bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Efficacy of Exercise Interventions in Modulating Cancer-Related Fatigue among Adult Cancer Survivors: A Meta-Analysis
Authors: Brown Justin C. , Huedo-Medina Tania B. , Pescatello Linda S. , Pescatello Shannon M. , Ferrer Rebecca A. , Johnson Blair T.
Published: March 2023

Abstract
Background: The purpose of this meta-analysis was to explore the efficacy of exercise as a nonpharmacologic intervention to reduce cancer-related fatigue (CRF) among adult cancer survivors. We also investigated how different components of the exercise prescription (Ex Rx), methodologic considerations, and subject characteristics modulate CRF.

Methods: A systematic search for randomized controlled trials was conducted using words related to cancer, exercise, and fatigue.

Results: In total, 44 studies with 48 interventions qualified, including 3,254 participants of varying cancer types, stages of diagnosis, treatments, and exercise interventions. Cancer survivors in exercise interventions reduced their CRF levels to a greater extent than usual care controls, d+ = 0.31 (95% CI = 0.22–0.40), an effect that appeared to generalize across several types of cancer. CRF levels improved in direct proportion to the intensity of resistance exercise (β = 0.60, P = 0.01), a pattern that was stronger in higher quality studies (β = 0.23, P < 0.05). CRF levels also reduced to a greater extent when interventions were theoretically driven (β = 0.48, P < 0.001) or cancer survivors were older (β = 0.24, P = 0.04).

Conclusions: Exercise reduced CRF especially in programs that involved moderate-intensity, resistance exercise among older cancer survivors and that were guided by theory.

Impact: Our results indicate exercise interventions for adult cancer survivors should be multi-dimensional and individualized according to health outcome and cancer type. Cancer Epidemiol Biomarkers Prev; 20(1); 123–33. ©2011 AACR.
Data from What If I Don't Treat My PSA-Detected Prostate Cancer? Answers from Three Natural History Models
Authors: Gulati Roman , Wever Elisabeth M. , Tsodikov Alex , Penson David F. , Inoue Lurdes Y.T. , Katcher Jeffrey , Lee Shih-Yuan , Heijnsdijk Eveline A.M. , Draisma Gerrit , de Koning Harry J. , Etzioni Ruth
Published: March 2023

Abstract
Background: Making an informed decision about treating a prostate cancer detected after a routine prostate-specific antigen (PSA) test requires knowledge about disease natural history, such as the chances that it would have been clinically diagnosed in the absence of screening and that it would metastasize or lead to death in the absence of treatment.

Methods: We use three independently developed models of prostate cancer natural history to project risks of clinical progression events and disease-specific deaths for PSA-detected cases assuming they receive no primary treatment.

Results: The three models project that 20%–33% of men have preclinical onset; of these 38%–50% would be clinically diagnosed and 12%–25% would die of the disease in the absence of screening and primary treatment. The risk that men age less than 60 at PSA detection with Gleason score 2–7 would be clinically diagnosed in the absence of screening is 67%–93% and would die of the disease in the absence of primary treatment is 23%–34%. For Gleason score 8 to 10 these risks are 90%–96% and 63%–83%.

Conclusions: Risks of disease progression among untreated PSA-detected cases can be nontrivial, particularly for younger men and men with high Gleason scores. Model projections can be useful for informing decisions about treatment.

Impact: This is the first study to project population-based natural history summaries in the absence of screening or primary treatment and risks of clinical progression events following PSA detection in the absence of primary treatment. Cancer Epidemiol Biomarkers Prev; 20(5); 740–50. ©2011 AACR.
Data from Variation in Mutation Spectrum Partly Explains Regional Differences in the Breast Cancer Risk of Female BRCA Mutation Carriers in the Netherlands
Authors: Vos Janet R. , Teixeira Natalia , van der Kolk Dorina M. , Mourits Marian J.E. , Rookus Matti A. , van Leeuwen Flora E. , Collée Margriet , van Asperen Christi J. , Mensenkamp Arjen R. , Ausems Margreet G.E.M. , van Os Theo A.M. , Meijers-Heijboer Hanne E.J. , Gómez-Garcia Encarna B. , Vasen Hans F. , Brohet Richard M. , van der Hout Annemarie H. , Jansen Liesbeth , Oosterwijk Jan C. , de Bock Geertruida H.
Published: March 2023

Abstract
Background: We aimed to quantify previously observed relatively high cancer risks in BRCA2 mutation carriers (BRCA2 carriers) older than 60 in the Northern Netherlands, and to analyze whether these could be explained by mutation spectrum or population background risk.

Methods: This consecutive cohort study included all known pathogenic BRCA1/2 carriers in the Northern Netherlands (N = 1,050). Carrier and general reference populations were: BRCA1/2 carriers in the rest of the Netherlands (N = 2,013) and the general population in both regions. Regional differences were assessed with HRs and ORs. HRs were adjusted for birth year and mutation spectrum.

Results: All BRCA1 carriers and BRCA2 carriers younger than 60 had a significantly lower breast cancer risk in the Northern Netherlands; HRs were 0.66 and 0.64, respectively. Above age 60, the breast cancer risk in BRCA2 carriers in the Northern Netherlands was higher than in the rest of the Netherlands [HR, 3.99; 95% confidence interval (CI), 1.11–14.35]. Adjustment for mutational spectrum changed the HRs for BRCA1, BRCA2 <60, and BRCA2 ≥60 years by −3%, +32%, and +11% to 0.75, 0.50, and 2.61, respectively. There was no difference in background breast cancer incidence between the two regions (OR, 1.03; 95% CI, 0.97–1.09).

Conclusions: Differences in mutation spectrum only partly explain the regional differences in breast cancer risk in BRCA2 carriers, and for an even smaller part in BRCA1 carriers.

