bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Evaluation of Multiplexed Cytokine and Inflammation Marker Measurements: a Methodologic Study
Authors: Chaturvedi Anil K. , Kemp Troy J. , Pfeiffer Ruth M. , Biancotto Angelique , Williams Marcus , Munuo Stella , Purdue Mark P. , Hsing Ann W. , Pinto Ligia , McCoy J. Philip , Hildesheim Allan
Published: March 2023

Abstract
Background: Chronic inflammation is etiologically related to several cancers. We evaluated the performance [ability to detect concentrations above the assay's lower limit of detection, coefficients of variation (CV), and intraclass correlation coefficients (ICC)] of 116 inflammation, immune, and metabolic markers across two Luminex bead–based commercial kits and three specimen types.

Methods: From 100 cancer-free participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Trial, serum, heparin plasma, and EDTA plasma samples were utilized. We measured levels of 67 and 97 markers using Bio-Rad and Millipore kits, respectively. Reproducibility was assessed using 40 blinded duplicates (20 within-batches and 20 across-batches) for each specimen type.

Results: A majority of markers were detectable in more than 25% of individuals on all specimen types/kits. Of the 67 Bio-Rad markers, 51, 52, and 47 markers in serum, heparin plasma, and EDTA plasma, respectively, had across-batch CVs of less than 20%. Likewise, of 97 Millipore markers, 75, 69, and 78 markers in serum, heparin plasma, and EDTA plasma, respectively, had across-batch CVs of less than 20%. When results were combined across specimen types, 45 Bio-Rad and 71 Millipore markers had acceptable performance (>25% detectability on all three specimen types and across-batch CVs <20% on at least two of three specimen types). Median concentrations and ICCs differed to a small extent across specimen types and to a large extent between Bio-Rad and Millipore.

Conclusions: Inflammation and immune markers can be measured reliably in serum and plasma samples using multiplexed Luminex-based methods.

Impact: Multiplexed assays can be utilized for epidemiologic investigations into the role of inflammation in cancer etiology. Cancer Epidemiol Biomarkers Prev; 20(9); 1902–11. ©2011 AACR.
Data from Lung Cancer Incidence Trends by Histology Type among Asian American, Native Hawaiian, and Pacific Islander Populations in the United States, 1990–2010
Authors: Cheng Iona , Le Gem M. , Noone Anne-Michelle , Gali Kathleen , Patel Manali , Haile Robert W. , Wakelee Heather A. , Gomez Scarlett L.
Published: March 2023

Abstract
Background: Lung cancer is one of the leading cancer sites diagnosed among Asian Americans, Pacific Islanders, and Native Hawaiians (AANHPI). To better understand the patterns of lung cancer incidence among AANHPIs, we examined the incidence trends of five histologic cell types of lung cancer across ten AANHPI populations in comparison with non-Hispanic Whites.

Methods: Lung cancer incidence data from 1990 through 2010 were obtained from 13 U.S. population-based cancer registries. Age-adjusted histologic cell-type–specific incidence rates and 95% confidence intervals were calculated. Joinpoint regression models and annual percentage change (APC) statistics were used to characterize the magnitude and direction of trends.

Results: From 1990 through 2010, incidence rates of adenocarcinoma increased significantly for Filipino and Korean women with a 2.6% and 3.0% annual percentage increase, respectively. More recently, a significant rise in the incidence of adenocarcinoma was observed for Chinese men (1996–2010; APC = 1.3%). Squamous cell carcinoma (SCC) increased 2.4% per year among Japanese women. For SCC, small cell lung carcinoma, large cell and other specified carcinoma, and unspecified types, stable or decreasing trends were observed in most AANHPI groups and non-Hispanic Whites.

Conclusions: AANHPIs demonstrate a range in the burden of lung cancer across histologies and specific populations.

Impact: These findings illustrate the importance of disaggregating AANHPIs into their specific populations. The rise in incidence of adenocarcinoma and SCC among certain AANHPIs demonstrates the need for research into non-tobacco associated risk factors for these populations and targeted efforts for tobacco prevention.

See all the articles in this CEBP Focus section, “Cancer in Asian and Pacific Islander Populations.”

Cancer Epidemiol Biomarkers Prev; 23(11); 2250–65. ©2014 AACR.
Data from Improved Stool DNA Integrity Method for Early Colorectal Cancer Diagnosis
Authors: Rengucci Claudia , De Maio Giulia , Menghi Maura , Scarpi Emanuela , Guglielmo Simona , Fusaroli Pietro , Caletti Giancarlo , Saragoni Luca , Gardini Andrea Casadei , Zoli Wainer , Falcini Fabio , Amadori Dino , Calistri Daniele
Published: March 2023

Abstract
Background: DNA integrity analysis could represent an alternative approach to the early detection of colorectal cancer. Previously, fluorescence long DNA (FL-DNA) in stools was extracted using a manual approach and analyzed by capillary electrophoresis assay (CE FL-DNA). We aimed to improve diagnostic accuracy using a simpler and more standardized method [Real Time PCR FL-DNA (RT FL-DNA)] for the detection of early malignant lesions in a population undergoing colorectal cancer screening.

Methods: From 241 stool samples, DNA was extracted using manual and semiautomatic extraction systems and analyzed using FL-DNA tests by CE and RT assays. The RT FL-DNA approach showed slightly higher sensitivity and specificity compared with the CE FL-DNA method. Furthermore, we compared the RT FL-DNA approach with the iFOBT report.

Results: Nonparametric ranking statistics were used to analyze the relationship between the median values of RT FL-DNA and the clinicohistopathologic characteristics. The median values of both variables were significantly higher in patients with cancer than in patients with noncancerous lesions. According to the Fagan nomogram results, the iFOBT and FL-DNA methods provided more accurate diagnostic information and were able to identify subgroups at varying risks of cancer.

Conclusions: The combination of the semiautomatic extraction system and RT FL-DNA analysis improved the quality of DNA extracted from stool samples.

