bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Reduced Overall and Event-Free Survival among Colon Cancer Patients Using Dual System Care
Authors: Tarlov Elizabeth , Lee Todd A. , Weichle Thomas W. , Durazo-Arvizu Ramon , Zhang Qiuying , Perrin Ruth , Bentrem David , Hynes Denise M.
Published: March 2023

Abstract
Background: Many veterans have dual Veterans Administration (VA) and Medicare healthcare coverage. We compared 3-year overall and cancer event-free survival (EFS) among patients with nonmetastatic colon cancer who obtained substantial portions of their care in both systems and those whose care was obtained predominantly in the VA or in the Medicare fee-for-service system.

Methods: We conducted a retrospective observational cohort study of patients older than 65 years with stages I to III colon cancer diagnosed from 1999 to 2001 in VA and non-VA facilities. Dual use of VA and non-VA colon cancer care was categorized as predominantly VA use, dual use, or predominantly non-VA use. Extended Cox regression models evaluated associations between survival and dual use.

Results: VA and non-VA users (all stages) had reduced hazard of dying compared with dual users [e.g., for stage I, VA HR 0.40, 95% confidence interval (CI): 0.28–0.56; non-VA HR 0.54, 95% CI: 0.38–0.78). For EFS, stage I findings were similar (VA HR 0.47, 95% CI: 0.35–0.62; non-VA HR 0.64, 95% CI: 0.47–0.86). Stage II and III VA users, but not non-VA users, had improved EFS (stage II: VA HR 0.74, 95% CI: 0.56–0.97; non-VA HR 0.92, 95% CI: 0.69–1.22; stage III: VA HR 0.73, 95% CI: 0.56–0.94; non-VA HR 0.81, 95% CI: 0.62–1.06).

Conclusions: Improved survival among VA and non-VA compared with dual users raises questions about coordination of care and unmet needs.

Impact: Additional study is needed to understand why these differences exist, why patients use both systems, and how systems may be improved to yield better outcomes in this population. Cancer Epidemiol Biomarkers Prev; 21(12); 2231–41. ©2012 AACR.
Data from Adherence to Dietary and Lifestyle Recommendations and Prostate Cancer Risk in the Prostate Testing for Cancer and Treatment (ProtecT) Trial
Authors: Er Vanessa , Lane J. Athene , Martin Richard M. , Emmett Pauline , Gilbert Rebecca , Avery Kerry N.L. , Walsh Eleanor , Donovan Jenny L. , Neal David E. , Hamdy Freddie C. , Jeffreys Mona
Published: March 2023

Abstract
Background: The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) published eight recommendations for cancer prevention, but they are not targeted at prostate cancer prevention. We investigated whether adherence to the WCRF/AICR recommendations and a prostate cancer dietary index is associated with prostate cancer risk.

Methods: We conducted a nested case–control study of 1,806 prostate-specific antigen (PSA)–detected prostate cancer cases and 12,005 controls in the ProtecT trial. We developed a prostate cancer dietary index by incorporating three dietary factors most strongly associated with prostate cancer. Scores were computed to quantify adherence to the WCRF/AICR recommendations and the prostate cancer dietary index separately.

Results: The prostate cancer dietary index score was associated with decreased risk of prostate cancer [OR per 1 score increment: 0.91; 95% confidence interval (CI): 0.84–0.99; Ptrend = 0.04] but the WCRF/AICR index score was not (OR: 0.99; 95% CI: 0.94–1.05; Ptrend = 0.71). There was no heterogeneity in association by prostate cancer stage (P = 0.81) or grade (P = 0.61). Greater adherence to recommendations to increase plant foods (OR per 0.25 index score increment: 0.94; 95% CI: 0.89–0.99; Ptrend = 0.02) and tomato products (OR adherence vs. nonadherence: 0.82; 95% CI: 0.70–0.97; P = 0.02) was inversely associated with overall prostate cancer risk.

Conclusions: Adherence to the prostate cancer–specific dietary recommendations was associated with decreased risk of prostate cancer. High intake of plant foods and tomato products in particular may help protect against prostate cancer.

Impact: Meeting the WCRF/AICR recommendations alone is insufficient for prostate cancer prevention. Additional dietary recommendations should be developed. Cancer Epidemiol Biomarkers Prev; 23(10); 2066–77. ©2014 AACR.
Data from Nicotine Withdrawal Sensitivity, Linkage to chr6q26, and Association of OPRM1 SNPs in the SMOking in FAMilies (SMOFAM) Sample
Authors: Hardin Jill , He Yungang , Javitz Harold S. , Wessel Jennifer , Krasnow Ruth E. , Tildesley Elizabeth , Hops Hyman , Swan Gary E. , Bergen Andrew W.
Published: March 2023

Abstract
Background: Nicotine withdrawal symptoms are related to smoking cessation. A Rasch model has been used to develop a unidimensional sensitivity score representing multiple correlated measures of nicotine withdrawal. A previous autosome-wide screen identified a nonparametric linkage (NPL) log-likelihood ratio (LOD) score of 2.7 on chromosome 6q26 for the sum of nine withdrawal symptoms.

Methods: The objectives of these analyses were to (a) assess the influence of nicotine withdrawal sensitivity on relapse, (b) conduct autosome-wide NPL analysis of nicotine withdrawal sensitivity among 158 pedigrees with 432 individuals with microsatellite genotypes and nicotine withdrawal scores, and (c) explore family-based association of single nucleotide polymorphism (SNP) at the mu opioid receptor candidate gene (OPRM1) with nicotine withdrawal sensitivity in 172 nuclear pedigrees with 419 individuals with both SNP genotypes and nicotine withdrawal scores.

