bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Determinants of VIA (Visual Inspection of the Cervix After Acetic Acid Application) Positivity in Cervical Cancer Screening of Women in a Peri-Urban Area in Andhra Pradesh, India
Authors: Vedantham Haripriya , Silver Michelle I. , Kalpana B. , Rekha C. , Karuna B.P. , Vidyadhari K. , Mrudula S. , Ronnett Brigitte M. , Vijayaraghavan K. , Ramakrishna Gayatri , Sowjanya Pavani , Laxmi Shantha , Shah Keerti V. , Gravitt Patti E.
Published: March 2023

Abstract
Objectives: Visual inspection of the cervix after acetic acid application (VIA) is widely recommended as the method of choice in cervical cancer screening programs in resource-limited settings because of its simplicity and ability to link with immediate treatment. In testing the effectiveness of VIA, human papillomavirus DNA testing, and Pap cytology in a population-based study in a peri-urban area in Andhra Pradesh, India, we found the sensitivity of VIA for detection of cervical intraepithelial neoplasia grade 2 and worse (CIN2+) to be 26.3%, much lower than the 60% to 90% reported in the literature. We therefore investigated the determinants of VIA positivity in our study population.

Methods: We evaluated VIA positivity by demographics and reproductive history, results of clinical examination, and results from the other screening methods.

Results: Of the 19 women diagnosed with CIN2+, only 5 were positive by VIA (positive predictive value, 3.1%). In multivariate analysis, VIA positivity (12.74%) was associated with older age, positive Pap smear, visually apparent cervical inflammation, and interobserver variation. Cervical inflammation of unknown cause was present in 21.62% of women. In disease-negative women, cervical inflammation was associated with an increase in VIA positivity from 6.1% to 15.5% (P < 0.001). Among the six gynecologists who performed VIA, the positivity rate varied from 4% to 31%.

Conclusions: The interpretation of VIA is subjective and its performance cannot be readily evaluated against objective standards.

Impact: VIA is not a robust screening test and we caution against its use as the primary screening test in resource-limited regions. Cancer Epidemiol Biomarkers Prev; 19(5); 1373–80. ©2010 AACR.
Data from Cancer Survivorship Research: A Review of the Literature and Summary of Current NCI-Designated Cancer Center Projects
Authors: Harrop J. Phil , Dean Julie A. , Paskett Electra D.
Published: March 2023

Abstract
The number of cancer survivors and the amount of cancer survivorship research have grown substantially during the past three decades. This article provides a review of interventional and observational cancer survivorship research efforts as well as a summary of current cancer survivorship research projects being conducted by National Cancer Institute–designated cancer centers in an effort to identify areas that need further attention. Cancer Epidemiol Biomarkers Prev; 20(10); 2042–7. ©2011 AACR.
Data from Collagen XXIII: A Potential Biomarker for the Detection of Primary and Recurrent Non–Small Cell Lung Cancer
Authors: Spivey Kristin A. , Banyard Jacqueline , Solis Luisa M. , Wistuba Ignacio I. , Barletta Justine A. , Gandhi Leena , Feldman Henry A. , Rodig Scott J. , Chirieac Lucian R. , Zetter Bruce R.
Published: March 2023

Abstract
Background: Collagen XXIII is a transmembrane collagen previously shown to be upregulated in metastatic prostate cancer. The purpose of this study was to determine the protein expression of collagen XXIII in tumor tissues from a variety of cancers and to assess the utility of collagen XXIII as a biomarker for non–small cell lung cancer (NSCLC).

Methods: A multicancer tissue microarray was used for the immunohistochemical examination of collagen XXIII protein expression in a variety of cancers. Subsequently, collagen XXIII expression was analyzed in three separate cohorts using tissue microarrays with representative tumor and control lung tissues from NSCLC patients. In addition, NSCLC patient urine samples were analyzed for the presence of collagen XXIII through Western blot.

Results: Collagen XXIII was present in tissue samples from a variety of cancers. Within lung cancer tissues, collagen XXIII staining was enriched in NSCLC subtypes. Collagen XXIII was present in 294 of 333 (88%) lung adenocarcinomas and 97 of 133 (73%) squamous cell carcinomas. In urine, collagen XXIII was present in 23 of 29 (79%) NSCLC patient samples but only in 15 of 54 (28%) control samples. High collagen XXIII staining intensity correlated with shorter recurrence-free survival in NSCLC patients.

Conclusions: We show the capability of collagen XXIII as a tissue and urinary biomarker for NSCLC, in which positivity in tissue or urine significantly correlates with the presence of NSCLC and high staining intensity is a significant recurrence predictor.

Impact: Inclusion of collagen XXIII in a tissue- or urine-based cancer biomarker panel could inform NSCLC patient treatment decisions. Cancer Epidemiol Biomarkers Prev; 19(5); 1362–72. ©2010 AACR.
Data from Cigarette Smoking and Pulmonary Function in Adult Survivors of Childhood Cancer Exposed to Pulmonary-Toxic Therapy: Results from the St. Jude Lifetime Cohort Study
Authors: Oancea S. Cristina , Gurney James G. , Ness Kirsten K. , Ojha Rohit P. , Tyc Vida L. , Klosky James L. , Srivastava DeoKumar , Stokes Dennis C. , Robison Leslie L. , Hudson Melissa M. , Green Daniel M.
Published: March 2023