Impact: The increased risk in BRCA2 carriers older than 60 may warrant extension of intensive breast screening beyond age 60. Cancer Epidemiol Biomarkers Prev; 23(11); 2482–91. ©2014 AACR.
Data from Biomarkers for Early Detection of Colorectal Cancer and Polyps: Systematic Review
Authors: Shah Reena , Jones Emma , Vidart Victoire , Kuppen Peter J.K. , Conti John A. , Francis Nader K.
Published: March 2023

Abstract
There is growing interest in early detection of colorectal cancer as current screening modalities lack compliance and specificity. This study systematically reviewed the literature to identify biomarkers for early detection of colorectal cancer and polyps. Literature searches were conducted for relevant papers since 2007. Human studies reporting on early detection of colorectal cancer and polyps using biomarkers were included. Methodologic quality was evaluated, and sensitivity, specificity, and the positive predictive value (PPV) were reported. The search strategy identified 3,348 abstracts. A total of 44 papers, examining 67 different tumor markers, were included. Overall sensitivities for colorectal cancer detection by fecal DNA markers ranged from 53% to 87%. Combining fecal DNA markers increased the sensitivity of colorectal cancer and adenoma detection. Canine scent detection had a sensitivity of detecting colorectal cancer of 99% and specificity of 97%. The PPV of immunochemical fecal occult blood test (iFOBT) is 1.26%, compared with 0.31% for the current screening method of guaiac fecal occult blood test (gFOBT). A panel of serum protein biomarkers provides a sensitivity and specificity above 85% for all stages of colorectal cancer, and a PPV of 0.72%. Combinations of fecal and serum biomarkers produce higher sensitivities, specificities, and PPVs for early detection of colorectal cancer and adenomas. Further research is required to validate these biomarkers in a well-structured population-based study. Cancer Epidemiol Biomarkers Prev; 23(9); 1712–28. ©2014 AACR.
Data from Associations of Lifestyle Factors and Anthropometric Measures with Repeat PSA Levels During Active Surveillance/Monitoring
Authors: Burton Anya J. , Martin Richard M. , Donovan Jenny L. , Lane J. Athene , Davis Michael , Hamdy Freddie C. , Neal David E. , Tilling Kate
Published: March 2023

Abstract
Background: Assessment of prostate-specific antigen increase with time (PSA growth) is a fundamental component of active surveillance among men with localized prostate cancer. Factors that influence PSA growth, however, are unclear. We evaluated associations of anthropometric and lifestyle factors with age-related PSA growth.

Methods: Repeat PSA measures from 404 men, aged 50 to 69 years, with localized prostate cancer undergoing active monitoring were obtained. From log(PSA) measures, age-specific multilevel mixed effect linear models were developed to predict PSA at age 50 years and yearly increase in postdiagnosis PSA. Baseline anthropometric measures, alcohol consumption, occupational class, smoking status, and physical activity were added to the model as covariates.

Results: The median number of repeat PSAs was 13 (range, 2–40), and the mean duration of follow-up was 4.8 years (SD, 2.3). The basic model of age-related PSA growth in men with localized prostate cancer estimated a mean PSA at age 50 of 3.95 ng/mL [95% confidence interval (CI): 3.55 to 4.39] and a yearly increase of 8.50% (95% CI: 7.90% to 9.10%). PSA at age 50 years was 2.1% lower per unit increase in weighted exercise score (95% CI: −3.3 to −0.8), 5.3% lower per 5 cm increase in height (95% CI: −9.4 to −1.1), and 24.5% higher (95% CI: 4.0 to 49.1) in current smokers than never smokers. Similar associations with PSA growth were seen.

Conclusion: Smoking and exercise are modifiable lifestyle factors that may be associated with PSA levels in men with localized prostate cancer undergoing active monitoring/surveillance.

Impact: These factors may be useful in understanding etiology of progression. Cancer Epidemiol Biomarkers Prev; 21(10); 1877–85. ©2012 AACR.
Data from Variations in Chromosomes 9 and 6p21.3 with Risk of Non–Hodgkin Lymphoma
Authors: Wang Sophia S. , Menashe Idan , Cerhan James R. , Cozen Wendy , Severson Richard K. , Davis Scott , Hutchinson Amy , Rothman Nathaniel , Chanock Stephen J. , Bernstein Leslie , Hartge Patricia , Morton Lindsay M.
Published: March 2023

Abstract
Background: There is growing evidence linking genetic variations to non–Hodgkin lymphoma (NHL) etiology. To complement ongoing agnostic approaches for identifying susceptibility genes, we evaluated 488 candidate gene regions and their relation to risk for NHL and NHL subtypes.

Methods: We genotyped 6,679 tag single nucleotide polymorphisms (SNPs) in 947 cases and 826 population-based controls from a multicenter U.S. case–control study. Gene-level summary of associations were obtained by computing the minimum P value (“minP test”) on the basis of 10,000 permutations. We used logistic regression to evaluate the association between genotypes and haplotypes with NHL. For NHL subtypes, we conducted polytomous multivariate unconditional logistic regression (adjusted for sex, race, age). We calculated P-trends under the codominant model for each SNP.

Results: Fourteen gene regions were associated with NHL (P < 0.01). The most significant SNP associated with NHL maps to the SYK gene (rs2991216, P-trend = 0.00005). The three most significant gene regions were on chromosome 6p21.3 (RING1/RXRB; AIF1; BAT4). Accordingly, SNPs in RING1/RXRB (rs2855429), AIF1 (rs2857597), and BAT4 (rs3115667) were associated with NHL (P-trends ≤ 0.0002) and both diffuse large B-cell and follicular lymphomas (P-trends < 0.05).