Results: An increased risk for relapse was associated with nicotine withdrawal sensitivity score (odds ratio, 1.25; 95% confidence interval, 1.10-1.42). A maximal NPL LOD score of 3.15, suggestive of significant linkage, was identified at chr6q26 for nicotine withdrawal sensitivity. Evaluation of 18 OPRM1 SNPs via the family-based association test with the nicotine withdrawal sensitivity score identified eight tagging SNPs with global P values <0.05 and false discovery rate Q values <0.06.

Conclusion: An increased risk of relapse, suggestive linkage at chr6q26, and nominally significant association with multiple OPRM1 SNPs were found with Rasch-modeled nicotine withdrawal sensitivity scores in a multiplex smoking pedigree sample. Future studies should attempt to replicate these findings and investigate the relationship between nicotine withdrawal symptoms and variation at OPRM1.(Cancer Epidemiol Biomarkers Prev 2009;18(12):3399–406)
Data from Determinants of Hair Nicotine Concentrations in Nonsmoking Women and Children: A Multicountry Study of Secondhand Smoke Exposure in Homes
Authors: Kim Sungroul , Wipfli Heather , Navas-Acien Ana , Dominici Francesca , Avila-Tang Erika , Onicescu Georgiana , Breysse Patrick , Samet Jonathan M.
Published: March 2023

Abstract
The main purpose of this study was to identify and evaluate determinants of hair nicotine concentrations in nonsmoking women and children exposed to secondhand tobacco smoke at home. Hair samples were collected from nonsmoking women (n = 852) and from children (n = 1,017) <11 years of age living in households (n = 1,095) with smokers from 31 countries from July 2005 to October 2006. Participants' ages, activity patterns and socioeconomic characteristics including education and employment status, and hair treatment information were collected. Multilevel linear regression modeling was used to identify the main determinants of hair nicotine concentration measured by gas chromatography coupled with mass spectrometry. Increased indoor air nicotine concentration at home were associated with increased hair nicotine concentrations in nonsmoking women and children. This association was not changed after controlling for other explanatory variables. After controlling for age, length of exposure, and socioeconomic characteristics, hair nicotine concentrations in nonsmoking children and women were estimated to be increased by 3% and 1%, respectively, for a 1 μg/m3 increase in air nicotine concentration. The association between children's exposure to secondhand tobacco smoke at home and hair nicotine concentration was stronger among younger children and children with longer exposure at home. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3407–14)
Data from A Peripheral Circulating TH1 Cytokine Profile Is Inversely Associated with Prostate Cancer Risk in CLUE II
Authors: Bhavsar Nrupen A. , Bream Jay H. , Meeker Alan K. , Drake Charles G. , Peskoe Sarah B. , Dabitao Djeneba , De Marzo Angelo M. , Isaacs William B. , Platz Elizabeth A.
Published: March 2023

Abstract
Background: TH1 cytokines, such as IFNγ and TNFα, and potentially innate cytokines, such as IL6, can potentiate the immune response to tumor. Cytokines, such as IL1β, IL8, and IL10, may suppress anticancer immunity. Thus, we prospectively evaluated the association between peripheral-cytokine concentrations and prostate cancer.

Methods: We conducted an age-race matched case–control study (268 pairs) of incident prostate cancer in CLUE-II. We measured plasma IFNγ, IL10, IL12p70, IL1β, IL6, IL8, and TNFα concentrations using an ultrasensitive multiplex kit. ORs and 95% confidence intervals (CI) were calculated using conditional logistic regression.

Results: The OR of prostate cancer decreased across quartiles of IFNγ (highest vs. lowest quartiles: OR, 0.49; 95% CI, 0.30–0.81; Ptrend = 0.006), TNFα (OR, 0.56; 95% CI, 0.33–0.96; Ptrend = 0.01), and IL6 (OR, 0.46; 95% CI, 0.26–0.79; Ptrend = 0.007). Higher TNFα (OR, 0.28; 95% CI, 0.09–0.85; Ptrend = 0.01) and IL6 (OR, 0.20; 95% CI, 0.06–0.67; Ptrend = 0.003) concentrations were associated with lower Gleason sum ≥7 disease risk. Other cytokines were not as clearly associated with risk.

Conclusions: Men with a prediagnostic circulating TH1 profile and higher IL6 may have a lower risk of prostate cancer, including aggressive disease. Whether this profile reflects (i) an intraprostatic immune environment in benign tissue that protects against prostate cancer, (ii) the immune milieu in response to a prostate adenocarcinoma that inhibits tumor growth and detectability, and/or (iii) a systemic immune profile that mediates the influence of modifiable factors on risk, warrants additional study.

Impact: Identifying specific inflammatory cytokines associated with prostate cancer may lead to improved prevention and treatment strategies. Cancer Epidemiol Biomarkers Prev; 23(11); 2561–7. ©2014 AACR.
Data from Clinical Trials Methods for Evaluation of Potential Reduced Exposure Products
Authors: Hatsukami Dorothy K. , Hanson Karen , Briggs Anna , Parascandola Mark , Genkinger Jeanine M. , O'Connor Richard , Shields Peter G.
Published: March 2023

Abstract
Potential reduced exposure products (PREPs) to tobacco toxicants may have promise in reducing tobacco-related morbidity or mortality or may promote greater harm to individuals or the population. Critical to determining the risks or benefits from these products are valid human clinical trial PREP assessment methods. Such an assessment involves determining the effects of these products on biomarkers of exposure and effect, which serve as proxies for harm, and assessing the potential for consumer uptake and abuse of the product. This article identifies critical methodologic issues associated with PREP assessments, reviews the methods that have been used to assess PREPs, and describes the strengths and limitations of these methods. Additionally, recommendations are provided for clinical trial PREP assessment methods and future research directions in this area based on this review and on the deliberations from a National Cancer Institute sponsored Clinical Trials PREP Methods Workshop. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3143–95)
Data from Genetic Variation in the Vitamin D Receptor (VDR) and the Vitamin D–Binding Protein (GC) and Risk for Colorectal Cancer: Results from the Colon Cancer Family Registry
Authors: Poynter Jenny N. , Jacobs Elizabeth T. , Figueiredo Jane C. , Lee Won H. , Conti David V. , Campbell Peter T. , Levine A. Joan , Limburg Paul , Le Marchand Loic , Cotterchio Michelle , Newcomb Polly A. , Potter John D. , Jenkins Mark A. , Hopper John L. , Duggan David J. , Baron John A. , Haile Robert W.
Published: March 2023

