bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cutting Cost and Increasing Access to Colorectal Cancer Screening: Another Approach to Following the Guidelines
Authors: Fisher Judith A. , Fikry Christopher , Troxel Andrea B. 
Published: March 2006

Abstract
Context: Through medical decision making, physicians in the U.S. influence the spending of &gt;$1.3 trillion or 15% of the gross domestic product. U.S. physicians are challenged to identify areas of clinical practice to improve while cutting cost and increasing access. Primary screening for colorectal cancer is a good example to illustrate this point.
Objective: To apply a population-based method of medical decision making in the area of primary screening for colorectal cancer in order to illustrate a reduction in health care costs while increasing access and maintaining quality of care.
Design: We used a combination of (a) census population data, (b) National Cancer Institute Survey data on screening rates, and (c) charge data to estimate the current costs of colorectal cancer screening. We also estimated cost and capacity increases that would occur under various other screening scenarios. These included all currently screened subjects receiving annual fecal occult blood testing (FOBT), all currently unscreened individuals undergoing either colonoscopy every decade or annual FOBT, and all eligible subjects undergoing annual FOBT.
Main outcome measures: Cost and access differences between current screening activity and other potential scenarios compliant with guidelines.
Results: Screening for colorectal cancer with yearly, six-window, rehydrated FOBT for all normal-risk individuals over the age of 50 has the potential to screen 3,813,095 more Americans for colon cancer yearly than are currently being screened, while costing $8.7 billion less per decade than what is currently being spent on screening a fraction of the population. Looking into the future, it is possible to increase screening rates from 50% to 100%, while saving almost $10 billion per decade by using FOBT for all eligible Americans. In practice, some proportion of these benefits would be realized as the calculations assume a 100% patient compliance rate.
Conclusions: Considering a population-based approach and the balance among quality, accessibility, and cost parameters, we recommend primary screening for colorectal cancer to be based on yearly six-window, rehydrated FOBT. Colonoscopy due to cost and access issues should be relegated to secondary screening and case finding. (Cancer Epidemiol Biomarkers Prev 2006;15(1):108–13)
Factorial Validity and Invariance of a Survey Measuring Psychosocial Correlates of Colorectal Cancer Screening among African Americans and Caucasians
Authors: Tiro Jasmin A. , Vernon Sally W. , Hyslop Terry , Myers Ronald E. 
Published: March 2006

Abstract
Background: Psychosocial constructs are widely used to predict colorectal cancer screening and are targeted as intermediate outcomes in behavioral intervention studies. Reliable and valid instruments for measuring general colorectal cancer screening psychosocial constructs are needed; yet, few studies have conducted psychometric analyses. This study replicated a five-factor structure for 16 theory-based, general colorectal cancer screening items measuring salience and coherence, cancer worries, perceived susceptibility, response efficacy, and social influence. In addition, we examined factorial invariance across race and sex.
Methods: African American and Caucasian patients (n = 1,413) attending an urban, primary care clinic were included in this study. These individuals completed a baseline survey as part of a colorectal cancer screening intervention trial. Single and multigroup confirmatory factor analyses using maximum-likelihood estimation were done.
Results: The five-factor general colorectal cancer screening model provided excellent fit and was invariant across race-sex subgroups.
Conclusions: The findings of invariance across sex and race subgroups support the use of these scales to measure group differences. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2855-61)
Smoking, The Missing Drug Interaction in Clinical Trials: Ignoring the Obvious
Authors: Gritz Ellen R. , Dresler Carolyn , Sarna Linda 
Published: March 2006