Conclusions: Our results suggest potential importance for SYK on chromosome 9 with NHL etiology. Our results further implicate 6p21.3 gene variants, supporting the need for full characterization of this chromosomal region in relation to lymphomagenesis.

Impact: Gene variants on chromosome 9 may represent a new region of interesting for NHL etiology. The independence of the reported variants in 6p21.3 from implicated variants (TNF/HLA) supports the need to confirm causal variants in this region Cancer Epidemiol Biomarkers Prev; 20(1); 42–9. ©2011 AACR.
Data from Prediagnostic Circulating Anti-Müllerian Hormone Concentrations Are Not Associated with Prostate Cancer Risk
Authors: Sklavos Martha M. , Zhou Cindy Ke , Pinto Ligia A. , Cook Michael B.
Published: March 2023

Abstract
Despite considerable research, the pathogenesis of prostate cancer remains poorly understood. Meanwhile, PSA testing has shifted prostate cancer case populations for study to include a greater proportion of asymptomatic and indolent disease. Thus, efforts to identify prostate cancer biomarkers—particularly for aggressive disease—are required to elucidate pathogenesis and aid screening efficacy. Current evidence suggests that decreased circulating concentrations of the testis-derived, TGFβ family peptide hormone—anti-Müllerian hormone (AMH)—may be associated with prostate cancer pathogenesis. To test this hypothesis, we measured AMH concentrations in prediagnostic (cohort baseline) sera using the Beckman Coulter AMH Gen II ELISA in 1,000 cases and 1,000 controls nested within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Controls were frequency matched to cases on age at entry, enrollment year, and years of follow-up. Unconditional logistic regression models, adjusted for age at randomization, were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). We found that prediagnostic serologic AMH concentrations were not significantly associated with total (ORQ4 vs. Q1 = 1.15; 95% CI, 0.89–1.48; Ptrend = 0.13), aggressive (ORQ4 vs. Q1 = 1.14; 95% CI, 0.80–1.63; Ptrend = 0.51), or nonaggressive (ORQ4 vs. Q1 = 1.22; 95% CI, 0.91–1.63; Ptrend = 0.07) prostate cancer risks. Different definitions of aggressive disease did not meaningfully alter these results. Despite in vitro studies linking AMH to prostate cancer, this first analysis of prediagnostic, circulating AMH concentrations in men provides no evidence for an association with prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 23(11); 2597–602. ©2014 AACR.
Data from Genetic Polymorphisms in Adaptive Immunity Genes and Childhood Acute Lymphoblastic Leukemia
Authors: Chang Jeffrey S. , Wiemels Joseph L. , Chokkalingam Anand P. , Metayer Catherine , Barcellos Lisa F. , Hansen Helen M. , Aldrich Melinda C. , Guha Neela , Urayama Kevin Y. , Scélo Ghislaine , Green Janet , May Suzanne L. , Kiley Vincent A. , Wiencke John K. , Buffler Patricia A.
Published: March 2023

Abstract
Background: Childhood acute lymphoblastic leukemia (ALL) has been hypothesized to have an infection- and immune-related etiology. The lack of immune priming in early childhood may result in abnormal immune responses to infections later in life and increase ALL risk.

Methods: The current analyses examined the association between childhood ALL and 208 single-nucleotide polymorphisms (SNP) of 29 adaptive immune function genes among 377 ALL cases and 448 healthy controls. Single SNPs were analyzed with a log-additive approach using logistic regression models adjusted for sex, age, Hispanic ethnicity, and race. Sliding window haplotype analyses were done with haplotypes consisting of 2 to 6 SNPs.

Results: Of the 208 SNPs, only rs583911 of IL12A, which encodes a critical modulator of T-cell development, remained significant after accounting for multiple testing (odds ratio for each copy of the variant G allele, 1.52; 95% confidence interval, 1.25-1.85; P = 2.9 × 10−5). This increased risk was stronger among firstborn children of all ethnicities and among non-Hispanic children with less day care attendance, consistent with the hypothesis about the role of early immune modulation in the development of childhood ALL. Haplotype analyses identified additional regions of CD28, FCGR2, GATA3, IL2RA, STAT4, and STAT6 associated with childhood ALL.

Conclusion: Polymorphisms of genes on the adaptive immunity pathway are associated with childhood ALL risk.

Impact: Results of this study support an immune-related etiology of childhood ALL. Further confirmation is required to detect functional variants in the significant genomic regions identified in this study, in particular for IL12A. Cancer Epidemiol Biomarkers Prev; 19(9); 2152–63. ©2010 AACR.
Data from A Prospective Cohort Study of Body Size and Risk of Head and Neck Cancers in the NIH–AARP Diet and Health Study
Authors: Etemadi Arash , O'Doherty Mark G. , Freedman Neal D. , Hollenbeck Albert R. , Dawsey Sanford M. , Abnet Christian C.
Published: March 2023

Abstract
Background: The association between body size and head and neck cancers (HNCA) is unclear, partly because of the biases in case–control studies.

Methods: In the prospective NIH–AARP cohort study, 218,854 participants (132,288 men and 86,566 women), aged 50 to 71 years, were cancer free at baseline (1995 and 1996), and had valid anthropometric data. Cox proportional hazards regression was used to examine the associations between body size and HNCA, adjusted for current and past smoking habits, alcohol intake, education, race, and fruit and vegetable consumption, and reported as HR and 95% confidence intervals (CI).