Abstract
Epidemiologic evidence supports a role for vitamin D in colorectal cancer (CRC) risk. Variants in vitamin D–related genes might modify the association between vitamin D levels and CRC risk. In this analysis, we did a comprehensive evaluation of common variants in the vitamin D receptor (VDR) and the vitamin D–binding protein (GC; group-specific component) genes using a population-based case–unaffected sibling control design that included 1,750 sibships recruited into the Colon Cancer Family Registry. We also evaluated whether any associations differed by calcium supplement use, family history of CRC, or tumor characteristics. Heterogeneity by calcium and vitamin D intake was evaluated for a subset of 585 cases and 837 sibling controls who completed a detailed food frequency questionnaire. Age- and sex-adjusted associations were estimated using conditional logistic regression. Overall, we did not find evidence for an association between any single-nucleotide polymorphism (SNP) in VDR or GC and risk for CRC (range of unadjusted P values 0.01-0.98 for VDR and 0.07-0.95 for GC). None of these associations was significant after adjustment for multiple comparisons. We also found no evidence that calcium or vitamin D intake (food and supplement) from the food frequency questionnaire modified the association estimates between VDR and GC SNPs and CRC. We did observe associations between SNPs in GC and microsatellite unstable CRC, although these results should be confirmed in additional studies. Overall, our results do not provide evidence for a role of common genetic variants in VDR or GC in susceptibility to CRC. Cancer Epidemiol Biomarkers Prev; 19(2); 525–36
Data from Selenium and Bladder Cancer Risk: a Meta-analysis
Authors: Amaral André F.S. , Cantor Kenneth P. , Silverman Debra T. , Malats Núria
Published: March 2023

Abstract
Background: Selenium is considered to be an antioxidant, and its high levels have been inversely associated with cancer risk of several sites. This meta-analysis examined the relationship between levels of selenium measured in serum and toenails, and the risk of bladder cancer.

Methods: A meta-analysis using data from seven published epidemiologic studies (three case-control, three nested case-control, one case-cohort) published before March 2010 was done to examine the association between levels of selenium and bladder cancer. Fixed and random effects analyses were done to calculate meta-odds ratio (mOR) and 95% confidence intervals (CI). Heterogeneity among studies was measured by the I2 statistic.

Results: Overall, the risk of bladder cancer was inversely associated with elevated levels of selenium according to a random-effects model (mOR = 0.61; 95% CI, 0.42-0.87). The mORs were 0.95 (95% CI, 0.69-1.27) and 0.55 (95% CI, 0.32-0.95) among men and women, respectively. Sex, type of sample specimen, smoking status, and study design were found to be potential sources of heterogeneity.

Conclusions: A significant protective effect of selenium, observed mainly among women, may result from gender-specific differences in its accumulation and excretion. The heterogeneity found among studies was mainly linked to the different biological sample specimens used to measure the selenium concentrations and the small size of the studies. Although these results suggest a protective effect of selenium for bladder cancer risk, additional large studies are warranted to support these preliminary evidence.

Impact: The present results suggest a beneficial effect of high selenium intake for bladder cancer risk. Cancer Epidemiol Biomarkers Prev; 19(9); 2407–15. ©2010 AACR.
Data from An Admixture Scan in 1,484 African American Women with Breast Cancer
Authors: Fejerman Laura , Haiman Christopher A. , Reich David , Tandon Arti , Deo Rahul C. , John Esther M. , Ingles Sue A. , Ambrosone Christine B. , Bovbjerg Dana Howard , Jandorf Lina H. , Davis Warren , Ciupak Gregory , Whittemore Alice S. , Press Michael F. , Ursin Giske , Bernstein Leslie , Huntsman Scott , Henderson Brian E. , Ziv Elad , Freedman Matthew L.
Published: March 2023

Abstract
African American women with breast cancer present more commonly with aggressive tumors that do not express the estrogen receptor (ER) and progesterone receptor (PR) compared with European American women. Whether this disparity is the result of inherited factors has not been established. We did an admixture-based genome-wide scan to search for risk alleles for breast cancer that are highly differentiated in frequency between African American and European American women, and may contribute to specific breast cancer phenotypes, such as ER-negative (ER−) disease. African American women with invasive breast cancer (n = 1,484) were pooled from six population-based studies and typed at ∼1,500 ancestry-informative markers. We investigated global genetic ancestry and did a whole genome admixture scan searching for breast cancer–predisposing loci in association with disease phenotypes. We found a significant difference in ancestry between ER+PR+ and ER−PR− women, with higher European ancestry among ER+PR+ individuals, after controlling for possible confounders (odds ratios for a 0 to 1 change in European ancestry proportion, 2.84; 95% confidence interval, 1.13-7.14; P = 0.026). Women with localized tumors had higher European ancestry than women with non–localized tumors (odds ratios, 2.65; 95% confidence interval, 1.11-6.35; P = 0.029). No genome-wide statistically significant associations were observed between European or African ancestry at any specific locus and breast cancer, or in analyses stratified by ER/PR status, stage, or grade. In summary, in African American women, genetic ancestry is associated with ER/PR status and disease stage. However, we found little evidence that genetic ancestry at any one region contributes significantly to breast cancer risk or hormone receptor status. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3110–7)
Data from Impact of Multiple Alcohol Dehydrogenase Gene Polymorphisms on Risk of Upper Aerodigestive Tract Cancers in a Japanese Population
Authors: Oze Isao , Matsuo Keitaro , Suzuki Takeshi , Kawase Takakazu , Watanabe Miki , Hiraki Akio , Ito Hidemi , Hosono Satoyo , Ozawa Taijiro , Hatooka Shunzo , Yatabe Yasuhi , Hasegawa Yasuhisa , Shinoda Masayuki , Kiura Katsuyuki , Tajima Kazuo , Tanimoto Mitsune , Tanaka Hideo
Published: March 2023

