed with a self-administered 104-item food frequency questionnaire and other relevant data were collected by detailed in-person interviews. We examined risk with intake of total CLAs and the 9c,11t-18:2 isomer of CLA (9,11 CLA). Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression, adjusting for age, the residual of fat adjusted for energy, and other breast cancer risk factors. No association was observed between intakes of total CLA or 9,11 CLA and overall risk of premenopausal or postmenopausal breast cancer. We observed little association between CLA intakes and risk of estrogen receptor (ER)–negative or ER-positive tumors, although, compared with premenopausal women in the lowest quartile of 9,11 CLA intake, those in the highest quartile had a marginally significant reduction in risk of having an ER-negative tumor (odds ratio, 0.40; 95% confidence interval, 0.16–1.01). Our findings suggest that, although CLA intake was not related to overall breast cancer risk, there may be associations with tumor biology at least among premenopausal women.
Overexpression of m-Calpain in Human Colorectal Adenocarcinomas
Authors: Lakshmikuttyamma Ashakumary , Selvakumar Ponniah , Kanthan Rani , Kanthan Selliah Chandra , Sharma Rajendra K. 
Published: June 2022

Abstract
Background: Calpains represent a well-conserved family of Ca2+-dependent proteolytic enzymes. Recently, the importance of calpain in the metastatic process has received great attention. To investigate whether m-calpain contributes to the pathogenesis of colorectal cancer, we investigated the expression of m-calpain and its inhibitors, calpastatin and high-molecular-weight calmodulin-binding protein (HMWCaMBP), in human colorectal surgical specimens. Methods: Fifty cases of colon carcinoma were evaluated for this study. Of 50 cases evaluated, we presented in this report six cases for m-calpain, calpastatin and HMWCaMBP protein expression by Western blot analyses was done in both normal and invasive tumor components of human samples. In addition, immunohistochemistry analysis was also carried out in all patients. Results: The activity and protein expression of m-calpain was significantly higher in colorectal adenocarcinoma than in normal colonic mucosa. This finding was corroborated by immunohistochemical studies that showed strong cytoplasmic staining in the colon tumors with m-calpain antibody. The decreased expression of these calpain inhibitors (calpastatin and HMWCaMBP) paralleled increased activity and expression of calpain in colorectal adenocarcinoma and the well-documented involvement of this Ca2+-dependent protease in colon tumor. Conclusion: Increased activity and moderate staining of m-calpain in polyps show the usage of this enzyme as a marker for the early detection of colorectal adenocarcinoma using immunologic approaches. These findings represent the first description of calpain overexpression in colorectal cancer. This has implications with regard to the design of chemotherapeutic drugs as well as in monitoring colorectal cancer in early stages of the metastatic process.
Ursodiol Use Is Possibly Associated with Lower Incidence of Hepatocellular Carcinoma in Hepatitis C Virus–Associated Liver Cirrhosis
Authors: Tarao Kazuo , Fujiyama Shigetoshi , Ohkawa Shinichi , Miyakawa Kaoru , Tamai Setsuo , Hirokawa Satoru , Masaki Takahiro , Tanaka Katsuaki 
Published: June 2022