AbstractTobacco use is universally recognized as the foremost preventable cause of cancer in the United States and globally and is responsible for 30% of all cancer-related deaths in the United States. Tobacco use, including exposure to secondhand smoke has been implicated as a causal or contributory agent in an ever-expanding list of cancers, including lung, oral cavity and pharynx, pancreas, liver, kidney, ureter, urinary bladder, uterine cervix, and myeloid leukemia. In addition to and independent of the etiologic effects of tobacco carcinogens in numerous cancers, there is a growing literature on the direct and indirect effects of smoking on treatment efficacy (short-term and long-term outcomes), toxicity and morbidity, quality of life (QOL), recurrence, second primary tumors (SPT), and survival time as summarized below. Oncology health professionals have called for increased advocacy for tobacco control. Despite the critical relevance of smoking to cancer outcomes, most oncology clinical trials do not collect data on smoking history and status unless the malignancy is widely acknowledged as smoking related (e.g., lung or head and neck cancer). Usually, these data are collected only at trial registration. Changes in smoking status during treatment or follow-up are monitored in very few trials and are infrequently reported in sample descriptions or included in analysis plans as a potential moderator of outcomes. Based on mounting evidence that tobacco use affects cancer treatment outcomes and survival, we recommend that smoking history and status be systematically collected as core data in all oncology clinical trials: at diagnosis, at trial registration, and throughout treatment and follow-up to long-term survival or death. We feel that the inclusion and analysis of such data in clinical trials will add important information to the interpretation of outcomes and the development of scientific knowledge in this area. Smoking status has been called another “vital sign” because of its relevance to a patient's immediate medical condition. We explain the critical value of knowing the smoking status of every patient with cancer at every visit by providing a brief overview of the following research findings: (a) the effects of tobacco use on cancer treatment and outcome; (b) recent findings on the role of nicotine in malignant processes; (c) some unexpected results concerning tobacco status, treatment, and disease outcome; and (d) identifying key questions that remain to be addressed. We provide a suggested set of items for inclusion in clinical trial data sets that also are useful in clinical practice.
Association of Polymorphisms in ERCC2 Gene with Non-Familial Thyroid Cancer Risk
Authors: Silva Susana N. , Gil Octávia Monteiro , Oliveira Vanessa C. , Cabral Marisa N. , Azevedo Ana Paula , Faber Ana , Manita Isabel , Ferreira Teresa Cruz , Limbert Edward , Pina Julieta Esperança , Rueff José , Gaspar Jorge 
Published: March 2006

Abstract
The ERCC2 protein is an evolutionary conserved ATP-dependent helicase that is associated with a TFIIH transcription factor complex and plays an important role in nucleotide excision repair. Mutations in this gene are responsible for xeroderma pigmentosum and also for Cocayne syndrome and trichothiodystrophy. Several single nucleotide polymorphisms have been identified in the ERCC2 locus. Among them, a G23591A polymorphism in the codon 312 results in an Asp → Asn substitution in a conserved region and a A35931C polymorphism in the codon 751 results in a Lys → Gln substitution. Because these polymorphisms have been associated with an increased risk for several types of cancers, we carried out an hospital based case-control study in a Caucasian Portuguese population to evaluate the potential role of these polymorphisms on the individual susceptibility to thyroid cancer. The results obtained did not reveal a significant association between each individual polymorphism studied (G23591A and A35931C) and an increased thyroid cancer risk, but individuals homozygous for non-wild-type variants are overrepresented in patients group. The evaluation of the different haplotypes generated by these polymorphisms showed that individuals simultaneously homozygous for rare variants of both polymorphisms have an increased risk for thyroid cancer [adjusted odds ratio (OR) 3.084; 95% confidence interval (95% CI), 1.347-7.061; P = 0.008] and for papillary thyroid–type tumors (adjusted OR, 2.997; 95% CI, 1.235-7.272; P = 0.015) but not for follicular thyroid–type tumors. These results suggest that genetic polymorphisms in this gene might be associated with individual susceptibility towards thyroid cancer, mainly papillary-type tumors, but larger studies are required to confirm these results.
Association between Quantitative High-Risk Human Papillomavirus DNA Load and Cervical Intraepithelial Neoplasm Risk
Authors: Tsai Hsiu-Ting , Wu Ching-Hu , Lai Hsiao-Ling , Li Ruei-Nian , Tung Yi-Ching , Chuang Hung-Yi , Wu Trong-Neng , Lin Li-Jen , Ho Chi-Kung , Liu Hon-Wein , Wu Ming-Tsang 
Published: March 2006