Impact: RT FL-DNA shows great potential for colorectal cancer diagnosis as it is a reliable and relatively easy analysis to perform on routinely processed stool samples in combination with iFOBT. Cancer Epidemiol Biomarkers Prev; 23(11); 2553–60. ©2014 AACR.
Data from Downregulation of microRNAs 145-3p and 145-5p Is a Long-term Predictor of Postmenopausal Breast Cancer Risk: The ORDET Prospective Study
Authors: Muti Paola , Sacconi Andrea , Hossain Ahmed , Donzelli Sara , Ben Moshe Noa Bossel , Ganci Federica , Sieri Sabina , Krogh Vittorio , Berrino Franco , Biagioni Francesca , Strano Sabrina , Beyene Joseph , Yarden Yosef , Blandino Giovanni
Published: March 2023

Abstract
Background: miRNAs have been implicated in the regulation of key metabolic, inflammatory, and malignant pathways; hence, they might be considered both predictors and players of cancer development.

Methods: Using a case–control study design nested in the ORDET prospective cohort study, we addressed the possibility that specific mRNAs can serve as early predictors of breast cancer incidence in postmenopausal women. We compared leukocyte miRNA profiles of 133 incident postmenopausal breast cancer cases and profiles of 133 women who remained healthy over a follow-up period of 20 years.

Results: The analysis identified 20 differentially expressed miRNAs, 15 of which were downregulated. Of the 20 miRNAs, miR145-5p and miR145-3p, each derived from another arm of the respective pre-miRNA, were consistently and significantly downregulated in all the databases that we surveyed. For example, analysis of more than 1,500 patients (the UK Metabric cohort) indicated that high abundance of miR145-3p and miR145-5p was associated with longer, and for miR145-3p also statistically significant, survival. The experimental data attributed different roles to the identified miRNAs: Although the 5p isoform was associated with invasion and metastasis, the other isoform seems related to cell proliferation.

Conclusions: These observations and the prospective design of our study lend support to the hypothesis that downregulation of specific miRNAs constitutes an early event in cancer development. This finding might be used for breast cancer prevention.

Impact: The identification of the miRNAs as long-term biomarkers of breast cancer may have an impact on breast cancer prevention and early detection. Cancer Epidemiol Biomarkers Prev; 23(11); 2471–81. ©2014 AACR.
Data from Validity and Reliability of the Munsell Soil Color Charts for Assessing Human Skin Color
Authors: Reeder Anthony I. , Iosua Ella , Gray Andrew R. , Hammond Vanessa A.
Published: March 2023

Abstract
Background: Skin pigmentation is a key factor for ultraviolet radiation exposure–related cancers and can make a significant contribution to the patterns of other diseases. For surveys, and to appropriately target cancer control activities, valid and reliable measures of skin color are required.

Methods: Validity and reliability of the Munsell Soil Color Charts were investigated for skin color assessment. The unexposed skin color of 280 university students was measured by spectrophotometer to calculate an Individual Typology Angle (ITA) value, and categorized by two independent raters according to the Munsell system (the latter was repeated after a 7-day interval).

Results: Interrater and intrarater reliability for the Munsell charts was found to be acceptable [intraclass correlation coefficients (ICC) of 0.85 and 0.86, respectively]. When ITA values were converted to the six Del Bino skin color categories, weighted κ for agreement between raters, within rater, and between Munsell chip and spectrophotometer were 0.63, 0.60, and 0.61, respectively. A tendency toward overestimation of the extremes of skin pigmentation was evident, particularly for the “brown” and “dark” skin types.

Conclusions: Study findings suggest that the Munsell Soil Color Charts represent a reliable and valid measurement strategy when assessing skin type.

Impact: The Munsell Year 2000 Soil Color Charts may provide a useful instrument for fieldwork contexts. Subsequent classification of individuals into skin cancer risk categories, rather than the use of precise ITA values, may be sufficient for targeting public health messages for skin cancer prevention and other health risks. Cancer Epidemiol Biomarkers Prev; 23(10); 2041–7. ©2014 AACR.
Data from Can UV Exposure Reduce Mortality?
Authors: Berwick Marianne
Published: March 2023

Abstract
A Swedish cohort analysis in this issue (1) demonstrates a significant reduction in all cause mortality and in cardiovascular mortality associated with several measures of sun exposure. In addition, ultraviolet exposure from tanning beds is associated with a significant increase in all cause mortality and cancer mortality. A potential explanation for the protective association is that UV exposure results in high levels of serum vitamin D which may improve survival. However, that explanation does not hold for ultraviolet exposure from tanning beds, which in this study is associated with a significant increase in all cause mortality and cancer mortality. Such a finding is curious and inconsistent with a vitamin D hypothesis. These results should impel investigators to study further the biology of ultraviolet radiation, both natural and artificial, and its health effects. Cancer Epidemiol Biomarkers Prev; 20(4); 582–4. ©2011 AACR.
Data from Is Human Papillomavirus Viral Load a Clinically Useful Predictive Marker? A Longitudinal Study
Authors: Constandinou-Williams Christothea , Collins Stuart I. , Roberts Sally , Young Lawrence S. , Woodman Ciaran B.J. , Murray Paul G.
Published: March 2023

Abstract
Background: It has been suggested that in women who test positive for high-risk human papillomavirus (HPV) types, viral load can distinguish women who are at increased risk of cervical neoplasia from those who are not.

Methods: Quantitative PCR (qPCR) was used to measure HPV copy number in serial samples taken from 60 and 58 young women previously found to have incident cervical HPV16 or HPV18 infections, respectively, using GP5+/GP6+ primers; women provided at least three samples for qPCR testing, at least one of which was positive.