Abstract
Alcohol intake is positively associated with the risk of upper aerodigestive tract (UAT) cancer. The genes that encode alcohol-metabolizing enzymes, primarily alcohol dehydrogenases (ADH) and aldehyde dehydrogenases (ALDH), are polymorphic. In Caucasians, significant associations between polymorphisms in ADH1B (rs1229984) and ADH1C (rs698 and rs1693482), and UAT cancer have been observed, despite strong linkage disequilibrium among them. Moreover, UAT cancer was significantly associated with rs1573496 in ADH7, and not with rs1984362 in ADH4. However, little evidence is available concerning ADH4 or ADH7 polymorphisms in Asian populations. We conducted a matched case-control study to clarify the role of ADH polymorphisms in a Japanese population. Cases and controls were 585 patients with UAT cancer and 1,170 noncancer outpatients. Genotyping for ADHs and ALDH2 was done using TaqMan assays. Associations between polymorphisms and UAT cancer were assessed by odds ratios and 95% confidence intervals using conditional logistic regression models that adjusted for age, sex, smoking, drinking, and ALDH2. Adjusted odds ratios were significant for rs4148887 and rs3805322 in ADH4, rs1229984 in ADH1B, rs698 and rs1693482 in ADH1C, and rs284787, rs1154460, and rs3737482 in ADH7. We also observed that ADH7 rs3737482 and ADH4 rs4148887 had independently and statistically significant effects on UAT cancer. The magnitude of effect of these ADH polymorphisms was greater in subjects who were heavy drinkers, heavy smokers, and had esophageal cancer. These findings show that multiple ADH gene polymorphisms were associated with UAT cancer in this Japanese population. Further studies in various ethnicities are required. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3097–102)
Data from High Visfatin Expression in Breast Cancer Tissue Is Associated with Poor Survival
Authors: Lee Yi-Chen , Yang Yi-Hsin , Su Jinu-Huang , Chang Hsueh-Ling , Hou Ming-Feng , Yuan Shyng-Shiou F.
Published: March 2023

Abstract
Background: Adipocytokines, adipocyte-secreted hormones, play a critical role in breast cancer development. The expression of visfatin, a newly discovered adipocytokine, in breast cancer tissues was determined and correlated with patient clinicopathologic variables.

Methods: Visfatin expression in breast cancer tissues was analyzed by immunohistochemistry. Visfatin expression was correlated with clinicopathologic variables as well as recurrence rates, using the χ2 test. The prognostic value of visfatin for disease-free and overall survival was evaluated by Kaplan–Meier estimates, and the significance of differences between curves was evaluated by the log-rank test.

Results: High visfatin expression in breast cancer tissues was significantly correlated with tumor size, estrogen receptor (ER) negativity, and progesterone receptor (PR) negativity. Hormone therapy, but not radiotherapy or chemotherapy, decreased the recurrence rate in patients with high visfatin expression. Whereas high visfatin expression alone was associated with poor disease-free and overall survival, worse disease-free and overall survival was observed when high visfatin expression was combined with ER- and PR-negative status. Cox regression analysis also revealed that visfatin is an independent predictor of disease-free and overall survival.

Conclusion: High visfatin expression in breast cancer tissue is associated with more malignant cancer behavior as well as poor patient survival.

Impact: Visfatin is an independent prognosis predictor for breast cancer. Cancer Epidemiol Biomarkers Prev; 20(9); 1892–901. ©2011 AACR.
Data from Incident Cervical HPV Infections in Young Women: Transition Probabilities for CIN and Infection Clearance
Authors: Insinga Ralph P. , Perez Gonzalo , Wheeler Cosette M. , Koutsky Laura A. , Garland Suzanne M. , Leodolter Sepp , Joura Elmar A. , Ferris Daron G. , Steben Marc , Hernandez-Avila Mauricio , Brown Darron R. , Elbasha Elamin , Muñoz Nubia , Paavonen Jorma , Haupt Richard M.
Published: March 2023

Abstract
Background: We describe transition probabilities for incident human papillomavirus (HPV) 16/18/31/33/35/45/52/58/59 infections and cervical intraepithelial neoplasia (CIN) 1 lesions.

Methods: Women ages 16 to 23 years underwent cytology and cervical swab PCR testing for HPV at approximately 6-month intervals for up to 4 years in the placebo arm of an HPV vaccine trial. The cumulative proportion of incident HPV infections with diagnosed CIN, clearing (infection undetectable), or persisting without CIN, were estimated.

Results: Most incident infections cleared, without detection of CIN, ranging at 36 months from 66.9% for HPV31 to 91.1% for HPV59. There was little variation in the 36-month proportion of incident HPV16, 18, and 31 infections followed by a CIN1 lesion positive for the relevant HPV type (range 16.7%–18.6%), with lower risks for HPV59 (6.4%) and HPV33 (2.9%). Thirty-six–month transition probabilities for CIN2 ranged across types from 2.2% to 9.1%; however, the number of events was generally too small for statistically significant differences to be seen across types for this endpoint, or CIN3.