Abstract
Treatments for childhood cancer can impair pulmonary function. We assessed the potential impact of cigarette smoking on pulmonary function in 433 adult childhood cancer survivors (CCS) who received pulmonary-toxic therapy, using single breath diffusion capacity for carbon monoxide corrected for hemoglobin (DLCOcorr), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and total lung capacity (TLC). FEV1/FVC median values among current [1.00; interquartile range (IQR): 0.94–1.04] and former smokers (0.98; IQR: 0.93–1.04) were lower than those who had never smoked (1.02; IQR: 0.96–1.06; P = 0.003). Median FEV1/FVC values were lower among those who smoked ≥ 6 pack-years (0.99; IQR: 0.92–1.03) and those who smoked <6 pack-years (1.00; IQR: 0.94–1.04), than among those who had never smoked (P = 0.005). Our findings suggest that CCSs have an increased risk for future obstructive and restrictive lung disease. Follow-up is needed to determine whether smoking imparts more than additive risk. Smoking prevention and cessation need to be a priority in this population. Cancer Epidemiol Biomarkers Prev; 23(9); 1938–43. ©2014 AACR.
Data from 1,3-Butadiene Exposure and Metabolism among Japanese American, Native Hawaiian, and White Smokers
Authors: Park Sungshim Lani , Kotapati Srikanth , Wilkens Lynne R. , Tiirikainen Maarit , Murphy Sharon E. , Tretyakova Natalia , Le Marchand Loïc
Published: March 2023

Abstract
Background: We hypothesize that the differences in lung cancer risk in Native Hawaiians, whites, and Japanese Americans may, in part, be due to variation in the metabolism of 1,3-butadiene, one of the most abundant carcinogens in cigarette smoke.

Methods: We measured two biomarkers of 1,3-butadiene exposure, monohydroxybutyl mercapturic acid (MHBMA) and dihydroxybutyl mercapturic acid (DHBMA), in overnight urine samples among 584 Native Hawaiians, Japanese Americans, and white smokers in Hawaii. These values were normalized to creatinine levels. Ethnic-specific geometric means were compared adjusting for age at urine collection, sex, body mass index, and nicotine equivalents (a marker of total nicotine uptake).

Results: We found that mean urinary MHBMA differed by race/ethnicity (P = 0.0002). The values were highest in whites and lowest in Japanese Americans. This difference was only observed in individuals with the GSTT1-null genotype (P = 0.0001). No difference across race/ethnicity was found among those with at least one copy of the GSTT1 gene (P ≥ 0.72). Mean urinary DHBMA did not differ across racial/ethnic groups.

Conclusions: The difference in urinary MHBMA excretion levels from cigarette smoking across three ethnic groups is, in part, explained by the GSTT1 genotype. Mean urinary MHBMA levels are higher in whites among GSTT1-null smokers.

Impact: The overall higher excretion levels of MHBMA in whites and lower levels of MHBMA in Japanese Americans are consistent with the higher lung cancer risk in the former. However, the excretion levels of MHBMA in Native Hawaiians are not consistent with their disease risk and thus unlikely to explain their high risk of lung cancer.

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

Cancer Epidemiol Biomarkers Prev; 23(11); 2240–9. ©2014 AACR.
Data from Systems Strategies to Support Cancer Screening in U.S. Primary Care Practice
Authors: Yabroff K. Robin , Zapka Jane , Klabunde Carrie N. , Yuan Gigi , Buckman Dennis W. , Haggstrom David , Clauser Steven B. , Miller Jacqueline , Taplin Stephen H.
Published: March 2023

Abstract
Background: Although systems strategies are effective in improving health care delivery, little is known about their use for cancer screening in U.S. primary care practice.

Methods: We assessed primary care physicians' (N = 2,475) use of systems strategies for breast, cervical, and colorectal cancer (CRC) screening in a national survey conducted in 2007. Systems strategies included patient and physician screening reminders, performance reports of screening rates, electronic medical records, implementation of in-practice guidelines, and use of nurse practitioners/physician assistants. We evaluated use of both patient and physician screening reminders with other strategies in separate models by screening type, adjusted for the effects of physician and practice characteristics with multivariate logistic regression.

Results: Fewer than 10% of physicians used a comprehensive set of systems strategies to support cancer screening; use was greater for mammography and Pap testing than for CRC screening. In adjusted analyses, performance reports of cancer screening rates, medical record type, and in-practice guidelines were associated with use of both patient and physician screening reminders for mammography, Pap testing, and CRC screening (P < 0.05).

Conclusion: Despite evidence supporting use of systems strategies in primary care, few physicians report using a comprehensive set of strategies to support cancer screening.

Impact: Current health policy initiatives underscore the importance of increased implementation of systems strategies in primary care to improve the use and quality of cancer screening in the United States. Cancer Epidemiol Biomarkers Prev; 20(12); 2471–9. ©2011 AACR.
Data from Polymorphisms at the Microseminoprotein-β Locus Associated with Physiologic Variation in β-Microseminoprotein and Prostate-Specific Antigen Levels
Authors: Xu Xing , Valtonen-André Camilla , Sävblom Charlotta , Halldén Christer , Lilja Hans , Klein Robert J.
Published: March 2023

Abstract
Background: rs10993994, a single nucleotide polymorphism (SNP) at the genetic locus encoding β-microseminoprotein (β-MSP), is associated with both prostate cancer risk and levels of blood prostate-specific antigen (PSA), a biomarker used in prostate cancer screening. Therefore, we wished to determine the association between SNPs at MSMB, the gene encoding β-MSP, and the levels of prostate-produced biomarkers β-MSP, PSA, and human kallikrein 2 (hK2) in blood and semen.

Methods: Blood and semen from 304 healthy young Swedish men (ages 18-21) were assayed for β-MSP, PSA, and hK2. SNPs around MSMB were genotyped from matched DNA and analyzed for quantitative association with biomarker levels. Empirical P values were multiple test–corrected and the independence of each SNP's effect was determined.

Results: rs10993994 was significantly associated with the blood and semen levels of β-MSP (both P < 1.0 × 10−7) and PSA (P = 0.00014 and P = 0.0019), and semen levels of hK2 (P = 0.00027). Additional copies of the prostate cancer risk allele resulted in lower β-MSP but higher PSA levels, and singly explained 23% and 5% of the variation seen in semen β-MSP and PSA, respectively. Additional SNPs at MSMB are associated with β-MSP and PSA independently of rs10993994.

Conclusions: SNPs at MSMB correlate with physiologic variation in β-MSP and PSA levels in the blood and semen of healthy young Swedish men. In particular, rs10993994 has a strong effect on β-MSP levels.