Results: A 10-fold increase in HPV16 or HPV18 copy number was associated with a modestly increased risk of acquiring a cytologic abnormality [HPV16: hazards ratio, 1.76 (95% confidence interval, 1.38-2.25); HPV18: hazards ratio, 1.59 (95% confidence interval, 1.25-2.03)]. However, in most women, copy number increased during follow-up, before decreasing again. In women with a HPV16 infection, the median copy number per 1,000 cells was 7.7 in their first qPCR HPV-positive sample, 1,237 in the sample yielding the maximum copy number, and 7.8 in their last qPCR HPV-positive sample; corresponding copy numbers for women with HPV18 infection were 2.3, 87, and 2.4. Maximum HPV16 and HPV18 copy number did not differ significantly between women who acquired an incident cervical cytologic abnormality and those who did not.

Conclusion: Whereas large relative increases in copy number are associated with an increased risk of abnormality, a single measurement of viral load made at an indeterminate point during the natural history of HPV infection does not reliably predict the risk of acquiring cervical neoplasia. Therefore, a single measure of HPV viral load cannot be considered a clinically useful biomarker. Cancer Epidemiol Biomarkers Prev; 19(3); 832–7
Data from Patient and Provider Characteristics Associated with Colorectal, Breast, and Cervical Cancer Screening among Asian Americans
Authors: Thompson Caroline A. , Gomez Scarlett Lin , Chan Albert , Chan John K. , McClellan Sean R. , Chung Sukyung , Olson Cliff , Nimbal Vani , Palaniappan Latha P.
Published: March 2023

Abstract
Background: Routinely recommended screening for breast, cervical, and colorectal cancers can significantly reduce mortality from these types of cancer, yet screening is underutilized among Asians. Surveys rely on self-report and often are underpowered for analysis by Asian ethnicities. Electronic health records (EHR) include validated (as opposed to recall-based) rates of cancer screening. In this article, we seek to better understand cancer screening patterns in a population of insured Asian Americans.

Methods: We calculated rates of compliance with cervical, breast, and colorectal cancer screening among Asians from an EHR population and compared them with non-Hispanic whites. We performed multivariable modeling to evaluate potential predictors (at the provider- and patient-level) of screening completion among Asian patients.

Results: Aggregation of Asian subgroups masked heterogeneity in screening rates. Asian Indians and native Hawaiians and Pacific Islanders had the lowest rates of screening in our sample, well below that of non-Hispanic whites. In multivariable analyses, screening completion was negatively associated with patient–physician language discordance for mammography [OR, 0.81; 95% confidence interval (CI), 0.71–0.92] and colorectal cancer screening (OR, 0.79; CI, 0.72–0.87) and positively associated with patient–provider gender concordance for mammography (OR, 1.16; CI, 1.00–1.34) and cervical cancer screening (OR, 1.66; CI, 1.51–1.82). In addition, patient enrollment in online health services increased mammography (OR, 1.32; CI, 1.20–1.46) and cervical cancer screening (OR, 1.31; CI, 1.24–1.37).

Conclusions: Language- and gender-concordant primary care providers and culturally tailored online health resources may help improve preventive cancer screening in Asian patient populations.

Impact: This study demonstrates how the use of EHR data can inform investigations of primary prevention practices within the healthcare delivery setting.

See all the articles in this CEBP Focus section, “Cancer in Asian and Pacific Islander Populations.”

Cancer Epidemiol Biomarkers Prev; 23(11); 2208–17. ©2014 AACR.
Data from Association between Lifestyle Factors and CpG Island Methylation in a Cancer-Free Population
Authors: Brait Mariana , Ford Jean G. , Papaiahgari Srinivas , Garza Mary A. , Lee Jin I. , Loyo Myriam , Maldonado Leonel , Begum Shahnaz , McCaffrey Lee , Howerton Mollie , Sidransky David , Emerson Mark R. , Ahmed Saifuddin , Williams Carla D. , Hoque Mohammad Obaidul
Published: March 2023

Abstract
Background: Many risk factors have been associated with cancer, such as age, family history, race, smoking, high-fat diet, and poor nutrition. It is important to reveal the molecular changes related to risk factors that could facilitate early detection, prevention, and overall control of cancer.

Methods: We selected six cancer-specific methylated genes that have previously been reported in primary tumors and have also been detected in different bodily fluids of cancer patients. Here, we used quantitative fluorogenic real-time methylation-specific PCR in plasma DNA samples for the detection of methylation changes from an asymptomatic population who do not have any known cancer.

Results: The promoter methylation frequencies of the studied genes were as follows: APC (7%), CCND2 (22%), GSTP1 (2%), MGMT (9%), RARβ2 (29%), and P16 (3%). Promoter methylation of at least one of the genes analyzed was observed in ∼46% (72 of 157) of the samples by binary dichotomization. Promoter hypermethylation of at least two genes was detected in 17% (26 of 157) of the samples. RARβ2 methylation was observed in 45% of subjects who had a high-fat diet in contrast with those who had a low-fat diet (23%; P = 0.007).

Discussion: Our findings may help to elucidate early methylation changes that may lead to cancer development. These methylation changes could be due to exposure to risk factors and may be useful for cancer prevention measures such as changes in lifestyle. Longitudinal follow-up of a high-risk population is needed to understand the association of methylation of candidate genes in cancer development. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2984–91)
Data from A Candidate Gene Study of Folate-Associated One Carbon Metabolism Genes and Colorectal Cancer Risk
Authors: Levine A. Joan , Figueiredo Jane C. , Lee Won , Conti David V. , Kennedy Kathleen , Duggan David J. , Poynter Jenny N. , Campbell Peter T. , Newcomb Polly , Martinez Maria Elena , Hopper John L. , Le Marchand Loic , Baron John A. , Limburg Paul J. , Ulrich Cornelia M. , Haile Robert W.
Published: March 2023

Abstract
Background: Folate-associated one-carbon metabolism (FOCM) may play an important role in colorectal carcinogenesis. Variation in FOCM genes may explain some of the underlying risk of colorectal cancer.