Conclusions: Some incident HPV types appear more likely to result in diagnosed CIN1 than others. The relative predominance of HPV16, vis-à-vis some other high-risk HPV types (e.g., HPV33) in prevalent CIN2/3, appears more directly associated with relatively greater frequency of incident HPV16 infections within the population, than a higher risk of infection progression to CIN2/3.

Impact: Nearly all incident HPV infections either manifest as detectable CIN or become undetectable within 36 months. Some HPV types (e.g., 16 and 33) appear to have similar risk of CIN2/3 despite widely varied incidence. Cancer Epidemiol Biomarkers Prev; 20(2); 287–96. ©2011 AACR.
Data from Imaging Features of HER2 Overexpression in Breast Cancer: A Systematic Review and Meta-analysis
Authors: Elias Sjoerd G. , Adams Arthur , Wisner Dorota J. , Esserman Laura J. , van't Veer Laura J. , Mali Willem P.Th.M. , Gilhuijs Kenneth G.A. , Hylton Nola M.
Published: March 2023

Abstract
Breast cancer imaging phenotype is diverse and may relate to molecular alterations driving cancer behavior. We systematically reviewed and meta-analyzed relations between breast cancer imaging features and human epidermal growth factor receptor type 2 (HER2) overexpression as a marker of breast cancer aggressiveness. MEDLINE and EMBASE were searched for mammography, breast ultrasound, magnetic resonance imaging (MRI), and/or [18F]fluorodeoxyglucose positron emission tomography studies through February 2013. Of 68 imaging features that could be pooled (85 articles, 23,255 cancers; random-effects meta-analysis), 11 significantly related to HER2 overexpression. Results based on five or more studies and robustness in subgroup analyses were as follows: the presence of microcalcifications on mammography [pooled odds ratio (pOR), 3.14; 95% confidence interval (CI), 2.46–4.00] or ultrasound (mass-associated pOR, 2.95; 95% CI, 2.34–3.71), branching or fine linear microcalcifications (pOR, 2.11; 95% CI, 1.07–4.14) or extremely dense breasts on mammography (pOR, 1.37; 95% CI, 1.07–1.76), and washout (pOR, 1.57; 95% CI, 1.11–2.21) or fast initial kinetics (pOR, 2.60; 95% CI, 1.43–4.73) on MRI all increased the chance of HER2 overexpression. Maximum [18F]fluorodeoxyglucose standardized uptake value (SUVmax) was higher upon HER2 overexpression (pooled mean difference, +0.76; 95% CI, 0.10–1.42). These results show that several imaging features relate to HER2 overexpression, lending credibility to the hypothesis that imaging phenotype reflects cancer behavior. This implies prognostic relevance, which is especially relevant as imaging is readily available during diagnostic work-up. Cancer Epidemiol Biomarkers Prev; 23(8); 1464–83. ©2014 AACR.
Data from Identification of Potential Serum Biomarkers of Glioblastoma: Serum Osteopontin Levels Correlate with Poor Prognosis
Authors: Sreekanthreddy Peddagangannagari , Srinivasan Harish , Kumar Durairaj Mohan , Nijaguna Mamatha Bangalore , Sridevi Sambandam , Vrinda Marigowda , Arivazhagan Arimappamagan , Balasubramaniam Anandh , Hegde Alangar Sathyaranjandas , Chandramouli Bangalore A. , Santosh Vani , Rao Manchanahalli R.S. , Kondaiah Paturu , Somasundaram Kumaravel
Published: March 2023

Abstract
Background: The aim of this study is to identify serum biomarkers with classification and prognosis utility for astrocytoma, in particular glioblastoma (GBM).

Methods: Our previous glioma microarray database was mined to identify genes that encode secreted or membrane-localized proteins. Subsequent analysis was done using significant analysis of microarrays, followed by reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemical validation in tumor tissues, ELISA and Western blot validation in sera, and correlation with survival of GBM patients.

Results: Significant analysis of microarrays identified 31 upregulated and 3 downregulated genes specifically in GBMs. RT-qPCR validation on an independent set of samples confirmed the GBM-specific differential expression of several genes, including three upregulated (CALU, CXCL9, and TIMP1) and two downregulated (GPX3 and TIMP3) novel genes. With respect to osteopontin (OPN), we show the GBM-specific upregulation by RT-qPCR and immunohistochemical staining of tumor tissues. Elevated serum OPN levels in GBM patients were also shown by ELISA and Western blot. GBM patients with high serum OPN levels had poorer survival than those with low serum OPN levels (median survival 9 versus 22 months respectively; P = 0.0001). Further, we also show high serum TIMP1 levels in GBM patients compared with grade II/III patients by ELISA and downregulation of serum GPX3 and TIMP3 proteins in GBMs compared with normal control by Western blot analysis.

Conclusions: Several novel potential serum biomarkers of GBM are identified and validated. High serum OPN level is found as a poor prognostic indicator in GBMs.

Impact: Identified serum biomarkers may have potential utility in astrocytoma classification and GBM prognosis. Cancer Epidemiol Biomarkers Prev; 19(6); 1409–22. ©2010 AACR.
Data from Biomarkers Related to One-Carbon Metabolism as Potential Risk Factors for Distal Colorectal Adenomas
Authors: de Vogel Stefan , Schneede Jörn , Ueland Per Magne , Vollset Stein Emil , Meyer Klaus , Fredriksen Åse , Midttun Øivind , Bjørge Tone , Kampman Ellen , Bretthauer Michael , Hoff Geir
Published: March 2023

Abstract
Background: Efficient one-carbon metabolism, which requires adequate supply of methyl group donors and B-vitamins, may protect against colorectal carcinogenesis. However, plasma folate and vitamins B2 and B12 have inconsistently been associated with colorectal cancer risk, and there have been no previous studies relating plasma concentrations of methionine, choline, and betaine to this outcome.