Abstract
In a previous study of patients with hepatitis C virus (HCV)–associated liver cirrhosis (HCV-LC), we showed that increased liver inflammation, as assessed by higher serum alanine aminotransferase (ALT), was associated with increased risk for the development of hepatocellular carcinoma (HCC). This suggested that suppression of inflammation might inhibit HCC development in HCV-LC. Several agents have been suggested to possess chemopreventive potential against the development of HCC in chronic HCV-associated liver disease, including herbal medicines, such as Stronger-Neo-Minophagen C (glycyrrhizin) and Sho-saiko-to (TJ-9). Ursodiol [ursodeoxycholic acid (UDCA)], a bile acid widely used to treat cholestatic liver diseases, also possesses anti-inflammatory properties in liver disease. We hypothesized that suppression of liver inflammation, as assessed by decreases in serum ALT, might inhibit HCC occurrence in patients with HCV-LC. In this study, the preventive effect of UDCA on HCC was examined in patients with early-stage HCV-LC. One hundred two patients with HCV-LC (Child stage A) were treated with anti-inflammatory drugs, Stronger-Neo-Minophagen C,Sho-saiko-to, or UDCA, with the goal of lowering the average serum ALT level to &lt;80 IU. Iftheaverage ALT level did not remain &lt;80 IU after treatment with one agent, multiagent therapy was initiated. The patients were followed up for &gt;5 years and were retrospectively subdivided into two groups: 56 UDCA users (group A) and 46 UDCA nonusers (group B). The mean ± SD dosage of UDCA administered in group A was 473.7 ± 183.0 mg/d. The average duration of UDCA administration in group A was 37.3 ± 15.9 months over the 5-year study period. The cumulative incidence of HCC was recorded. The 5-year incidence of HCC in group A was 17.9% (10 of 56) and was significantly lower than that in group B (39.1%, 18 of 46; P = 0.025). The risk for HCC incidence, calculated by a logistic regression model, showed that the administration of UDCA significantly decreased hepatocarcinogenesis (P = 0.036). The herbal medicines used were comparable in dosage and treatment duration in the UDCA and non-UDCA groups. In conclusion, UDCA might prevent HCC development in HCV-LC. Interestingly, because the serum ALT trends over time were nearly the same in both groups, the chemopreventive effectiveness of UDCA was not accompanied by greater reductions in ALT compared with the UDCA nonusers.
Temporal Variation and Identification of Factors Associated with Endogenous Retinoic Acid Isomers in Serum from Brazilian Women
Authors: Siegel Erin M. , Craft Neal E. , Roe Denise J. , Duarte-Franco Eliane , Villa Luisa L. , Franco Eduardo L. , Giuliano Anna R. 
Published: June 2022

AbstractObjective: Retinoids (natural and synthetic derivatives of vitamin A) have cancer chemotherapeutic and chemopreventive activities. Retinoic acid (RA) treatment has been associated with significant regression of preneoplastic lesions. However, serious toxicity associated with some therapies has made long-term chemoprevention in healthy populations unfeasible. Recently, serum RA has been shown to increase in response to oral retinol (vitamin A) supplementation. Here, we assess the variability of circulating RA levels and the lifestyle, demographic, and nutritional factors that explain such variability.Method: Total RA concentration and the concentrations of RA isomers (all-trans-RA, 13-cis-RA, and 9-cis-RA) were measured by high-pressure liquid chromatography in serum samples obtained 4 months apart from 502 women participating in the Ludwig-McGill Cohort (São Paulo, Brazil).Results: The relative abundance of the three RA isomers was similar for each visit (baseline and month 4), with 13-cis-RA having the highest concentrations followed by 9-cis-RA and all-trans-RA. The within-person variability of total RA and individual isomers was low. Using multivariate logistic regression models (upper tertile versus low/middle tertile of serum RA), we found that age, race, oral contraceptive use, total number of pregnancies, and season of initial blood draw were significantly associated with at least one endogenous RA isomer level. All endogenous RA isomers were positively associated with serum retinol, β-carotene, and β-cryptoxanthin levels.Conclusion: These results have implications for the design of future epidemiologic studies focused on assessing RA-disease association and intervention studies aimed at modulating RA levels.
p53 Codon 72 Polymorphic Variants, Loss of Allele-Specific Transcription, and Human Papilloma Virus 16 and/or 18 E6 Messenger RNA Expression in Squamous Cell Carcinomas of the Head and Neck
Authors: Scheckenbach Kathrin , Lieven Oliver , Götte Karl , Bockmühl Ulrike , Zotz Rainer , Bier Henning , Balz Vera 
Published: June 2022

Abstract
A polymorphism at codon 72 of the human tumor suppressor p53 determines translation into either arginine or proline. Yet, the impact of this amino acid variability on the risk to develop malignant tumors, particularly carcinomas associated with human papilloma virus (HPV) infections, remains unresolved because of contradictory results. To address a potential correlation between the different genotypes and the manifestation of squamous cell carcinomas of the head and neck (SCCHN), we determined the p53 codon 72 in 193 healthy subjects and 122 unselected SCCHN with known HPV status. Furthermore, loss of allele-specific transcription was analyzed in p53 codon 72 heterozygous (Arg/Pro) SCCHN and correlated with HPV 16 and/or 18 E6 transcript expression. We found a moderately increased risk (odds ratio, 1.86; 95% confidence interval, 1.0-3.3) for individuals with germ line heterozygosity to develop SCC of the pharynx. On the other hand, p53 codon 72 polymorphic variants, most notably the Arg/Arg genotype, showed no association with the presence of HPV 16 and/or 18 E6 transcript. Moreover, there was no evidence for HPV-driven selection in SCCHN with allele-specific loss of transcription. Our data suggest that the p53 codon 72 polymorphism has a minor impact on the development of SCCHN.