Methods: This study utilized data from 1,805 population-based colorectal cancer cases and 2,878 matched sibling controls from the Colon Cancer Family Registry. We used a comprehensive haplotype tagging single nucleotide polymorphism (tagSNP) approach to select 395 tagSNPs in 15 genes involved in folate and vitamin B12 metabolism. Genotyping was done using the Illumina GoldenGate or Sequenom platforms. Risk factor and dietary data were collected using self-completed questionnaires. Microsatellite instability (MSI) status was determined using standard techniques, and tumor subsite was obtained from pathology reports. The association between SNPs and colorectal cancer was assessed using conditional logistic regression with sibships as the matching factor and assuming a log additive or codominant model.

Results: In the log additive model, two linked (r2 = 0.99) tagSNPs in the DHFR gene (rs1677693 and rs1643659) were associated with a significant decrease in colorectal cancer risk after correction for multiple testing (odds ratio, 0.87; 95% confidence interval, 0.71-0.94; P = 0.029; and odds ratio, 0.87; 95% confidence interval, 0.71-0.95; P = 0.034 for rs1677693 and rs1643659, respectively). These two linked (r2 = 0.99) tagSNPs and one tagSNP in the MTR gene (rs4659744) were significantly associated with reduced colorectal cancer risk only among individuals not using multivitamin supplements.

Conclusions: Overall, we found only moderate evidence that genetic variation in 15 folate pathway genes may affect colorectal cancer risk except in non–multivitamin users.

Impact: This study suggests that multivitamin supplement use may modify the association between folate pathway genes and colorectal cancer risk in a post-folic-acid-supplemented population. Cancer Epidemiol Biomarkers Prev; 19(7); 1812–21. ©2010 AACR.
Data from Body Size, Physical Activity, Early-Life Energy Restriction, and Associations with Methylated Insulin-like Growth Factor–Binding Protein Genes in Colorectal Cancer
Authors: Simons Colinda C.J.M. , van den Brandt Piet A. , Stehouwer Coen D.A. , van Engeland Manon , Weijenberg Matty P.
Published: March 2023

Abstract
Background: We investigated body size, physical activity, and early-life energy restriction in relation to colorectal tumors with and without methylated insulin-like growth factor–binding protein (IGFBP) genes, which are putative tumor-suppressor genes.

Methods: We determined IGFBP2, IGFBP3, and IGFBP7 promoter CpG island hypermethylation in tumors of 733 colorectal cancer cases from the Netherlands Cohort Study (N = 120,852). Participants self-reported lifestyle and dietary factors at baseline in 1986. Using a case–cohort approach (N subcohort = 5,000), we estimated hazard ratios (HR) for colorectal cancer by extent of IGFBP methylation.

Results: Comparison of the highest versus lowest sex-specific tertiles of adult body mass index (BMI) gave multivariable-adjusted HRs [95% confidence intervals (CI)] for colorectal cancers with 0 (18.7%), 1 (29.5%), 2 (32.4%), and 3 (19.5%) methylated genes of 1.39 (0.88–2.19), 1.11 (0.77–1.62), 1.67 (1.17–2.38), and 2.07 (1.29–3.33), respectively. Other anthropometric measures and physical activity were not associated with colorectal cancer risk by extent of IGFBP methylation, except height in sex-specific analyses for women. Exposure to energy restriction during the Dutch Hunger Winter versus nonexposure gave HRs (95% CIs) for colorectal cancers with 0, 1, 2, and 3 methylated genes of 1.01 (0.67–1.53), 1.03 (0.74–1.44), 0.72 (0.52–0.99), and 0.50 (0.32–0.78), respectively.

Conclusions: Adult BMI, height (in women only), and early-life energy restriction were associated with the risk of having a colorectal tumor characterized by IGFBP methylation.

Impact: Body size may particularly increase the risk of IGFBP gene–methylated colorectal tumors; this finding might facilitate more targeted approaches to prevent obesity-related colorectal cancers. Cancer Epidemiol Biomarkers Prev; 23(9); 1852–62. ©2014 AACR.
Data from Low Folate Levels Are Associated with Reduced Risk of Colorectal Cancer in a Population with Low Folate Status
Authors: Gylling Björn , Van Guelpen Bethany , Schneede Jörn , Hultdin Johan , Ueland Per Magne , Hallmans Göran , Johansson Ingegerd , Palmqvist Richard
Published: March 2023

Abstract
Background: A diet rich in folate is associated with a reduced colorectal cancer risk, whereas the role of circulating levels is less clear. The aim of this study was to relate prediagnostic plasma folate, vitamin B12, and homocysteine concentrations to the risk of colorectal cancer.

Methods: This was a prospective case–control study of 331 cases and 662 matched controls nested within the population-based Northern Sweden Health and Disease Study. Median follow-up time from recruitment to diagnosis was 10.8 years.

Results: Plasma folate concentrations were positively related to colorectal cancer risk; multivariate odds ratios were 1.62 [95% confidence intervals (CI), 1.08–2.42] and 1.42 (95% CI, 0.94–2.21) for the middle and highest versus lowest tertile, respectively. In subjects with follow-up <10.8 years, a statistically significant doubled risk was observed for the middle and highest versus lowest tertile, whereas findings for longer follow-up times were null. A positive risk relationship was also observed for tumor stage III–IV but not I–II. Plasma vitamin B12 concentrations were inversely associated with rectal cancer risk. Homocysteine was not significantly related to colorectal cancer risk.

Conclusions: In this population-based, nested case–control study, low plasma folate concentrations were associated with a reduced colorectal cancer risk. This protective role was mainly observed in subjects with higher tumor stage or shorter follow-up time between recruitment and diagnosis. Low circulating folate status may protect against colorectal cancer or suppress progression of preneoplastic or neoplastic lesions.