Methods: This study comprised 10,601 individuals, 50 to 64 years of age, participating in the Norwegian Colorectal Cancer Prevention (NORCCAP) screening study. Using logistic regression analyses, we crosssectionally investigated associations between distal colorectal adenoma occurrence–potential precursor lesions of colorectal carcinomas–and plasma concentrations of methyl group donors and B-vitamins, and polymorphisms of genes related to one-carbon metabolism.

Results: Screening revealed 1,809 subjects (17.1%) with at least one adenoma. The occurrence of high-risk adenomas (observed in 421 subjects) was inversely associated with plasma concentrations of methionine (highest versus lowest quartile: odds ratio (OR) = 0.61; 95% confidence interval (CI) = 0.45–0.83), betaine: OR = 0.74; 95% CI = 0.54–1.02, the vitamin B2 form flavin-mononucleotide (FMN): OR = 0.65; 95% CI = 0.49–0.88, and the vitamin B6 form pyridoxal 5′-phosphate (PLP): OR = 0.69; 95% CI = 0.51–0.95, but not with folate, choline, vitamin B12 concentrations, or with the studied polymorphisms. High methionine concentration in combination with high vitamin B2 or B6 concentrations was associated with lower occurrence of high-risk adenomas compared with these factors individually.

Conclusions: High plasma concentrations of methionine and betaine, and vitamins B2 and B6 may reduce risk of developing colorectal adenomas.

Impact: In addition to B-vitamins, methyl group donors such as methionine and betaine may play a role in colorectal carcinogenesis. Cancer Epidemiol Biomarkers Prev; 20(8); 1726–35. ©2011 AACR.
Data from High-Throughput Simultaneous Analysis of Five Urinary Metabolites of Areca Nut and Tobacco Alkaloids by Isotope-Dilution Liquid Chromatography-Tandem Mass Spectrometry with On-Line Solid-Phase Extraction
Authors: Hu Chiung-Wen , Chang Yan-Zin , Wang Hsiao-Wen , Chao Mu-Rong
Published: March 2023

Abstract
Background: Areca nut and tobacco are commonly used drugs worldwide and have been frequently used in combination. We describe the use of on-line solid-phase extraction and isotope-dilution liquid chromatography-tandem mass spectrometry for the simultaneous measurement of five major urinary metabolites of both areca nut and tobacco alkaloids, namely, arecoline, arecaidine, N-methylnipecotic acid, nicotine, and cotinine.

Methods: Automated purification of urine was accomplished with a column-switching device. After the addition of deuterium-labeled internal standards, urine samples were directly analyzed within 13 minutes. This method was applied to measure urinary metabolites in 90 healthy subjects to assess areca nut/tobacco exposure. Urinary time course of arecoline, arecaidine, and N-methylnipecotic acid was investigated in five healthy nonchewers after oral administration of areca nut water extracts.

Results: The limits of detection were 0.016 to 0.553 ng/mL. Interday and intraday imprecision were <10%. Mean recoveries of five metabolites in urine were 97% to 114%. Mean urinary concentrations of arecoline, arecaidine, N-methylnipecotic acid, nicotine, and cotinine in regular areca nut chewers also smokers were 23.9, 5,816, 1,298, 2,635, and 1,406 ng/mg creatinine, respectively. Time course study revealed that after administration of areca nuts extracts, the major urinary metabolite was arecaidine with a half-life of 4.3 hours, followed by N-methylnipecotic acid with a half-life of 7.9 hours, and very low levels of arecoline with a half-life of 0.97 hour.

Conclusions: This on-line solid-phase extraction liquid chromatography-tandem mass spectrometry method firstly provides high-throughput direct analysis of five urinary metabolites of areca nut/tobacco alkaloids.

Impact: This method may facilitate the research into the oncogenic effects of areca nut/tobacco exposure. Cancer Epidemiol Biomarkers Prev; 19(10); 2570–81. ©2010 AACR.
Data from Subtype-Specific Risk of Testicular Tumors among Immigrants and Their Descendants in Sweden, 1960 to 2007
Authors: Beiki Omid , Granath Fredrik , Allebeck Peter , Akre Olof , Moradi Tahereh
Published: March 2023

Abstract
Background: Testicular cancer is the most common cancer among young male adults in several populations. We compared subtype-specific risk of testicular cancer among migrants and their descendants to that of Swedish-born men to elucidate importance of genetic and environmental factors in testicular cancer etiology and the potential timing of exposures.

Methods: We followed a nationwide cohort of 3.6 million men ages 15 to 54 years between 1960 and 2007 through linkage between Swedish National Registers. Incidence rate ratio (IRR) adjusted for age and calendar year with 95% confidence intervals (CI) was estimated using Poisson regression.

Results: A total of 5,801 cases of testicular cancer occurred during 80 million person-years of follow-up. Compared with Swedish-born men, first-generation immigrants from low-risk countries had a lower risk (IRR, 0.43; 95% CI, 0.38-0.49) and first-generation immigrants from high-risk countries had a higher risk (IRR, 1.61; 95% CI, 1.42-1.83) of testicular cancer. The risk among first-generation immigrants varied remarkably by birthplace, reflecting the risk in their countries of birth. The risk of seminomas was statistically significantly modified by age at immigration and duration of residence among immigrants born in high-risk areas. We observed a statistically significantly convergence of risk among second-generation immigrants toward the risk in Sweden (IRR, 1.02; 95% CI, 0.93-1.12). The risk among second-generation immigrants was not affected by the duration of stay of their mothers in Sweden before pregnancy.