Impact: Our results suggest a mechanism by which rs10993994 might predispose to prostate cancer and raise the possibility that genetic variation might need to be considered in interpreting the levels of these biomarkers. Cancer Epidemiol Biomarkers Prev; 19(8); 2035–42. ©2010 AACR.
Data from Vitamin D Related Genes, CYP24A1 and CYP27B1, and Colon Cancer Risk
Authors: Dong Linda M. , Ulrich Cornelia M. , Hsu Li , Duggan David J. , Benitez Debbie S. , White Emily , Slattery Martha L. , Farin Fred M. , Makar Karen W. , Carlson Christopher S. , Caan Bette J. , Potter John D. , Peters Ulrike
Published: March 2023

Abstract
Genetic association studies investigating the role of vitamin D in colon cancer have primarily focused on the vitamin D receptor (VDR), with limited data available for other genes in the vitamin D pathway, including vitamin D activating enzyme 1-α hydroxylase (CYP27B1) and vitamin D deactivating enzyme 24-α hydroxylase (CYP24A1). We evaluated whether 12 tagging single nucleotide polymorphisms (SNP) in CYP24A1, identified by resequencing the gene in 32 Caucasian samples, and 1 SNP in CYP27B1 were associated with colon cancer risk. In addition, we evaluated whether these two genes modify associations between colon cancer on the one hand and total vitamin D intake and UV-weighted sun exposure on the other, as well as other variants in VDR. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the association between polymorphisms and haplotypes in CYP27B1 and CYP24A1 in a multicenter population-based case-control study of 1,600 cases and 1,949 controls. The CYP24A1 polymorphism IVS4-66T > G showed a statistically significant association with risk of colon cancer overall, particularly for proximal colon cancer. When stratified by anatomic site, we also found statistically significant associations for three CYP24A1 polymorphisms with risk of distal colon cancer (IVS4 + 1653C > T: OR for CT/TT versus CC, 0.81; 95% CI, 0.68-0.96; IVS9 + 198T > C: OR for CC versus TT, 1.33; 95% CI, 1.03-1.73; and within whites only: +4125bp 3′ of STPC > G: OR for GG versus CC, 1.44; 95% CI, 1-2.05). In addition, a possible interaction between CYP27B1 and UV-weighted sun exposure with proximal colon cancer was observed. As this is the first study to evaluate these genes in relation to colon cancer, additional studies are needed to confirm these results. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2540–8)
Data from Investigation of the Prevalence and Number of Aberrant Crypt Foci Associated with Human Colorectal Neoplasm
Authors: Sakai Eiji , Takahashi Hirokazu , Kato Shingo , Uchiyama Takashi , Hosono Kunihiro , Endo Hiroki , Maeda Shin , Yoneda Masato , Taguri Masataka , Nakajima Atsushi
Published: March 2023

Abstract
Background: Aberrant crypt foci (ACF) are considered to be useful as surrogate biomarker for colorectal cancer (CRC), but the biological significance of ACF remains controversial. We attempted to investigate the relationship between the presence of ACF and human colorectal carcinogenesis using a relatively large sample size.

Methods: We carried out high-magnification chromoscopic colonoscopy to identify ACFs in 861 subjects undergoing a diagnostic endoscopy at the Yokohama City University Hospital. The present study compared the prevalence and number of ACFs in three subject groups (normal subjects, adenoma cases, and CRC cases). The correlations between the demographic and behavioral characteristics of the subjects and the prevalence of ACFs were also assessed.

Results: The prevalence of ACF was 64%, 88%, and 95%, and the mean number of ACF was 3.6, 6.2, and 10.1, in normal subjects, adenoma cases, and CRC cases, respectively. When differences in the prevalence and number of ACFs among age- and sex-stratified subject groups were examined, significant stepwise increments from normal subjects to adenoma cases to CRC cases were apparent (P < 0.001). Moreover, an age- and sex-adjusted multiple logistic regression analysis revealed that smoking and alcohol habits had a synergistic effect, increasing the prevalence of ACFs as well as the risk of CRC (P < 0.001).

Conclusions: These results suggested that ACF may serve as a reliable surrogate biomarker for human colorectal carcinogenesis.

Impact: The use of ACF as an endpoint may enable the size, duration, and cost of CRC chemoprevention studies to be reduced. Cancer Epidemiol Biomarkers Prev; 20(9); 1918–24. ©2011 AACR.
Data from HPV Seroconversion Following Anal and Penile HPV Infection in HIV-Negative and HIV-Infected MSM
Authors: Mooij Sofie H. , Landén Olivia , van der Klis Fiona R.M. , van der Sande Marianne A.B. , de Melker Hester E. , Xiridou Maria , van Eeden Arne , Heijman Titia , Speksnijder Arjen G.C.L. , Snijders Peter J.F. , Schim van der Loeff Maarten F.
Published: March 2023

Abstract
Background: We assessed human papillomavirus (HPV) seroconversion following anal and penile HPV infection in HIV-negative and HIV-infected men who have sex with men (MSM).

Methods: MSM aged ≥18 years were recruited in Amsterdam, the Netherlands (2010–2011), and followed up semiannually. Antibodies against 7 high-risk HPV types in baseline and 12-month serum samples were tested using a multiplex immunoassay. Baseline, 6-, and 12-month anal and penile samples were tested for HPV DNA using the SPF10-PCR DEIA/LiPA25 system. Statistical analyses were performed using logistic regression with generalized estimating equations.

Results: Of 644 MSM included in the analysis, 245 (38%) were HIV-infected. Median age was 38 years for HIV-negative and 47 years for HIV-infected MSM (P < 0.001). Seroconversion against ≥1 of the 7 HPV types was observed in 74 of 396 (19%) HIV-negative and 52 of 223 (23%) HIV-infected MSM at risk (P = 0.2). Incident [adjusted OR (aOR) 2.0; 95% confidence interval (CI), 1.1–3.4] and persistent (aOR 3.7; 95% CI, 1.5–9.5) anal HPV infections were independently associated with type-specific seroconversion in HIV-negative MSM. In HIV-infected MSM, there was a nonsignificant positive association between penile HPV infection at any time point and seroconversion (aOR 1.7; 95% CI, 0.9–3.2).