Results: Until December 31, 2006, 779 incident HNCAs occurred: 342 in the oral cavity, 120 in the oro- and hypopharynx, 265 in the larynx, 12 in the nasopharynx, and 40 at overlapping sites. There was an inverse association between HNCA and body mass index, which was almost exclusively among current smokers (HR = 0.76 per each 5 U increase; 95% CI, 0.63–0.93), and diminished as initial years of follow-up were excluded. We observed a direct association with waist-to-hip ratio (HR = 1.16 per 0.1 U increase; 95% CI, 1.03–1.31), particularly for cancers of the oral cavity (HR, 1.40; 95% CI, 1.17–1.67). Height was also directly associated with total HNCAs (P = 0.02), and oro- and hypopharyngeal cancers (P < 0.01).

Conclusions: The risk of HNCAs was associated inversely with leanness among current smokers, and directly with abdominal obesity and height.

Impact: Our study provides evidence that the association between leanness and risk of HNCAs may be due to effect modification by smoking. Cancer Epidemiol Biomarkers Prev; 23(11); 2422–9. ©2014 AACR.
Data from Demographic Disparities in Patterns of Care and Survival Outcomes for Patients with Resected Gastric Adenocarcinoma
Authors: Stessin Alexander M. , Sherr David L.
Published: March 2023

Abstract
Background: Several reports showed incomplete adoption of adjuvant radiotherapy (RT) for resectable gastric cancer since the publication of Intergroup 0116 trial results. The aims of this study were to identify demographic factors associated with omission of adjuvant RT and assess the impact of this omission on survival.

Methods: SEER database was queried for cases of resected gastric cancer. Multivariate analyses with logistic and Cox regressions were used to examine (a) likelihood of receiving adjuvant RT for different patient and county demographics and (b) effect of demographics on survival outcomes.

Results: A total of 7,348 patients met the study criteria. Adjuvant RT was used in 33.1% of cases diagnosed in 1998–2001 and in 45.3% of cases in 2002–2007 (P < 0.001). Controlling for independent covariates, African Americans were 8.9% less likely to receive adjuvant RT than Caucasians or Asians (P < 0.001). Correspondingly, overall survival rates were significantly lower for African Americans than other races (HR = 1.38, P < 0.001). Furthermore, both the likelihood of receiving RT and the survival rates were significantly affected by county demographics: percent of population without high school education, percent of households below the poverty line, and median household income. Survival rates were highest among Asians, but this finding did not reflect more frequent use of RT.

Conclusions: Race and socioeconomic factors are significant predictors of treatment and survival outcomes for patients with resectable gastric cancer.

Impact: The findings of this and similar studies may aide the medical community in designing more effective strategies to ameliorate the standards of care nationwide. Cancer Epidemiol Biomarkers Prev; 20(2); 223–33. ©2011 AACR.
Data from Analytical Comparison of Three Quantitative Immunochemical Fecal Occult Blood Tests for Colorectal Cancer Screening
Authors: Guittet Lydia , Guillaume Elodie , Levillain Romuald , Beley Philippe , Tichet Jean , Lantieri Olivier , Launoy Guy
Published: March 2023

Abstract
Background: The superiority of several immunochemical fecal occult blood tests (I-FOBT) over guaiac-based tests in colorectal cancer screening is now established. The aim of this study was to compare the analytical performance of 3 quantitative I-FOBTs.

Methods: Stool samples from 10 healthy volunteers, initially I-FOBT negative, supplemented with human blood, were used to compare reproducibility and stability of measurement at varying storage temperatures (4°C, 10°C, 20°C, and 30°C) and durations before test analysis (1 to 10 days) for 3 I-FOBTs (New Hemtube/Magstream HT, OC-Auto sampling bottle3/OC-Sensor DIANA, and FOB Gold/SENTiFOB). Concentrations ranging from 0 to 350 μg Hb/g of feces were evaluated.

Results: The measurement reproducibility of OC-Sensor was superior to Magstream and far superior to FOB Gold. For all tests, variability was essentially related to sampling. Detected hemoglobin (Hb) levels were substantially lower for all tests at temperatures above 20°C. At 20°C, this loss in concentration was less important with OC-Sensor (significant 1.7% daily decrease vs. 7.4% for Magstream and 7.8% for FOB Gold). At 30°C, daily loss was 8.6% with OC-Sensor, whereas after 24 hours, only 30% of the original Hb was detected with FOB Gold, compared to 70% with Magstream. No Hb was detected on day 5 for the latter 2 tests.

Conclusions: About reproducibility and temperature stability, OC-Sensor performed better than Magstream and far better that FOB Gold.

Impact: Independently of the chosen test, the delay between sampling and test processing should be reduced, the maximal admissible delay depending on ambient temperature. Cancer Epidemiol Biomarkers Prev; 20(7); 1492–501. ©2011 AACR.
Data from Relationship between Epidermal Growth Factor Receptor Status, p16INK4A, and Outcome in Head and Neck Squamous Cell Carcinoma
Authors: Young Richard J. , Rischin Danny , Fisher Richard , McArthur Grant A. , Fox Stephen B. , Peters Lester J. , Corry June , Lim Annette , Waldeck Kelly , Solomon Benjamin
Published: March 2023

Abstract
Background: Human papilloma virus (HPV) infection is a powerful prognostic biomarker in head and neck squamous cell carcinoma (HNSCC). Increased epidermal growth factor receptor (EGFR) gene copy number and protein expression have been reported to be negative predictors of outcome. This study examined the relationship between HPV status, EGFR gene copy number, EGFR protein expression, and clinical outcome in HNSCC patients treated with chemoradiation.

Methods: HPV status was determined using p16INK4A immunohistochemistry (IHC), EGFR gene copy number was evaluated with FISH, and EGFR protein expression by IHC in 212 subjects.