Impact: These findings may have relevance for the ongoing debate about mandatory folic acid fortification of flour. Cancer Epidemiol Biomarkers Prev; 23(10); 2136–44. ©2014 AACR.
Data from The 6q22.33 Locus and Breast Cancer Susceptibility
Authors: Kirchhoff Tomas , Chen Zhang-qun , Gold Bert , Pal Prodipto , Gaudet Mia M. , Kosarin Kristi , Levine Douglas A. , Gregersen Peter , Spencer Sara , Harlan Megan , Robson Mark , Klein Robert J. , Hudis Clifford A. , Norton Larry , Dean Michael , Offit Kenneth
Published: March 2023

Abstract
Recently, we identified a novel breast cancer susceptibility locus at 6q22.33 following a genome-wide association study in the Ashkenazi Jewish genetic isolate. To replicate these findings, we did a case-control association analysis on 6q22.33 (rs2180341) in an additional 487 Ashkenazi Jewish breast cancer cases and in an independent non-Jewish, predominantly European American, population of 1,466 breast cancer cases and 1,467 controls. We confirmed the 6q22.33 association with breast cancer risk in the replication cohorts [per-allele odds ratio (OR), 1.18; 95% confidence interval (95% CI), 1.04-1.33; P = 0.0083], with the strongest effect in the aggregate meta-analysis of 3,039 breast cancer cases and 2,616 Ashkenazi Jewish and non-Jewish controls (per-allele OR, 1.24; 95% CI, 1.13-1.36; P = 3.85 × 10-7). We also showed that the association was slightly stronger with estrogen receptor–positive tumors (per-allele OR, 1.35; 95% CI, 1.20-1.51; P = 2.2 × 10-5) compared with estrogen receptor–negative tumors (per-allele OR, 1.19; 95% CI, 0.97-1.47; P = 0.1). Furthermore, this study provides a novel insight into the functional significance of 6q22.33 in breast cancer susceptibility. Due to the stronger association of 6q22.33 with estrogen receptor–positive breast cancer, we examined the effect of candidate genes on estrogen receptor response elements. Upon transfection of overexpressed RNF146 in the MCF-7 breast cancer cell line, we observed diminished expression of an estrogen receptor response element reporter construct. This study confirms the association of 6q22.33 with breast cancer, with slightly stronger effect in estrogen receptor–positive tumors. Further functional studies of candidate genes are in progress, and a large replication analysis is being completed as part of an international consortium. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2468–75)
Data from Assessing Tumor Mutations to Gain Insight into Base Excision Repair Sequence Polymorphisms and Smoking in Colon Cancer
Authors: Curtin Karen , Samowitz Wade S. , Wolff Roger K. , Ulrich Cornelia M. , Caan Bette J. , Potter John D. , Slattery Martha L.
Published: March 2023

Abstract
DNA repair enzymes function in major pathways to reverse DNA damage, including base excision repair (BER). Missense polymorphisms in BER repair genes may contribute to differences in DNA repair capacity, specific mutations, and susceptibility to cancer in the presence of exposure to carcinogens such as cigarette smoking. In a study of 1,604 incident colon cancer cases and 1,969 matched population-based controls genotyped for BER variants OGG1 (S326C) and XRCC1 (R194W, R280H, and R399Q), we found no associations with colon cancer overall. However, a 2-fold increased risk of BRAF V600E tumor mutation was observed in current and former cigarette smokers homozygous for the OGG1 polymorphism (odds ratio, 2.2; 95% confidence interval, 1.02-4.9, recessive model); similar associations were not observed for microsatellite instability, CpG island methylator phenotype, KRAS2 mutations, or TP53 mutations. The XRCC1 R194W polymorphism was associated with a modest increased risk of TP53 tumor mutations in those who regularly smoked cigarettes (odds ratio, 1.4; 95% confidence interval, 1.02-1.9). These findings point to the importance of studying tumor mutations when examining DNA repair polymorphisms and cigarette smoke exposure to identify potentially relevant associations with colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3384–8)
Data from Systematic Error in Gas Chromatography-Mass Spectrometry–Based Quantification of Hydrolyzed Urinary Steroids
Authors: Moon Ju-Yeon , Ha Young Wan , Moon Myeong Hee , Chung Bong Chul , Choi Man Ho
Published: March 2023

Abstract
Gas chromatography-mass spectrometry–based metabolite profiling can lead to an understanding of various disease mechanisms as well as to identifying new diagnostic biomarkers by comparing the metabolites related in quantification. However, the unexpected transformation of urinary steroids during enzymatic hydrolysis with Helix pomatia could result in an underestimation or overestimation of their concentrations. A comparison of β-glucurondase extracted from Escherichia coli revealed 18 conversions of 84 steroids tested as an unexpected transformation under hydrolysis with β-glucuronidase/arylsulfatase extracted from Helix pomatia. In addition to the conversion of 3β-hydroxy-5-ene steroids into 3-oxo-4-ene steroids, which has been reported, the transformation of 3β-hydroxy-5α–reduced and 3β-hydroxy-5β–reduced steroids to 3-oxo-5α–reduced and 3-oxo-5β–reduced steroids, respectively, was newly observed. The formation of by-products was in proportion to the concentration of substrates becoming saturated against the enzyme. The substances belonging to these three steroid groups were undetectable at low concentrations, whereas the corresponding by-products were overestimated. These results indicate that the systematic error in the quantification of urinary steroids hydrolyzed with Helix pomatia can lead to a misreading of the clinical implications. All these hydrolysis procedures are suitable for study purposes, and the information can help prevent false evaluations of urinary steroids in clinical studies. Cancer Epidemiol Biomarkers Prev; 19(2); 388–97
Data from Circulating Soluble CD30 and Future Risk of Lymphoma; Evidence from Two Prospective Studies in the General Population
Authors: Vermeulen Roel , Hosnijeh Fatemeh Saberi , Portengen Lützen , Krogh Vittorio , Palli Domenico , Panico Salvatore , Tumino Rosario , Sacredote Carlotta , Purdue Mark , Lan Qing , Rothman Nathaniel , Vineis Paolo
Published: March 2023

Abstract
Background: Elevated circulating soluble CD30 (sCD30) has been previously associated with AIDS-related non-Hodgkin lymphoma (NHL) risk. This finding was recently extended to the general population where elevated levels of sCD30 were reported in prediagnostic serum among subjects that developed NHL later in life.