Conclusions: Incident or persistent anal HPV infection was an independent determinant of seroconversion in HIV-negative MSM.

Impact: Our data support that seroresponse may vary per anatomic site and that persistent HPV infections are more likely to elicit a detectable humoral immune response. Cancer Epidemiol Biomarkers Prev; 23(11); 2455–61. ©2014 AACR.
Data from Chromosome 3p12.3-p14.2 and 3q26.2-q26.32 Are Genomic Markers for Prognosis of Advanced Nasopharyngeal Carcinoma
Authors: Sheu Jim Jinn-Chyuan , Lee Chia-Huei , Ko Jenq-Yuh , Tsao George S.W. , Wu Chung-Chun , Fang Chih-Yeu , Tsai Fuu-Jen , Hua Chun-Hung , Chen Chi-Long , Chen Jen-Yang
Published: March 2023

Abstract
Purpose: Nasopharyngeal carcinoma is an epithelial malignancy with a remarkable racial and geographic distribution. Previous cytogenetic studies have shown nasopharyngeal carcinoma to be characterized by gross genomic aberrations. However, identification of susceptible gene loci in advanced nasopharyngeal carcinoma has been poorly discussed.

Experimental Design: A genome-wide survey of gene copy number changes was initiated with two nasopharyngeal carcinoma cell lines by array-based comparative genomic hybridization analysis. These alterations were confirmed by a parallel analysis with the data from the gene expression microarray and were validated by quantitative PCR. Clinical association of the defined target genes was analyzed by fluorescence in situ hybridization on 48 metastatic tumors.

Results: A high percentage of genes were consistently altered in dosage and expression levels with gain on 3q26.2-q26.32 and losses on 3p12.3-p14.2 and 9p21.3-p23. Six candidate genes, GPR160 (3q26.2-q27), SKIL (3q26), ADAMTS9 (3p14.2-p14.3), LRIG1 (3p14), MPDZ (9p22-p24), and ADFP (9p22.1) were validated by quantitative PCR. Fluorescence in situ hybridization studies revealed amplification of GPR160 (in 25% of cases) and SKIL (33%); and deletion of ADAMTS9 (30%), LRIG1 (35%), MPDZ (15%), and ADFP (15%). Clinical association analyses indicated a poor survival rate with genetic alterations at the defined 3p deletion (P = 0.0012) and the 3q amplification regions (P = 0.0114).

Conclusion: The combined microarray technologies suggested novel candidate oncogenes, amplification of GPR160 and SKIL at 3q26.2-q26.32, and deletion of tumor suppressor genes ADAMTS9 and LRIG1 at 3p12.3-p14.2. Altered expression of these genes may be responsible for malignant progression and could be used as potential markers for nasopharyngeal carcinoma. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2709–16)
Data from Men with Low Serum Cholesterol Have a Lower Risk of High-Grade Prostate Cancer in the Placebo Arm of the Prostate Cancer Prevention Trial
Authors: Platz Elizabeth A. , Till Cathee , Goodman Phyllis J. , Parnes Howard L. , Figg William D. , Albanes Demetrius , Neuhouser Marian L. , Klein Eric A. , Thompson Ian M. , Kristal Alan R.
Published: March 2023

Abstract
Background: Several prospective studies suggest that use of cholesterol-lowering statin drugs is inversely associated with advanced stage and possibly high-grade prostate cancer. One study reported that men with low cholesterol had a lower risk of high-grade prostate cancer. Given these findings, we investigated the association between low serum cholesterol and prostate cancer risk in the Prostate Cancer Prevention Trial.

Methods: We conducted a cohort study of 5,586 men ages ≥55 years who were randomized to the placebo arm of the Prostate Cancer Prevention Trial between 1993 and 1996. Serum cholesterol was measured enzymatically at entry. By the end of follow-up, 1,251 prostate cancer cases were confirmed. We used logistic regression to calculate the multivariable odds ratio (OR) of total, and Gleason 2 to 6 (n = 993), 7 (n = 199), and 8 to 10 (n = 59) prostate cancer comparing low serum (normal, <200 mg/dL) to high-serum (borderline and elevated cholesterol, ≥200 mg/dL) cholesterol.

Results: Men with low cholesterol had a lower risk of Gleason 8 to 10 prostate cancer [OR, 0.41; 95% confidence interval (CI), 0.22-0.77] than men with high cholesterol. No association was present for prostate cancer overall (OR, 0.97; 95% CI, 0.85-1.11), Gleason 2 to 6 disease (OR, 1.03; 95% CI, 0.89-1.18), or Gleason 7 disease (OR, 0.93; 95% CI, 0.69-1.24).

Conclusion: These prospective results support that men with low cholesterol have a reduced risk of high-grade prostate cancer. These and other contemporary data that suggest that cholesterol metabolism should be investigated further in the etiology of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2807–13)
Data from A Long-term Prospective Study of Type-Specific Human Papillomavirus Infection and Risk of Cervical Neoplasia Among 20,000 Women in the Portland Kaiser Cohort Study
Authors: Schiffman Mark , Glass Andrew G. , Wentzensen Nicolas , Rush Brenda B. , Castle Philip E. , Scott David R. , Buckland Julie , Sherman Mark E. , Rydzak Greg , Kirk Peter , Lorincz Attila T. , Wacholder Sholom , Burk Robert D.
Published: March 2023

Abstract
Background: Human papillomavirus (HPV) DNA testing is more sensitive than cytology for detection of cervical intraepithelial neoplasia grade 3 and cancer (≥CIN3). Adding HPV testing to cytology is recommended for women ≥30 but long-term prospective studies of HPV testing are rare.