Conclusions: Our study provides evidence that life-style and environmental factors play an important role in the etiology of testicular cancer. Cancer Epidemiol Biomarkers Prev; 19(4); 1053–65. ©2010 AACR.
Data from Surveillance Methods for Identifying, Characterizing, and Monitoring Tobacco Products: Potential Reduced Exposure Products as an Example
Authors: O'Connor Richard J. , Cummings K. Michael , Rees Vaughan W. , Connolly Gregory N. , Norton Kaila J. , Sweanor David , Parascandola Mark , Hatsukami Dorothy K. , Shields Peter G.
Published: March 2023

Abstract
Tobacco products are widely sold and marketed, yet integrated data systems for identifying, tracking, and characterizing products are lacking. Tobacco manufacturers recently have developed potential reduced exposure products (PREP) with implied or explicit health claims. Currently, a systematic approach for identifying, defining, and evaluating PREPs sold at the local, state, or national levels in the United States has not been developed. Identifying, characterizing, and monitoring new tobacco products could be greatly enhanced with a responsive surveillance system. This article critically reviews available surveillance data sources for identifying and tracking tobacco products, including PREPs, evaluating strengths and weaknesses of potential data sources in light of their reliability and validity. With the absence of regulations mandating disclosure of product-specific information, it is likely that public health officials will need to rely on a variety of imperfect data sources to help identify, characterize, and monitor tobacco products, including PREPs. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3334–48)
Data from Chlamydia pneumoniae Infection and Risk for Lung Cancer
Authors: Chaturvedi Anil K. , Gaydos Charlotte A. , Agreda Patricia , Holden Jeffrey P. , Chatterjee Nilanjan , Goedert James J. , Caporaso Neil E. , Engels Eric A.
Published: March 2023

Abstract
Background: We evaluated the relationship of Chlamydia pneumoniae infection with prospective lung cancer risk using traditional serologic markers [microimmunoflourescence (MIF) IgG and IgA antibodies] and Chlamydia heat shock protein-60 (CHSP-60) antibodies, a marker for chronic chlamydial infection.

Methods: We conducted a nested case-control study (593 lung cancers and 671 controls) within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 77,464). Controls were matched to cases by age, sex, randomization year, follow-up time, and smoking (pack-years of smoking, time since quitting). We assessed C. pneumoniae seropositivity and endpoint antibody titers (IgG and IgA against C. pneumoniae elementary bodies and IgG against CHSP-60).

Results: C. pneumoniae seropositivity by microimmunoflourescence IgG or IgA antibodies was not associated with lung cancer [odds ratio of 0.88 and 95% confidence interval (95% CI) of 0.69-1.13 for IgG; odds ratio of 0.98 and 95% CI of 0.75-1.27 for IgA]. In contrast, individuals seropositive for CHSP-60 IgG antibodies had significantly increased lung cancer risk (odds ratio, 1.30; 95% CI, 1.02-1.67), and risk increased with increasing antibody titers (P trend = 0.006). CHSP-60–related risk did not differ significantly by lung cancer histology, follow-up time, or smoking. CHSP-60 seropositivity was associated with increased risk 2 to 5 years before lung cancer diagnosis (odds ratio, 1.77; 95% CI, 1.16-2.71; P trend = 0.006), thus arguing against reverse causality.

Conclusions: CHSP-60 seropositivity and elevated antibody titers were associated with significantly increased risk for subsequent lung cancer, supporting an etiologic role for C. pneumoniae infection in lung carcinogenesis.

Impact: Our results highlight the potential for lung cancer risk reduction through treatments targeted toward C. pneumoniae infections and chronic pulmonary inflammation. Cancer Epidemiol Biomarkers Prev; 19(6); 1498–505. ©2010 AACR.
Data from Exposure to Smoking Imagery in the Movies and Experimenting with Cigarettes among Mexican Heritage Youth
Authors: Wilkinson Anna V. , Spitz Margaret R. , Prokhorov Alexander V. , Bondy Melissa L. , Shete Sanjay , Sargent James D.
Published: March 2023

Abstract
There is growing evidence that an adolescent's decision to try cigarettes is influenced by level of exposure to movies in which smoking is portrayed. Less is known about how ethnicity affects this process. We examined whether acculturation and/or country of birth influence the relationship between exposure to smoking imagery in the movies and experimenting with cigarettes among Mexican origin youth. We prospectively followed 1,328 Mexican origin adolescents ages 11 to 13 years at baseline. We assessed which of 50 movies (randomly selected from a pool of 250 popular contemporary movies released from 1999 to 2004 and content analyzed for smoking) adolescents had seen. Smoking behavior was assessed at baseline and at 6-month intervals over 24 months. Ten percent of the adolescents had experimented at baseline; 17% tried subsequently. Multivariate analyses revealed, as exposure to smoking imagery in the movies increased, the chances of having ever experimented [adjusted odds ratio (AOR) = 1.27; 95% confidence interval (CI), 1.10-1.48] and of being a new experimenter (AOR = 1.19; 95% CI, 1.01-1.40) increased, equivalent to a 4.2% increased risk of ever and a 3.0% increased risk of new experimenting for each additional quartile of movie exposure. This effect was moderated by country of birth. For Mexican-born youth, exposure to smoking imagery in the movies was the strongest independent predictor of new experimentation (AOR = 1.52; 95% CI, 1.14-2.05). For U.S.-born youth, we observed a ceiling effect: the percent of experimenters increased with increasing exposure, and then flattened. Among Mexican-born youth, exposure to smoking imagery in the movies may be an important part of the acculturation process associated with smoking initiation. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3435–43)
Data from Comparison of Mammographic Density Assessed as Volumes and Areas among Women Undergoing Diagnostic Image-Guided Breast Biopsy
Authors: Gierach Gretchen L. , Geller Berta M. , Shepherd John A. , Patel Deesha A. , Vacek Pamela M. , Weaver Donald L. , Chicoine Rachael E. , Pfeiffer Ruth M. , Fan Bo , Mahmoudzadeh Amir Pasha , Wang Jeff , Johnson Jason M. , Herschorn Sally D. , Brinton Louise A. , Sherman Mark E.
Published: March 2023

Abstract
Background: Mammographic density (MD), the area of non–fatty-appearing tissue divided by total breast area, is a strong breast cancer risk factor. Most MD analyses have used visual categorizations or computer-assisted quantification, which ignore breast thickness. We explored MD volume and area, using a volumetric approach previously validated as predictive of breast cancer risk, in relation to risk factors among women undergoing breast biopsy.