Methods: We carried out a replication study within the Italian European Prospective Investigation into Cancer and Nutrition cohort. Plasma sCD30 concentration was measured by ELISA in prospectively collected blood of 35 B-cell lymphoma cases and 36 matched controls.

Results: We observed significantly increased relative risks for lymphoma with increasing sCD30 levels [OR (95% CI) for second and third tertiles vs. first tertile: 5.5 (1.5–20.2), 4.0 (1.1–13.9), respectively]. In addition, spline analyses showed that the dose–response curve of sCD30 and lymphoma risk was monotonic and quite similar to the risks reported in the previous study.

Conclusion: This replication study adds to the evidence that sCD30 is related to future lymphoma risk in a concentration-dependent manner in the general population.

Impact: The results of this study strengthen the observation that chronic sustained B-cell activation plays an important role in lymphomagenesis. Cancer Epidemiol Biomarkers Prev; 20(9); 1925–7. ©2011 AACR.
Data from Performance of the Genomic Evaluators of Metastatic Prostate Cancer (GEMCaP) Tumor Biomarker for Identifying Recurrent Disease in African American Patients
Authors: Levin Albert M. , Lindquist Karla J. , Avila Andrew , Witte John S. , Paris Pamela L. , Rybicki Benjamin A.
Published: March 2023

Abstract
Evaluation of prostate cancer prognosis after surgery is increasingly relying upon genomic analyses of tumor DNA. We assessed the ability of the biomarker panel Genomic Evaluators of Metastatic Prostate Cancer (GEMCaP) to predict biochemical recurrence in 33 European American and 28 African American prostate cancer cases using genome-wide copy number data from a previous study. “Biomarker positive” was defined as ≥20% of the 38 constituent copy number gain/loss GEMCaP loci affected in a given tumor; based on this threshold, the frequency of a positive biomarker was significantly lower in African Americans (n = 2; 7%) than European Americans (n = 11; 33%; P = 0.013). GEMCaP positivity was associated with risk of recurrence [hazard ratio (HR), 5.92; 95% confidence interval (CI), 2.32–15.11; P = 3 × 10−4] in the full sample and among European Americans (HR, 3.45; 95% CI, 1.13–10.51; P = 0.032) but was not estimable in African Americans due to the low rate of GEMCaP positivity. Overall, the GEMCaP recurrence positive predictive value (PPV) was 85%; in African Americans, PPV was 100%. When we expanded the definition of loss to include copy-neutral loss of heterozygosity (i.e., loss of one allele with concomitant duplication of the other), recurrence PPV was 83% for European American subjects. Under this definition, 5 African American subjects had a positive GEMCaP test value; 4 went on to develop biochemical recurrence (PPV = 80%). Our results suggest that the GEMCaP biomarker set could be an effective predictor for both European American and African American men diagnosed with localized prostate cancer who may benefit from immediate aggressive therapy after radical prostatectomy. Cancer Epidemiol Biomarkers Prev; 23(8); 1677–82. ©2014 AACR.
Data from Risk Prediction Models for Melanoma: A Systematic Review
Authors: Usher-Smith Juliet A. , Emery Jon , Kassianos Angelos P. , Walter Fiona M.
Published: March 2023

Abstract
Melanoma incidence is increasing rapidly worldwide among white-skinned populations. Earlier diagnosis is the principal factor that can improve prognosis. Defining high-risk populations using risk prediction models may help targeted screening and early detection approaches. In this systematic review, we searched Medline, EMBASE, and the Cochrane Library for primary research studies reporting or validating models to predict risk of developing cutaneous melanoma. A total of 4,141 articles were identified from the literature search and six through citation searching. Twenty-five risk models were included. Between them, the models considered 144 possible risk factors, including 18 measures of number of nevi and 26 of sun/UV exposure. Those most frequently included in final risk models were number of nevi, presence of freckles, history of sunburn, hair color, and skin color. Despite the different factors included and different cutoff values for sensitivity and specificity, almost all models yielded sensitivities and specificities that fit along a summary ROC with area under the ROC (AUROC) of 0.755, suggesting that most models had similar discrimination. Only two models have been validated in separate populations and both also showed good discrimination with AUROC values of 0.79 (0.70–0.86) and 0.70 (0.64–0.77). Further research should focus on validating existing models rather than developing new ones. Cancer Epidemiol Biomarkers Prev; 23(8); 1450–63. ©2014 AACR.
Data from Comparison of Exposure to Selected Cigarette Smoke Constituents in Adult Smokers and Nonsmokers in a European, Multicenter, Observational Study
Authors: Lindner Dirk , Smith Stephen , Leroy Claire Martin , Tricker Anthony R.
Published: March 2023

Abstract
Background: This multicenter, observational study was conducted in three European countries (Germany, Switzerland, and the United Kingdom) to determine the exposure of adult cigarette smokers and nonsmokers to selected cigarette smoke constituents: 1,3-butadiene, 2-naphthylamine, 4-aminobiphenyl, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), acrolein, benzene, carbon monoxide, nicotine, pyrene, and o-toluidine.

Methods: Smokers were grouped by tar category (TC) according to the tar yield of their regular cigarette brand: TC1: ≤4 mg tar, TC2: 5–7 mg tar, and TC3: ≥8 mg tar [to the legal tar yield ceiling in the respective countries (10 or 12 mg tar)]. Levels of biomarkers of exposure to the aforementioned cigarette smoke constituents were compared between smokers and nonsmokers, and within smokers across tar categories.