Methods: Beginning in 1989–1990, ∼20,000 women in a prepaid health maintenance organization (median age = 34) were followed passively by recommended annual cytology. We tested archived cervicovaginal lavage specimens collected at enrollment, primarily by MY09-MY11 PCR-based methods, for carcinogenic HPV types. We calculated positive and negative predictive values for the entire study period, and Kaplan–Meier estimates of cumulative probability for ≥CIN3, up to 18 years of follow-up.

Results: We observed 15 cases of invasive cervical cancer during the study period, and 189 cases of CIN3. Predictive values and Kaplan–Meier analyses yielded the same conclusions. In women 30 and older, the reassurance against ≥CIN3 following a single negative HPV test was long-lasting (cumulative probability = 0.7% during follow-up). In this age group, a single HPV test (positive vs. negative, hazard ratio of 8.5, 95% CI = 4.8–15.1) provided greater long-term risk stratification than a single cytologic result (abnormal vs. normal, HR = 2.9, 95% CI = 1.2–6.6). The risk for ≥CIN3 was higher for HPV16 than for the average of the other carcinogenic types (hazard ratio = 2.7).

Conclusion and Impact: The data from this cohort study show the long-term predictive value of HPV testing, particularly in women ≥30, and a possible role for distinguishing particularly carcinogenic types like HPV16. Cancer Epidemiol Biomarkers Prev; 20(7); 1398–409. ©2011 AACR.
Data from Changes in CpG Islands Promoter Methylation Patterns during Ductal Breast Carcinoma Progression
Authors: Hoque Mohammad Obaidul , Prencipe Maria , Poeta Maria Luana , Barbano Raffaela , Valori Vanna Maria , Copetti Massimiliano , Gallo Antonietta Pia , Brait Mariana , Maiello Evaristo , Apicella Adolfo , Rossiello Raffaele , Zito Francesco , Stefania Tommasi , Paradiso Angelo , Carella Massimo , Dallapiccola Bruno , Murgo Roberto , Carosi Illuminato , Bisceglia Michele , Fazio Vito Michele , Sidransky David , Parrella Paola
Published: March 2023

Abstract
Aberrant promoter methylation of several known or putative tumor suppressor genes occurs frequently during carcinogenesis, and this epigenetic change has been considered as a potential molecular marker for cancer. We examined the methylation status of nine genes (APC, CDH1, CTNNB1, TIMP3, ESR1, GSTP1, MGMT, THBS1, and TMS1), by quantitative methylation specific PCR. Synchronous preinvasive lesions (atypical ductal hyperplasia and/or ductal carcinoma in situ) and invasive ductal breast carcinoma from 52 patients, together with pure lesions from 24 patients and 12 normal tissues paired to tumor and 20 normal breast distant from tumor were analyzed. Aberrant promoter methylation was detected in both preinvasive and invasive lesions for genes APC, CDH1, CTNNB1, TIMP3, ESR1, and GSTP1. However, hierarchical mixed model and Generalized Estimating Equations model analyses showed that only APC, CDH1, and CTNNB1 promoter regions showed a higher frequency and methylation levels in pathologic samples when compared with normal breast. Whereas APC and CTNNB1 did not show differences in methylation levels or frequencies, CDH1 showed higher methylation levels in invasive tumors as compared with preinvasive lesions (P < 0.04, Mann-Whitney test with permutation correction). The analysis of APC, CDH1, and CTNNB1 methylation status was able to distinguish between normal and pathologic samples with a sensitivity of 67% (95% confidence interval, 60-71%) and a specificity of 75% (95% confidence interval, 69-81%). Our data point to the direct involvement of APC, CDH1, and CTNNB1 promoter methylation in the early stages of breast cancer progression and suggest that they may represent a useful tool for the detection of tumor cells in clinical specimens. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2694–700)
Data from Effect of Long-term Storage in TRIzol on Microarray-Based Gene Expression Profiling
Authors: Ma Wencai , Wang Michael , Wang Zhi-Qiang , Sun Luhong , Graber David , Matthews Jairo , Champlin Richard , Yi Qing , Orlowski Robert Z. , Kwak Larry W. , Weber Donna M. , Thomas Sheeba K. , Shah Jatin , Kornblau Steven , Davis Richard E.
Published: March 2023

Abstract
Background: Although TRIzol is widely used for preservation and isolation of RNA, there is suspicion that prolonged sample storage in TRIzol may affect array-based gene expression profiling (GEP) through premature termination during reverse transcription.

Methods: GEP on Illumina arrays compared paired aliquots (cryopreserved or stored in TRIzol) of primary samples of multiple myeloma (MM) and acute myeloid leukemia (AML). Data were analyzed at the “probe level” (a single consensus value) or “bead level” (multiple measurements provided by individual beads).

Results: TRIzol storage does not affect standard probe-level comparisons between sample groups: different preservation methods did not generate differentially expressed probes (DEP) within MM or AML sample groups, or substantially affect the many DEPs distinguishing between these groups. Differences were found by gene set enrichment analysis, but these were dismissible because of instability with permutation of sample labels, unbalanced restriction to TRIzol aliquots, inconsistency between MM and AML groups, and lack of biological plausibility. Bead-level comparisons found many DEPs within sample pairs, but most (73%) were <2-fold changed. There was no consistent evidence that TRIzol causes premature reverse transcription termination. Instead, a subset of DEPs were systematically due to increased signals in TRIzol-preserved samples from probes near the 5′ end of transcripts, suggesting better mRNA preservation with TRIzol.

Conclusions: TRIzol preserves RNA quality well, without a deleterious effect on GEP. Samples stored frozen with and without TRIzol may be compared by GEP with only minor concern for systematic artifacts.

Impact: The standard practice of prolonged sample storage in TRIzol is suitable for GEP. Cancer Epidemiol Biomarkers Prev; 19(10); 2445–52. ©2010 AACR.
Data from A Systematic Review of p53 as a Prognostic Factor of Survival in Squamous Cell Carcinoma of the Four Main Anatomical Subsites of the Head and Neck
Authors: Tandon Sankalap , Tudur-Smith Catrin , Riley Richard D. , Boyd Mark T. , Jones Terence M.
Published: March 2023

Abstract
Objectives: To summarize existing evidence about whether the presence of mutant or upregulated p53 is a prognostic factor for patients presenting with squamous cell carcinoma arising from the larynx, oropharynx, hypopharynx, or oral cavity.