Results:EGFR FISH was positive in 41 of 204 (20%) patients and was negatively correlated with failure-free survival (FFS; HR = 1.84, P = 0.027) and overall survival (OS; HR = 1.78, P = 0.082). For p16INK4A, 85 of 200 (42.5%) patients were found to be p16 positive, including 75 of 131 (57%) with oropharyngeal cancer. Patients with p16-positive oropharyngeal cancer had significantly improved FFS (HR = 0.28, P < 0.001) and OS (HR = 0.31, P = 0.002). Only 2 of 126 (1.6%) oropharyngeal cancer patients were found to be p16+/EGFR FISH+. EGFR IHC was positive in 81 of 93 (87%) of patients and was associated with poorer FFS (HR = 1.98, P = 0.35) and OS (HR = 2.52, P = 0.22).

Conclusions: Increased EGFR gene copy number is largely restricted to p16INK4A-negative oropharyngeal cancer. Although p16INK4A and EGFR FISH are both predictive of outcome in univariate analyses, only p16INK4A remains independently predictive.

Impact: Knowledge of HPV and EGFR status can have implications for treatment options and prognosis in HNSCC. Cancer Epidemiol Biomarkers Prev; 20(6); 1230–7. ©2011 AACR.
Data from Expression of SLCO Transport Genes in Castration-Resistant Prostate Cancer and Impact of Genetic Variation in SLCO1B3 and SLCO2B1 on Prostate Cancer Outcomes
Authors: Wright Jonathan L. , Kwon Erika M. , Ostrander Elaine A. , Montgomery R. Bruce , Lin Daniel W. , Vessella Robert , Stanford Janet L. , Mostaghel Elahe A.
Published: March 2023

Abstract
Background: Metastases from men with castration-resistant prostate cancer (CRPC) harbor increased tumoral androgens versus untreated prostate cancers. This may reflect steroid uptake by OATP (organic anion transporting polypeptide)/SLCO transporters. We evaluated SLCO gene expression in CRPC metastases and determined whether prostate cancer outcomes are associated with single nucleotide polymorphisms (SNP) in SLCO2B1 and SLCO1B3, transporters previously shown to mediate androgen uptake.

Methods: Transcripts encoding eleven SLCO genes were analyzed in untreated prostate cancer and in metastatic CRPC tumors obtained by rapid autopsy. SNPs in SLCO2B1 and SLCO1B3 were genotyped in a population-based cohort of 1,309 Caucasian prostate cancer patients. Median survival follow-up was 7.0 years (0.77–16.4). The risk of prostate cancer recurrence/progression and prostate cancer–specific mortality (PCSM) was estimated with Cox proportional hazards analysis.

Results: Six SLCO genes were highly expressed in CRPC metastases versus untreated prostate cancer, including SLCO1B3 (3.6-fold; P = 0.0517) and SLCO2B1 (5.5-fold; P = 0.0034). Carriers of the variant alleles SLCO2B1 SNP rs12422149 (HR: 1.99; 95% CI: 1.11–3.55) or SLCO1B3 SNP rs4149117 (HR: 1.76; 95% CI: 1.00–3.08) had an increased risk of PCSM.

Conclusions: CRPC metastases show increased expression of SLCO genes versus primary prostate cancer. Genetic variants of SLCO1B3 and SLCO2B1 are associated with PCSM. Expression and genetic variation of SLCO genes which alter androgen uptake may be important in prostate cancer outcomes.

Impact: OATP/SLCO genes may be potential biomarkers for assessing risk of PCSM. Expression and genetic variation in these genes may allow stratification of patients to more aggressive hormonal therapy or earlier incorporation of nonhormonal-based treatment strategies. Cancer Epidemiol Biomarkers Prev; 20(4); 619–27. ©2011 AACR.
Data from A Prospective Cohort Study on Overweight, Smoking, Alcohol Consumption, and Risk of Barrett's Esophagus
Authors: Steevens Jessie , Schouten Leo J. , Driessen Ann L.C. , Huysentruyt Clément J.R. , Keulemans Yolande C.A. , Goldbohm R. Alexandra , van den Brandt Piet A.
Published: March 2023

Abstract
Background: Barrett's esophagus (BE) is a precursor lesion of esophageal adenocarcinoma. Besides gastroesophageal reflux, possible risk factors for BE include overweight, cigarette smoking, and alcohol consumption. Our objective was to study these associations by using prospective data.

Methods: The prospective Netherlands Cohort Study, initiated in 1986, consists of 120,852 men and women, aged 55 to 69 years at baseline. At baseline, all subjects completed a questionnaire on dietary habits and lifestyle. After 16.3 years of follow-up, 370 BE cases with specialized intestinal metaplasia and 3,866 subcohort members were available for case–cohort analysis. Cox proportional hazards models were used to calculate incidence rate ratios (RR) and 95% CIs.

Results: Body mass index (BMI) at baseline was associated with risk of BE in women [multivariable adjusted RR per 1 kg/m2, 1.07 (1.03–1.11)] but not in men [RR per 1 kg/m2, 0.99 (0.93–1.05)]. The association in women was not specifically due to abdominal overweight. Former cigarette smokers were at increased risk of BE (RR = 1.33, 95% CI: 1.00–1.77), but current smokers were not. Smoking duration showed a positive association with BE risk (Ptrend = 0.03). For alcohol consumption, the RR per 10 g ethanol/d was 0.95 (0.87–1.03).

Conclusions: Increased BMI was a risk factor for BE in women but not in men. Several aspects of cigarette smoking were positively associated with BE risk. Alcohol consumption was not associated with an increased risk of BE.