Results: The full population consisted of 1,631 subjects (1,223 smokers and 408 nonsmokers). Biomarkers of exposure were analyzed for 1,558 subjects (valid case population) as follows: 1,159 smokers (TC1: n = 402, TC2: n = 379, TC3: n = 378), and 399 nonsmokers. Exposure levels were higher in smokers than nonsmokers and increased with increasing tar yield and cigarette consumption. An association of tar category and exposure level was observed for all smoke constituents, except pyrene, 4-aminobiphenyl, and o-toluidine, whereas only NNK exposure was different in all three tar categories.

Conclusions: Smoking status and, among smokers, daily cigarette consumption and tar yield were observed to affect biomarker of exposure levels.

Impact: This research provides a comprehensive evaluation of smoke constituent exposure of adult cigarette smokers and nonsmokers in three European countries. Cancer Epidemiol Biomarkers Prev; 20(7); 1524–36. ©2011 AACR.
Data from Attribution of 12 High-Risk Human Papillomavirus Genotypes to Infection and Cervical Disease
Authors: Joura Elmar A. , Ault Kevin A. , Bosch F. Xavier , Brown Darron , Cuzick Jack , Ferris Daron , Garland Suzanne M. , Giuliano Anna R. , Hernandez-Avila Mauricio , Huh Warner , Iversen Ole-Erik , Kjaer Susanne K. , Luna Joaquin , Miller Dianne , Monsonego Joseph , Munoz Nubia , Myers Evan , Paavonen Jorma , Pitisuttithum Punnee , Steben Marc , Wheeler Cosette M. , Perez Gonzalo , Saah Alfred , Luxembourg Alain , Sings Heather L. , Velicer Christine
Published: March 2023

Abstract
Background: We estimated the prevalence and incidence of 14 human papillomavirus (HPV) types (6/11/16/18/31/33/35/39/45/51/52/56/58/59) in cervicovaginal swabs, and the attribution of these HPV types in cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS), using predefined algorithms that adjusted for multiple-type infected lesions.

Methods: A total of 10,656 women ages 15 to 26 years and 1,858 women ages 24 to 45 years were enrolled in the placebo arms of one of three clinical trials of a quadrivalent HPV vaccine. We estimated the cumulative incidence of persistent infection and the proportion of CIN/AIS attributable to individual carcinogenic HPV genotypes, as well as the proportion of CIN/AIS lesions potentially preventable by a prophylactic 9-valent HPV6/11/16/18/31/33/45/52/58 vaccine.

Results: The cumulative incidence of persistent infection with ≥1 of the seven high-risk types included in the 9-valent vaccine was 29%, 12%, and 6% for women ages 15 to 26, 24 to 34, and 35 to 45 years, respectively. A total of 2,507 lesions were diagnosed as CIN or AIS by an expert pathology panel. After adjusting for multiple-type infected lesions, among women ages 15 to 45 years, these seven high-risk types were attributed to 43% to 55% of CIN1, 70% to 78% of CIN2, 85% to 91% of CIN3, and 95% to 100% of AIS lesions, respectively. The other tested types (HPV35/39/51/56/59) were attributed to 23% to 30% of CIN1, 7% to 14% of CIN2, 3% to 4% of CIN3, and 0% of AIS lesions, respectively.

Conclusions: Approximately 85% or more of CIN3/AIS, >70% CIN2, and approximately 50% of CIN1 lesions worldwide are attributed to HPV6/11/16/18/31/33/45/52/58.

Impact: If 9-valent HPV vaccination programs are effectively implemented, the majority of CIN2 and CIN3 lesions worldwide could be prevented, in addition to approximately one-half of CIN1. Cancer Epidemiol Biomarkers Prev; 23(10); 1997–2008. ©2014 AACR.
Data from Detection of Bladder Cancer Using Novel DNA Methylation Biomarkers in Urine Sediments
Authors: Chung Woonbok , Bondaruk Jolanta , Jelinek Jaroslav , Lotan Yair , Liang Shoudan , Czerniak Bogdan , Issa Jean-Pierre J.
Published: March 2023

Abstract
Background: Bladder cancer (BCa) remains a lethal malignancy that can be cured if detected early. DNA hypermethylation is a common epigenetic abnormality in cancer that may serve as a marker of disease activity.

Methods: We selected 10 novel candidate genes from the most frequently hypermethylated genes detected by DNA microarray and bisulfite pyrosequencing of bladder cancers and applied them to detect bladder cancer in urine sediments. We analyzed DNA methylation in the candidate genes by quantitative methylation-specific real-time PCR (qMSP) to detect bladder cancer in urine sediments from 128 bladder cancer patients and 110 age-matched control subjects.

Results: Based on a multigene predictive model, we discovered 6 methylation markers (MYO3A, CA10, SOX11, NKX6-2, PENK, and DBC1) as most promising for detecting bladder cancer. A panel of 4 genes (MYO3A, CA10, NKX6-2, and DBC1 or SOX11) had 81% sensitivity and 97% specificity, whereas a panel of 5 genes (MYO3A, CA10, NKX6-2, DBC1, and SOX11 or PENK) had 85% sensitivity and 95% specificity for detection of bladder cancer (area under curve = 0.939). By analyzing the data by cancer invasiveness, detection rate was 47 of 58 (81%) in non-muscle invasive tumors (pTa, Tis, and pT1) and 62 of 70 (90%) in muscle invasive tumors (T2, T3, and T4).

Conclusions: This biomarker panel analyzed by qMSP may help the early detection of bladder tumors in urine sediments with high accuracy.