Method: Relevant articles were identified using strict criteria for systematic searches. Associations between mutant or upregulated p53 versus wild-type or low/undetectable p53 in relation to overall survival and DFS were summarized by extracting or deriving hazard ratio (HR) estimates. Random-effects meta-analyses were used to account for between-study heterogeneity and to summarize the effect of p53 across studies.

Results: The meta-analyses gave a statistically significant pooled HR for overall survival in oral cavity [pooled HR, 1.48; 95% confidence interval, (95% CI), 1.03-2.11], and for disease-free survival in oral cavity (pooled HR, 1.47; 95% CI, 1.12-1.93) and in oropharynx (pooled HR, 0.45; 95% CI, 0.27-0.73). Despite attempts to limit it, between-study heterogeneity was large in the majority of meta-analyses and the prognostic value of p53 was generally inconsistent and inconclusive across studies.

Conclusion: The meta-analysis results highlight that current evidence about the prognostic value of p53 in patients with squamous cell carcinaoma of the head and neck is inconclusive. Large heterogeneity exists across studies in study-level and patient-level characteristics, making it difficult to ascertain a clear picture. Future studies are required in which p53 expression is investigated in a more standardized and biologically informative manner. In particular, prospectively planned individual patient data meta-analyses are needed to establish the prognostic importance of p53 for specific subgroups of patients undergoing specific treatments. Cancer Epidemiol Biomarkers Prev; 19(2); 574–87
Data from Serum Lipid Profile and Risk of Prostate Cancer Recurrence: Results from the SEARCH Database
Authors: Allott Emma H. , Howard Lauren E. , Cooperberg Matthew R. , Kane Christopher J. , Aronson William J. , Terris Martha K. , Amling Christopher L. , Freedland Stephen J.
Published: March 2023

Abstract
Background: Evidence for an association between total cholesterol, low- and high-density lipoproteins (LDL and HDL, respectively), triglycerides, and prostate cancer is conflicting. Given that prostate cancer and dyslipidemia affect large proportions of Western society, understanding these associations has public health importance.

Methods: We conducted a retrospective cohort analysis of 843 radical prostatectomy (RP) patients who never used statins before surgery within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analysis was used to investigate the association between cholesterol, LDL, HDL, and triglycerides and biochemical recurrence risk. In secondary analysis, we explored these associations in patients with dyslipidemia, defined using National Cholesterol Education Program guidelines.

Results: Elevated serum triglycerides were associated with increased risk of prostate cancer recurrence [HRper 10 mg/dl, 1.03; 95% confidence interval (CI), 1.01–1.05] but associations between total cholesterol, LDL and HDL, and recurrence risk were null. However, among men with dyslipidemia, each 10 mg/dl increase in cholesterol and HDL was associated with 9% increased recurrence risk (HR, 1.09; 95% CI, 1.01–1.17) and 39% reduced recurrence risk (HR, 0.61; 95% CI, 0.41–0.91), respectively.

Conclusions: Elevated serum triglycerides were associated with increased risk of prostate cancer recurrence. Cholesterol, LDL, or HDL were not associated with recurrence risk among all men. However, among men with dyslipidemia, elevated cholesterol and HDL levels were associated with increased and decreased risk of recurrence, respectively.

Impact: These findings, coupled with evidence that statin use is associated with reduced recurrence risk, suggest that lipid levels should be explored as a modifiable risk factor for prostate cancer recurrence. Cancer Epidemiol Biomarkers Prev; 23(11); 2349–56. ©2014 AACR.
Data from The Relationship between Umbilical Cord Estrogens and Perinatal Characteristics
Authors: Hickey Martha , Hart Roger , Keelan Jeffrey A.
Published: March 2023

Abstract
Background: Prenatal estrogen exposure is thought to contribute to later life diseases such as breast cancer. However, few studies have directly measured prenatal estrogens and most have relied on proposed “markers” of estrogen exposure. We used a large population-based birth cohort to directly measure the relationship between prenatal estrogens and perinatal characteristics, including putative markers of estrogen exposure.

Methods: Total estrone (E1), estradiol (E2), estriol (E3), and estetrol (E4) were assayed by liquid chromatography/tandem mass spectrometry from archived mixed arterial and venous serum from 860 umbilical cord blood samples.

Results: Values for all estrogens were strongly intercorrelated. Cord estrogen concentrations did not differ between males and females. Levels of all estrogens were reduced in twins and concentrations increased with gestational age. Neither E1 nor E2 was correlated with birth weight, but E3 and E4 levels correlated weakly, whereas onset of labor was associated with higher estrogen concentrations. E1 and E2 concentrations were not associated with preeclampsia in the current pregnancy, but E3 and E4 concentrations were lower in pregnancies complicated by preeclampsia and antepartum hemorrhage.

Conclusions: Umbilical cord estrogen concentrations vary with gestational age, mode of delivery, pregnancy complications, and twinning, but not with infant sex. Putative markers of prenatal estrogen exposure, preeclampsia, and birth weight did not correlate with direct fetal measures of the most potent estrogen (E2) but were associated with weaker estrogens (E3 and E4). Twins had lower concentrations of all estrogens.

Impact: This is the largest and best characterized dataset of prenatal estrogen concentrations, measured using highly accurate mass spectrometry/spectroscopy. These observations represent the new “gold standard” for umbilical cord estrogens, and will inform the interpretation of other datasets and the early life origins of health and disease. Cancer Epidemiol Biomarkers Prev; 23(6); 946–52. ©2014 AACR.
Data from PTGS2 (Cyclooxygenase-2) Expression and Survival among Colorectal Cancer Patients: A Systematic Review
Authors: Kunzmann Andrew T. , Murray Liam J. , Cardwell Chris R. , McShane Charlene M. , McMenamin Úna C. , Cantwell Marie M.
Published: March 2023

Abstract
Background: Studies have examined whether tumor expression of PTGS2 (also known as COX-2), an enzyme inhibited by nonsteroidal anti-inflammatory drugs such as aspirin, is associated with prognosis in patients with colorectal cancer. However, results to date have been mixed.