Impact: Future research should focus on risk factors both for development and for progression of BE to esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 20(2); 345–58. ©2010 AACR.
Data from Saliva-Derived DNA Performs Well in Large-Scale, High-Density Single-Nucleotide Polymorphism Microarray Studies
Authors: Bahlo Melanie , Stankovich Jim , Danoy Patrick , Hickey Peter F. , Taylor Bruce V. , Browning Sharon R. , Brown Matthew A. , Rubio Justin P.
Published: March 2023

Abstract
As of June 2009, 361 genome-wide association studies (GWAS) had been referenced by the HuGE database. GWAS require DNA from many thousands of individuals, relying on suitable DNA collections. We recently performed a multiple sclerosis (MS) GWAS where a substantial component of the cases (24%) had DNA derived from saliva. Genotyping was done on the Illumina genotyping platform using the Infinium Hap370CNV DUO microarray. Additionally, we genotyped 10 individuals in duplicate using both saliva- and blood-derived DNA. The performance of blood- versus saliva-derived DNA was compared using genotyping call rate, which reflects both the quantity and quality of genotyping per sample and the “GCScore,” an Illumina genotyping quality score, which is a measure of DNA quality. We also compared genotype calls and GCScores for the 10 sample pairs. Call rates were assessed for each sample individually. For the GWAS samples, we compared data according to source of DNA and center of origin. We observed high concordance in genotyping quality and quantity between the paired samples and minimal loss of quality and quantity of DNA in the saliva samples in the large GWAS sample, with the blood samples showing greater variation between centers of origin. This large data set highlights the usefulness of saliva DNA for genotyping, especially in high-density single-nucleotide polymorphism microarray studies such as GWAS. Cancer Epidemiol Biomarkers Prev; 19(3); 794–8
Data from Validation of a Light Questionnaire with Real-life Photopic Illuminance Measurements: the Harvard Light Exposure Assessment Questionnaire
Authors: Bajaj Archna , Rosner Bernard , Lockley Steven W. , Schernhammer Eva S.
Published: March 2023

Abstract
Background: Shift work, which necessitates light exposure at night, is now considered a probable carcinogen. To study the effects of light on chronic diseases like cancer, methods to measure light exposure in large observational studies are needed. We aimed to investigate the validity of self-reported current light exposure.

Methods: We developed a self-administered semiquantitative light questionnaire, the Harvard Light Exposure Assessment (H-LEA) questionnaire, and compared photopic scores derived from this questionnaire with actual photopic and circadian measures obtained from a real-life 7-day light meter application among 132 women (85 rotating night shift workers and 47 day workers) participating in the Nurses' Health Study II.

Results: After adjustment for age, body mass index (BMI), collection day, and night work status, the overall partial Spearman correlation between self-report of light exposure and actual photopic light measurements was 0.72 (P < 0.001; Kendall τ = 0.57) and 0.73 (P < 0.0001; Kendall τ = 0.58) when correlating circadian light measurements. There were only minimal differences in accuracy of self-report of light exposure and photopic or “circadian” light measurement between day (r = 0.77 and 0.78, respectively) and rotating night shift workers (r = 0.68 and 0.69, respectively).

Conclusions: The results of this study provide evidence of the criterion validity of self-reported light exposure using the H-LEA questionnaire.

Impact: This questionnaire is a practical method of assessing light exposure in large-scale epidemiologic studies. Cancer Epidemiol Biomarkers Prev; 20(7); 1341–9. ©2011 AACR.
Data from Concurrent Infection with Multiple Human Papillomavirus Types: Pooled Analysis of the IARC HPV Prevalence Surveys
Authors: Vaccarella Salvatore , Franceschi Silvia , Snijders Peter J.F. , Herrero Rolando , Meijer Chris J.L.M. , Plummer Martyn
Published: March 2023

Abstract
To understand viral interactions and the cross-reactivity of natural or vaccine-induced responses, we investigated whether multiple human papillomavirus (HPV) infections, particularly certain combinations of types, have the tendency to cluster together. Cervical cell samples were collected from women in the framework of the IARC HPV Prevalence Surveys. Women with a cytology diagnosis of high-grade squamous intraepithelial lesion or worse were excluded, leaving 13,961 women for this analysis. HPV DNA was assessed using a general GP5+/6+ primer–mediated PCR. HPV genotyping was done using enzyme immunoassay or reverse line blot analysis. Logistic regression with type-specific HPV positivity as an outcome was used, adjusted for age, study area, and lifetime number of sexual partners. Woman-level random effects were added to represent unobservable risk factors common to all HPV types. The observed-to-expected ratio was 1.20 (95% credible interval, 1.14-1.26) for infection with two HPV types and 1.02 (95% credible interval, 0.91-1.12) for three for more types, with the best possible adjustment. Among combinations of specific HPV types, the tendency to cluster increased with the genetic similarity of the L1 region. High observed-to-expected ratios were found for closely homologous types, including HPV33/58, 18/45, 33/35, and 31/35. The excess of multiple infections, however, was clearly evident only when enzyme immunoassay, and not reverse line blot, was used as the genotyping method. The different results by genotyping method suggest that the apparent clustering of HPV infections was an artifact of the measurement process. Further investigation is required to evaluate other widely used HPV detection methods. Cancer Epidemiol Biomarkers Prev; 19(2); 503–10
Data from Pooling Prospective Studies to Investigate the Etiology of Second Cancers
Authors: Black Amanda , Gibson Todd M. , Shiels Meredith S. , Park Yikyung , Robien Kim , Albanes Demetrius , Weinstein Stephanie J. , Freeman Laura E. Beane , Andreotti Gabriella , Purdue Mark P. , Fraumeni Joseph F. , Hartge Patricia , Tucker Margaret A. , Hoover Robert N. , Cerhan James R. , Zeleniuch-Jacquotte Anne , Curtis Rochelle E. , Elena Joanne , Sampson Joshua N. , de Gonzalez Amy Berrington , Morton Lindsay M.
Published: March 2023

Abstract
Background: With over 13 million cancer survivors in the United States today, second cancers are of rapidly growing importance. However, data on nontreatment risk factors for second cancers are sparse. We explored the feasibility of pooling data from cohort studies of cancer incidence to investigate second cancer etiology.