Impact: The panel of biomarker deserves validation in a large well-controlled prospectively collected sample set. Cancer Epidemiol Biomarkers Prev; 20(7); 1483–91. ©2011 AACR.
Data from Genome-Based Prediction of Breast Cancer Risk in the General Population: A Modeling Study Based on Meta-Analyses of Genetic Associations
Authors: van Zitteren Moniek , van der Net Jeroen B. , Kundu Suman , Freedman Andrew N. , van Duijn Cornelia M. , Janssens A. Cecile J.W.
Published: March 2023

Abstract
Background: Genome-wide association studies identified novel breast cancer susceptibility variants that could be used to predict breast cancer in asymptomatic women. This review and modeling study aimed to investigate the current and potential predictive performance of genetic risk models.

Methods: Genotypes and disease status were simulated for a population of 10,000 women. Genetic risk models were constructed from polymorphisms from meta-analysis including, in separate scenarios, all polymorphisms or statistically significant polymorphisms only. We additionally investigated the magnitude of the odds ratios (OR) for 1 to 100 hypothetical polymorphisms that would be needed to achieve similar discriminative accuracy as available prediction models [modeled range of area under the receiver operating characteristic curve (AUC) 0.70–0.80].

Results: Of the 96 polymorphisms that had been investigated in meta-analyses, 41 showed significant associations. AUC was 0.68 for the genetic risk model based on all 96 polymorphisms and 0.67 for the 41 significant polymorphisms. Addition of 50 additional variants, each with risk allele frequencies of 0.30, requires per-allele ORs of 1.2 to increase this AUC to 0.70, 1.3 to increase AUC to 0.75, and 1.5 to increase AUC to 0.80. To achieve AUC of 0.80, even 100 additional variants would need per-allele ORs of 1.3 to 1.7, depending on risk allele frequencies.

Conclusion: The predictive ability of genetic risk models in breast cancer has the potential to become comparable to that of current breast cancer risk models.

Impact: Risk prediction based on low susceptibility variants becomes a realistic tool in prevention of nonfamilial breast cancer. Cancer Epidemiol Biomarkers Prev; 20(1); 9–22. ©2011 AACR.
Data from B-Cell Stimulatory Cytokines and Markers of Immune Activation Are Elevated Several Years Prior to the Diagnosis of Systemic AIDS–Associated Non-Hodgkin B-Cell Lymphoma
Authors: Breen Elizabeth Crabb , Hussain Shehnaz K. , Magpantay Larry , Jacobson Lisa P. , Detels Roger , Rabkin Charles S. , Kaslow Richard A. , Variakojis Daina , Bream Jay H. , Rinaldo Charles R. , Ambinder Richard F. , Martinez-Maza Otoniel
Published: March 2023

Abstract
Background: The risk of developing non-Hodgkin lymphoma (NHL) is greatly increased in HIV infection. The aim of this study was to determine whether elevated serum levels of molecules associated with B-cell activation precede the diagnosis of AIDS-associated NHL (AIDS-NHL).

Methods: Serum levels of B-cell activation–associated molecules, interleukin (IL)6, IL10, soluble CD23 (sCD23), sCD27, sCD30, C-reactive protein (CRP), and immunoglobulin E were determined in 179 NHL cases and HIV+ controls in the Multicenter AIDS Cohort Study, collected at up to 3 time points per subject, 0 to 5 years prior to AIDS-NHL diagnosis.

Results: Serum IL6, IL10, CRP, sCD23, sCD27, and sCD30 levels were all significantly elevated in the AIDS-NHL group, when compared with HIV+ controls or with AIDS controls, after adjusting for CD4 T-cell number. Elevated serum levels of B-cell activation–associated molecules were seen to be associated with the development of systemic [non-CNS (central nervous system)] NHL, but not with the development of primary CNS lymphoma.

Conclusions: Levels of certain B-cell stimulatory cytokines and molecules associated with immune activation are elevated for several years preceding the diagnosis of systemic AIDS-NHL. This observation is consistent with the hypothesis that chronic B-cell activation contributes to the development of these hematologic malignancies.

Impact: Marked differences in serum levels of several molecules are seen for several years prediagnosis in those who eventually develop AIDS-NHL. Some of these molecules may serve as candidate biomarkers and provide valuable information to better define the etiology of NHL. Cancer Epidemiol Biomarkers Prev; 20(7); 1303–14. ©2011 AACR.
Data from Polymorphic Variants in Hereditary Pancreatic Cancer Genes Are Not Associated with Pancreatic Cancer Risk
Authors: McWilliams Robert R. , Bamlet William R. , de Andrade Mariza , Rider David N. , Couch Fergus J. , Cunningham Julie M. , Matsumoto Martha E. , Rabe Kari G. , Hammer Traci J. , Petersen Gloria M.
Published: March 2023

Abstract
Background: Inherited risk of pancreatic cancer has been associated with mutations in several genes, including BRCA2, CDKN2A (p16), PRSS1, and PALB2. We hypothesized that common variants in these genes, single nucleotide polymorphisms (SNP), may also influence risk for pancreatic cancer development.

Methods: A clinic-based case-control study in non-Hispanic white persons compared 1,143 patients with pancreatic adenocarcinoma with 1,097 healthy controls. Twenty-eight genes directly and indirectly involved in the Fanconi/BRCA pathway (includes BRCA1, BRCA2, and PALB2) were identified and 248 tag SNPs were selected. In addition, 11 SNPs in CDKN2A, PRSS1, and PRSS2 were selected. Association studies were done at the gene level by principal components analysis, whereas recursive partitioning analysis was used to investigate pathway effects. At the individual SNP level, adjusted additive, dominant, and recessive models were investigated, and gene-environment interactions were also assessed.

Results: Gene level analyses showed no significant association of any genes with altered pancreatic cancer risk. Multiple single SNP analyses showed associations, which will require replication. Exploratory pathway analyses by recursive partitioning showed no association between SNPs and risk for pancreatic cancer.

Conclusion: In a candidate gene and pathway SNP association study analysis, common variations in the Fanconi/BRCA pathway and other candidate familial pancreatic cancer genes are not associated with risk for pancreatic cancer. Cancer Epidemiol Biomarkers Prev 2009;18(9):2549–52)