Methods: Using terms for PTGS2 and colorectal cancer, the Medline, Embase, and Web of Science databases were systematically searched for studies published, in any language, until December 2011. Random effects meta-analyses were used to calculate pooled HRs [95% confidence intervals (CI)] for the association between PTGS2 expression and tumor recurrence, colorectal cancer–specific survival, and overall survival.

Results: In total, 29 studies, which had prognostic data on 5,648 patients, met the inclusion criteria. PTGS2-positive patients were at an increased risk of tumor recurrence (n = 9 studies; HR, 2.79; 95% CI, 1.76–4.41; P < 0.001) and had poorer colorectal cancer–specific survival (n = 7; HR, 1.36; 95% CI, 1.02–1.82; P = 0.04). However, there was funnel plot asymmetry, possibly due to publication bias, for the association with cancer-specific survival but less so for recurrence. PTGS2 expression was not associated with overall survival [(n = 16; pooled unadjusted HR, 1.30; 95% CI, 0.94–1.79; P = 0.11) and (n = 9; pooled adjusted HR, 1.02; 95% CI, 0.72–1.45; P = 0.91)].

Conclusions: PTGS2 expression was associated with an increased risk of tumor recurrence and poorer colorectal cancer–specific survival but not overall survival among patients with colorectal cancer. However, confounding by tumor characteristics such as tumor stage seems likely.

Impact: There is insufficient evidence to recommend PTGS2 expression as a prognostic marker in patients with colorectal cancer. Furthermore, studies providing adjusted results are required. Cancer Epidemiol Biomarkers Prev; 22(9); 1490–7. ©2013 AACR.
Data from Association between Regular Aspirin Use and Circulating Markers of Inflammation: A Study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Lang Kuhs Krystle A. , Hildesheim Allan , Trabert Britton , Kemp Troy J. , Purdue Mark P. , Wentzensen Nicolas , Katki Hormuzd A. , Pinto Ligia A. , Loftfield Erikka , Safaeian Mahboobeh , Chaturvedi Anil K. , Shiels Meredith S.
Published: March 2023

Abstract
Background: Regular aspirin use may decrease cancer risk by reducing chronic inflammation. However, associations between aspirin use and circulating markers of inflammation have not been well studied.

Methods: Serum levels of 78 inflammatory markers were measured in 1,819 55- to 74-year-old men and women in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Data were combined from three completed case–control studies and reweighted to the PLCO screening arm. Self-reported aspirin and ibuprofen use (number of tablets taken per day/week/month) over the previous 12 months was collected at baseline. Associations between (i) nonregular (<4 tablets/month), (ii) low (1–4 tablets/week), (iii) moderate (1 tablet/day), or (iv) high (2+ tablets/day) regular aspirin or ibuprofen use and marker levels were assessed with weighted logistic regression.

Results: Aspirin use was nominally associated with (Ptrend across categories ≤ 0.05) decreased levels of chemokine C-C motif ligand 15 [CCL15; OR, 0.5; 95% confidence intervals (CI), 0.3–0.8; moderate versus nonregular use]; soluble vascular endothelial growth factor receptor 2 (sVEGFR2; OR, 0.7; 95% CI, 0.4–1.0); soluble tumor necrosis factor receptor 1 (sTNFR1; OR, 0.6; 95% CI, 0.4–0.9) and increased levels of CCL13 (OR, 1.3; 95% CI, 0.8–2.1); CCL17 (OR, 1.1; 95% CI, 0.7–1.9) and interleukin 4 (IL4; OR, 1.6; 95% CI, 0.9–2.8). Trends were not statistically significant following correction for multiple comparisons. Likewise, no statistically significant associations were observed between ibuprofen use and marker levels.

Conclusions: No significant associations were observed between regular aspirin use and the inflammatory markers assessed.

Impact: Additional studies are needed to better understand the relationship between aspirin use, chronic inflammation, and cancer risk. Cancer Epidemiol Biomarkers Prev; 24(5); 825–32. ©2015 AACR.
Data from Telomere Length and Breast Cancer Prognosis: A Systematic Review
Authors: Ennour-Idrissi Kaoutar , Maunsell Elizabeth , Diorio Caroline
Published: March 2023

Abstract
Telomeres ensure genome integrity during replication. Loss of telomeric function leads to cell immortalization and accumulation of genetic alterations. The association of telomere length (TL) with breast cancer prognosis is examined through a systematic review. Electronic databases (MEDLINE, EMBASE, CENTRAL), from inception to December 2015, and relevant reviews were searched. Studies that evaluated TL (blood and/or tumor) in association with breast cancer survival or prognostic factor were included. Thirty-six studies met inclusion criteria. Overall risk of bias was critical. Eight studies reported survival outcomes. Overall, there was a trend toward an association of longer telomeres with better outcomes (tumor, not blood). Of the 33 studies reporting associations with prognostic factors, nine adjusted for potential confounders. Among the latter, shorter telomeres were associated with older age (blood, not tumor), higher local recurrence rates (normal tissue), higher tumor grade (tumor), and lower physical activity (blood), which were reported in one study each. TL was not associated with molecular subtype (blood, one study), family history (tumor, one study), chemotherapy (blood, three of four studies), and stress reduction interventions (blood, two of two studies). Although major methodologic differences preclude from drawing conclusive results, TL could be a valuable breast cancer prognostic marker. Cancer Epidemiol Biomarkers Prev; 26(1); 3–10. ©2016 AACR.
Data from Impact of Smoking and Excess Body Weight on Overall and Site-Specific Cancer Mortality Risk
Authors: Meyer Julia , Rohrmann Sabine , Bopp Matthias , Faeh David
Published: March 2023

Abstract
Background: Smoking and excess body weight are major preventable risk factors for premature death. This study aimed at analyzing their single and combined association with site-specific cancer mortality.