Methods: We combined data from five prospective studies including more than 800,000 individuals. We compared study designs and populations; evaluated availability of and ability to harmonize risk factor data; compared incidence and survival for common first primary malignancies and incidence of second primary malignancies; and estimated sample size requirements.

Results: Overall, 96,513 incident, first primary malignancies were diagnosed during 1985 to 2009. Incidence rates and survival following the first primary varied among the cohorts, but most of the heterogeneity could be explained by characteristics of the study populations (age, sex, smoking, and screening rates). A total of 7,890 second primary cancers (excluding original primary site) were identified, yielding sufficient statistical power (≥80%) for detecting modest associations with risk of all second cancers among survivors of common first primary malignancies (e.g., colorectal cancer); however, there were insufficient events for studying survivors of rarer cancers or identifying risk factors for specific second cancers.

Conclusions: Pooling data from cohort studies to investigate nontreatment risk factors for second primary cancers seems feasible but there are important methodologic issues—some of which are barriers to specific research questions—that require special attention.

Impact: Increased understanding of nontreatment risk factors for second cancers will provide valuable prevention and surveillance information. Cancer Epidemiol Biomarkers Prev; 23(8); 1598–608. ©2014 AACR.
Data from Genetic Variation in TYMS in the One-Carbon Transfer Pathway Is Associated with Ovarian Carcinoma Types in the Ovarian Cancer Association Consortium
Authors: Kelemen Linda E. , Goodman Marc T. , McGuire Valerie , Rossing Mary Anne , Webb Penelope M. , Köbel Martin , Anton-Culver Hoda , Beesley Jonathan , Berchuck Andrew , Brar Sony , Carney Michael E. , Chang-Claude Jenny , Chenevix-Trench Georgia , Cramer Daniel W. , Cunningham Julie M. , DiCioccio Richard A. , Doherty Jennifer A. , Easton Douglas F. , Fredericksen Zachary S. , Fridley Brooke L. , Gates Margaret A. , Gayther Simon A. , Gentry-Maharaj Aleksandra , Høgdall Estrid , Kjær Susanne Krüger , Lurie Galina , Menon Usha , Moorman Patricia G. , Moysich Kirsten , Ness Roberta B. , Palmieri Rachel T. , Pearce Celeste L. , Pharoah Paul D.P. , Ramus Susan J. , Song Honglin , Stram Daniel O. , Tworoger Shelley S. , Van Den Berg David , Vierkant Robert A. , Wang-Gohrke Shan , Whittemore Alice S. , Wilkens Lynne R. , Wu Anna H. , Schildkraut Joellen M. , Sellers Thomas A. , Goode Ellen L.
Published: March 2023

Abstract
Background: We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample of assembled cases to investigate associations by histologic type.

Methods: Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and study site.

Results: The five polymorphisms were not associated with ovarian carcinoma overall (Ptrend > 0.13); however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; Pheterogeneity = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05).

Conclusions: TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification.

Impact: Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology. Cancer Epidemiol Biomarkers Prev; 19(7); 1822–30. ©2010 AACR.
Data from Smoking at Diagnosis Is an Independent Prognostic Factor for Cancer-Specific Survival in Head and Neck Cancer: Findings from a Large, Population-Based Study
Authors: Sharp Linda , McDevitt Joseph , Carsin Anne-Elie , Brown Christopher , Comber Harry
Published: March 2023

Abstract
Background: Some studies suggest smoking may result in poorer clinical outcomes in head and neck cancer, but the evidence is heterogeneous and some of it is poor quality. In a large, population-based, study we investigated: (i) whether smoking at diagnosis is an independent prognostic factor for cancer-specific survival in head and neck cancer; and (ii) whether the association varies by site and treatment.

Methods: Head and neck cancers (ICD10 C01-C14, and C30–32) diagnosed from 1994 to 2009 were abstracted from the National Cancer Registry Ireland, and classified by smoking status at diagnosis. Follow-up was for 5 years or until December 31, 2010. Multivariate Cox proportional hazards models were used to compare cancer-specific death rates in current, ex-, and never smokers. Subgroup analyses by site and treatment were conducted.

Results: In total, 5,652 head and neck cancers were included. At diagnosis, 24% were never smokers, 20% ex-smokers, and 56% current smokers. Compared with never smokers, current smokers had a significantly raised death rate from cancer [multivariate HR, 1.36; 95% confidence interval (CI), 1.21–1.53]. The association was similar after restriction to squamous cell tumors. A significantly increased cancer-related death rate was seen for current smokers with oral cavity, pharyngeal, and laryngeal cancers. The association was stronger in surgically treated patients [HR, 1.49; 95% CI, 1.25–1.79; P(interaction) = 0.01]. Neither radiotherapy nor chemotherapy modified the effect of smoking.

Conclusions: Patients with head and neck cancer who smoke at diagnosis have a significantly increased cancer death rate.

Impact: Greater efforts are needed to encourage and support smoking cessation in those at risk of, and diagnosed with, head and neck cancer. Cancer Epidemiol Biomarkers Prev; 23(11); 2579–90. ©2014 AACR.
Data from Menopausal Hormone Therapy and Subsequent Risk of Specific Invasive Breast Cancer Subtypes in the California Teachers Study
Authors: Saxena Tanmai , Lee Eunjung , Henderson Katherine D. , Clarke Christina A. , West Dee , Marshall Sarah F. , Deapen Dennis , Bernstein Leslie , Ursin Giske
Published: March 2023

Abstract
Background: Although it is well established that combined estrogen-progestin therapy (EPT) increases breast cancer risk, questions remain regarding the effect of different formulations of hormones, whether certain women are at particularly high risk, and whether risk varies by tumor subtype.