Methods: Among 413 primarily white women, ages 40 to 65 years, undergoing diagnostic breast biopsies between 2007 and 2010 at an academic facility in Vermont, MD volume (cm3) was quantified in craniocaudal views of the breast contralateral to the biopsy target using a density phantom, whereas MD area (cm2) was measured on the same digital mammograms using thresholding software. Risk factor associations with continuous MD measurements were evaluated using linear regression.

Results: Percent MD volume and area were correlated (r = 0.81) and strongly and inversely associated with age, body mass index (BMI), and menopause. Both measures were inversely associated with smoking and positively associated with breast biopsy history. Absolute MD measures were correlated (r = 0.46) and inversely related to age and menopause. Whereas absolute dense area was inversely associated with BMI, absolute dense volume was positively associated.

Conclusions: Volume and area MD measures exhibit some overlap in risk factor associations, but divergence as well, particularly for BMI.

Impact: Findings suggest that volume and area density measures differ in subsets of women; notably, among obese women, absolute density was higher with volumetric methods, suggesting that breast cancer risk assessments may vary for these techniques. Cancer Epidemiol Biomarkers Prev; 23(11); 2338–48. ©2014 AACR.
Data from Association of Insulin-Related Serum Factors with Colorectal Polyp Number and Type in Adult Males
Authors: Comstock Sarah S. , Xu Diana , Hortos Kari , Kovan Bruce , McCaskey Sarah , Pathak Dorothy R. , Fenton Jenifer I.
Published: March 2023

Abstract
Background: Dysregulated insulin signaling is thought to contribute to cancer risk.

Methods: To determine if insulin-related serum factors are associated with colon polyps, 126 asymptomatic men (48–65 years) were recruited at colonoscopy. Blood was collected. Odds ratios were determined using polytomous logistic regression for polyp number and type.

Results: Males with serum C-peptide concentration >3.3 ng/mL were 3.8 times more likely to have an adenoma relative to no polyp than those with C-peptide ≤1.8 ng/mL. As C-peptide tertile increased, an individual was 2 times more likely to have an adenoma (P = 0.01) than no polyp. There were no associations between insulin-like growth factor or its binding proteins with polyp number or type. Males with soluble receptor for advanced glycation end products (sRAGE) concentration >120.4 pg/mL were 0.25 times less likely to have ≥3 polyps relative to no polyps compared with males with sRAGE ≤94.5 pg/mL. For each increase in sRAGE tertile, a man was 0.5 times less likely to have ≥3 polyps than no polyps (P = 0.03). Compared with males with a serum vascular endothelial growth factor (VEGF) concentration ≤104.7 pg/mL, males with a serum VEGF concentration >184.2 pg/mL were 3.4 times more likely to have ≥3 polyps relative to no polyps. As the VEGF tertile increased, a man was 1.9 times more likely to have ≥3 polyps than no polyps (P = 0.049).

Conclusions: Serum concentrations of C-peptide, sRAGE, and VEGF may indicate which men could benefit most from colonoscopy.

Impact: Identification of biomarkers could reduce medical costs through the elimination of colonoscopies on low-risk individuals. Cancer Epidemiol Biomarkers Prev; 23(9); 1843–51. ©2014 AACR.
Data from A Segregation Analysis of Barrett's Esophagus and Associated Adenocarcinomas
Authors: Sun Xiangqing , Elston Robert , Barnholtz-Sloan Jill , Falk Gary , Grady William M. , Kinnard Margaret , Mittal Sumeet K. , Willis Joseph E. , Markowitz Sanford , Brock Wendy , Chak Amitabh
Published: March 2023

Abstract
Familial aggregation of esophageal adenocarcinomas, esophagogastric junction adenocarcinomas, and their precursor Barrett's esophagus (BE) has been termed familial BE (FBE). Numerous studies documenting increased familial risk for these diseases raise the hypothesis that there may be an inherited susceptibility to the development of BE and its associated cancers. In this study, using segregation analysis for a binary trait as implemented in S.A.G.E. 6.0.1, we analyzed data on 881 singly ascertained pedigrees to determine whether FBE is caused by a common environmental or genetic agent and, if genetic, to identify the mode of inheritance of FBE. The inheritance models were compared by likelihood ratio tests and Akaike's A Information Criterion. Results indicated that random environmental and/or multifactorial components were insufficient to fully explain the familial nature of FBE, but rather, there is segregation of a major type transmitted from one generation to the next (P < 10−10). An incompletely dominant inheritance model together with a polygenic component fits the data best. For this dominant model, the estimated penetrance of the dominant allele is 0.1005 [95% confidence interval (95% CI), 0.0587-0.1667] and the sporadic rate is 0.0012 (95% CI, 0.0004-0.0042), corresponding to a relative risk of 82.53 (95% CI, 28.70-237.35) or odds ratio of 91.63 (95% CI, 32.01-262.29). This segregation analysis provides epidemiologic evidence in support of one or more rare autosomally inherited dominant susceptibility allele(s) in FBE families and, hence, motivates linkage analyses. Cancer Epidemiol Biomarkers Prev; 19(3); 666–74