Methods: Our study population comprised 35,784 men and women of ages 14 to 99 years, who participated in population-based health surveys conducted 1977–1993 in Switzerland and were followed up for mortality until 2008. Multivariable Cox proportional hazards models were calculated for different cancer sites, and population attributable fractions were derived.

Results: The hazard ratio of dying from cancer (all sites) was 2.32 (95% confidence interval, 2.04–2.63) for heavy smokers (vs. never smokers) and 1.15 (1.01–1.32) for obese [body mass index (BMI) ≥ 30 kg/m2] vs. normal weight individuals. Heavy smoking (≥20 cigarettes/day) was associated with increased mortality due to cancer of the lung, upper aero-digestive tract, pancreas, bladder, liver, and the total of remaining sites. Obesity was associated with higher risk of dying from cancer of the liver and the female genital tract (essentially corpus or cervix uteri and ovary). More than 20% of all cancer deaths in our population were attributable to ever smoking and overweight (BMI ≥ 25 kg/m2).

Conclusions: Smoking was a much stronger risk factor for cancer than excess body weight. For lung, liver, and pancreatic cancer, the combination of excess body weight and smoking lead to cumulated higher risks.

Impact: Our findings support recommendations for obese persons to quit smoking despite potential postcessation weight gain. Cancer Epidemiol Biomarkers Prev; 24(10); 1516–22. ©2015 AACR.
Data from Prospective Population-Based Study of the Association between Serum 25-Hydroxyvitamin-D Levels and the Incidence of Specific Types of Cancer
Authors: Skaaby Tea , Husemoen Lise Lotte Nystrup , Thuesen Betina Heinsbæk , Pisinger Charlotta , Jørgensen Torben , Roswall Nina , Larsen Sofus Christian , Linneberg Allan
Published: March 2023

Abstract
Background: Observational studies have suggested an inverse association between vitamin D status and cancer. We investigated the prospective associations between vitamin D status and the total and specific type of cancer in three cohorts from the general Danish population.

Methods: A total of 12,204 individuals 18 to 71 years old were included. The level of 25-hydroxyvitamin D was measured at baseline, and information about cancer was obtained from the Danish Cancer Registry.

Results: During the 11.3-year median follow-up time, there were 1,248 incident cancers. HRs [95% confidence intervals (CI)] per 10 nmol/L higher baseline vitamin D level were: for all cancers (HR = 1.02; 95% CI, 0.99–1.04), all cancers excluding non-melanoma skin cancer, NMSC (HR = 1.00; 95% CI, 0.97–1.03), head and neck cancer (HR = 0.97; 95% CI, 0.84–1.12), colorectal cancer (HR = 0.95; 95% CI, 0.88–1.02), cancer of bronchus and lung (HR = 0.98; 95% CI, 0.91–1.05), breast cancer (HR = 1.02; 95% CI, 0.96–1.09), cancer of the uterus (HR = 1.10; 95% CI, 0.95–1.27), prostate cancer (HR = 1.00; 95% CI, 0.93–1.08), cancer of the urinary organs (HR = 1.01; 95% CI, 0.90–1.14), NMSC (HR = 1.06; 95% CI, 1.02–1.10), and malignant melanoma (HR = 1.06; 95% CI, 0.95–1.17).

Conclusions: Apart from a significantly higher risk for NMSC with higher vitamin D status, we found no statistically significant associations between vitamin D status and total or specific cancers.

Impact: Our results do not indicate that there is an impact of vitamin D on total cancer incidence. Cancer Epidemiol Biomarkers Prev; 23(7); 1220–9. ©2014 AACR.
Data from A Genome-Wide Association Study of Cutaneous Squamous Cell Carcinoma among European Descendants
Authors: Siiskonen Satu J. , Zhang Mingfeng , Li Wen-Qing , Liang Liming , Kraft Peter , Nijsten Tamar , Han Jiali , Qureshi Abrar A.
Published: March 2023

Abstract
Background: No GWAS on the risk of cutaneous squamous cell carcinoma (SCC) has been published. We conducted a multistage genome-wide association study (GWAS) to identify novel genetic loci for SCC.

Methods: The study included 745 SCC cases and 12,805 controls of European descent in the discovery stage and 531 SCC cases and 551 controls of European ancestry in the replication stage. We selected 64 independent loci that showed the most significant associations with SCC in the discovery stage (linkage disequilibrium r2 < 0.4) for replication.

Results: Rs8063761 in the DEF8 gene on chromosome 16 showed the strongest association with SCC (P = 1.7 × 10−9 in the combined set; P = 1.0 × 10−6 in the discovery set and P = 4.1 × 10−4 in the replication set). The variant allele of rs8063761 (T allele) was associated with a decreased expression of DEF8 (P = 1.2 × 10−6). Besides, we validated four other SNPs associated with SCC in the replication set, including rs9689649 in PARK2 gene (P = 2.7 × 10−6 in combined set; P = 3.2 × 10−5 in the discovery; and P = 0.02 in the replication), rs754626 in the SRC gene (P = 1.1 × 10−6 in combined set; P = 1.4 × 10−5 in the discovery and P = 0.02 in the replication), rs9643297 in ST3GAL1 gene (P = 8.2 × 10−6 in combined set; P = 3.3 × 10−5 in the discovery; and P = 0.04 in the replication), and rs17247181 in ERBB2IP gene (P = 4.2 × 10−6 in combined set; P = 3.1 × 10−5 in the discovery; and P = 0.048 in the replication).

Conclusion: Several genetic variants were associated with risk of SCC in a multistage GWAS of subjects of European ancestry.

Impact: Further studies are warranted to validate our finding and elucidate the genetic function of these variants. Cancer Epidemiol Biomarkers Prev; 25(4); 714–20. ©2016 AACR.