Methods: We investigated hormone therapy (HT) use in relation to breast cancer risk in the California Teachers Study cohort; after a mean follow-up of 9.8 years, 2,857 invasive breast cancers were diagnosed.

Results: Compared with women who had never used HT, women who reported 15 or more years of estrogen therapy (ET) use had a 19% greater risk of breast cancer (95% confidence interval, 1.03-1.37), whereas women using EPT for 15 or more years had an 83% greater risk (95% confidence interval, 1.48-2.26). Breast cancer risk was highest among women using continuous combined EPT regimens. Risks associated with EPT and ET use were increased with duration of HT use for women with a body mass index (BMI) of <29.9 kg/m2 but not for women with BMI of ≥30 kg/m2. Elevated risks associated with EPT and ET use were confined to tumors that were positive for both estrogen and progesterone receptors and those that were HER2+ but were slightly diminished for HER2− tumors.

Conclusions: Breast cancer risks increased with longer duration of ET and EPT use, and risks were highest for continuous-combined EPT use. Furthermore, risks varied by BMI and tumor subtype.

Impact: These findings underscore the need for personalized risk-benefit discussions with women contemplating HT use. Cancer Epidemiol Biomarkers Prev; 19(9); 2366–78. ©2010 AACR.
Data from Fetal Growth, Preterm Birth, Neonatal Stress and Risk for CNS Tumors in Children: A Nordic Population- and Register-Based Case-Control Study
Authors: Schmidt Lisbeth Samsø , Schüz Joachim , Lähteenmäki Päivi , Träger Catarina , Stokland Tore , Gustafson Göran , Hjalgrim Lisa , Sehested Astrid , Johansen Christoffer , Schmiegelow Kjeld
Published: March 2023

Abstract
Background: The peak incidence of central nervous system (CNS) tumors in childhood indicates that intrauterine or neonatal characteristics are potential risk factors or symptoms of early onset of disease.

Methods: We conducted a registry-based case-control study nested in the childhood populations of Denmark, Finland, Sweden, and Norway on the association between indicators of fetal growth and neonatal stress and childhood CNS tumor risk diagnosed during the period 1985-2006. Each of the 3,443 cases was matched individually on date of birth, sex, and country to five controls sampled randomly from population registries. Information on birth characteristics was obtained from national birth registries. We estimated odds ratios (OR) and 95% confidence intervals (95% CI) by conditional logistic regression analyses.

Results: We observed a U-shaped relation between risk for CNS tumors and birthweight, at >4.5 kg (OR, 1.27; 95% CI, 1.03-1.55) and <2.0 kg (OR, 1.50; 95% CI, 1.13-1.99), the latter being attenuated after adjustment for gestational age. Moreover, small-for-gestational age (OR, 1.28; 95% CI, 0.98-1.66) and large-for-gestational age (OR, 1.26; 95% CI, 1.02-1.55) were both associated with CNS tumors. The OR for preterm births was increased per 1-week decrease in gestational age (OR, 1.58; 95% CI, 1.04-2.44). Increased ORs were also observed for head circumference >38 cm (1.80; 95% CI, 1.18-2.74), 5-minute Apgar score <7 (1.44; 95% CI, 0.98-2.12), and breech presentation (1.33; 95% CI, 1.04-1.69). The observed associations varied little by histologic subgroup.

Conclusions: This study supports intrauterine or neonatal onset of childhood CNS tumors. The findings provide insight into the natural history of childhood CNS tumors indicating an early onset or, alternatively, potentially harmful exposures in the neonatal period that might be preventable. Cancer Epidemiol Biomarkers Prev; 19(4); 1042–52. ©2010 AACR.
Data from The Effect of Exercise Training on Mediators of Inflammation in Breast Cancer Survivors: A Systematic Review with Meta-analysis
Authors: Meneses-Echávez Jose F. , Correa-Bautista Jorge E. , González-Jiménez Emilio , Schmidt Río-Valle Jacqueline , Elkins Mark R. , Lobelo Felipe , Ramírez-Vélez Robinson
Published: March 2023

Abstract
Several sources of evidence indicate that exercise during and after breast cancer could positively modulate the tumor microenvironment. This meta-analysis aimed to determine the effects of exercise training on mediators of inflammation in breast cancer survivors. We searched for randomized controlled trials published from January 1990 to March 2014. An inverse variance method of meta-analysis was performed using a random effects model in the presence of statistical heterogeneity. Eight high-quality trials (n = 478) were included. Exercise improved the serum concentrations of IL6 [weighted mean difference (WMD) = −0.55 pg/mL; 95% confidence interval (CI), −1.02 to −0.09], TNFα (WMD = −0.64 pg/mL; 95% CI, −1.21 to −0.06), IL8 (MD = −0.49 pg/mL; 95% CI, −0.89 to −0.09), and IL2 (WMD = 1.03 pg/mL; 95% CI, 0.40 to 1.67). No significant differences were found in the serum concentrations of C-reactive protein (WMD = −0.15; 95% CI, −0.56 to 0.25) or IL10 (WMD = 0.41; 95% CI, −0.18 to 1.02). Exercise training positively modulates chronic low-grade inflammation in women with breast cancer, which may impact upon carcinogenic mechanisms and the tumor microenvironment. These findings align with the other positive effects of exercise for breast cancer survivors, reinforcing the appropriateness of exercise prescription in this population. Cancer Epidemiol Biomarkers Prev; 25(7); 1009–17. ©2016 AACR.