Abstract
Human papillomavirus (HPV) infection is a high-risk factor for cervical intraepithelial neoplasm (CIN) but the association between the quantitative HPV DNA load and the severity of CIN remains controversial. We conducted a community study to investigate the correlation between the two. Potential study subjects were selected through Pap smear screening in Kaohsiung County, Taiwan. Ninety-one subjects with either their first case of inflammation or ≥CIN1 by biopsy confirmation were assigned to a case group; 175 normal subjects with negative findings by Pap smears or biopsies were assigned to a control group. Cervical HPV load was detected with Hybrid Capture II assay for high-risk HPV infection, with nested PCR for high- and low-risk HPV infection, and with type-specific PCR for HPV type 16 (HPV-16). Individuals with positive high-risk HPV infection had an increased risk of developing CIN. Compared with HPV-negative subjects, the odds ratios were 32.2 [95% confidence interval (95% CI), 10.4-99.5] for subjects with CIN1, 37.2 (95% CI, 7.4-187.6) for subjects with CIN2, and 68.3 (95% CI, 14.1-328.5) for subjects with ≥CIN3 after adjusting for other confounding factors. The similar trend was also found among the HPV-16–negative individuals. In addition, high-risk HPV DNA load levels were highly correlated with the different grades of CINs in the overall population (Spearman's correlation coefficient r = 0.67, P &lt; 0.0001, n = 266) and the HPV-16–negative population (Spearman's correlation coefficient r = 0.58, P &lt; 0.0001, n = 234). We concluded that high-risk HPV infection, irrespective of HPV-16 infection, was highly and positively associated with the development of CIN.
Genetic Mechanisms of TP53 Loss of Heterozygosity in Barrett's Esophagus: Implications for Biomarker Validation
Authors: Wongsurawat V. Jon , Finley Jennifer C. , Galipeau Patricia C. , Sanchez Carissa A. , Maley Carlo C. , Li Xiaohong , Blount Patricia L. , Odze Robert D. , Rabinovitch Peter S. , Reid Brian J. 
Published: March 2006

AbstractBackground and Aims: 17p (TP53) loss of heterozygosity (LOH) has been reported to be predictive of progression from Barrett's esophagus to esophageal adenocarcinoma, but the mechanism by which TP53 LOH develops is unknown. It could be (a) DNA deletion, (b) LOH without copy number change, or (c) tetraploidy followed by genetic loss. If an alternative biomarker assay, such as fluorescence in situ hybridization (FISH), provided equivalent results, then translation to the clinic might be accelerated, because LOH genotyping is presently limited to research centers.Methods: We evaluated mechanisms of TP53 LOH to determine if FISH and TP53 LOH provided equivalent results on the same flow-sorted samples (n = 43) representing established stages of clonal progression (diploid, diploid with TP53 LOH, aneuploid) in 19 esophagectomy specimens.Results: LOH developed by all three mechanisms: 32% had DNA deletions, 32% had no copy number change, and 37% had FISH patterns consistent with a tetraploid intermediate followed by genetic loss. Thus, FISH and LOH are not equivalent (P &lt; 0.000001).Conclusions: LOH develops by multiple chromosome mechanisms in Barrett's esophagus, all of which can be detected by genotyping. FISH cannot detect LOH without copy number change, and dual-probe FISH is required to detect the complex genetic changes associated with a tetraploid intermediate. Alternative biomarker assay development should be guided by appreciation and evaluation of the biological mechanisms generating the biomarker abnormality to detect potential sources of discordance. FISH will require validation in adequately powered longitudinal studies before implementation as a clinical diagnostic for esophageal adenocarcinoma risk prediction. (Cancer Epidemiol Biomarkers Prev 2006;15(3):509–16)
Preventive Health Behaviors and Familial Breast Cancer
Authors: Madlensky Lisa , Vierkant Robert A. , Vachon Celine M. , Pankratz V. Shane , Cerhan James R. , Vadaparampil Susan Thomas , Sellers Thomas A. 
Published: March 2006

Abstract
Aim: To examine medical and lifestyle preventive behaviors among women with varying levels of familial breast cancer risk.
Methods: Using cross-sectional data from the Minnesota Breast Cancer Family Study, a historical cohort of 426 families, we compared medical (mammography adherence, antiestrogen use, and prophylactic surgery) and lifestyle (physical activity, smoking, alcohol, and diet) behaviors across three groups of cancer-free women ages 18 to 95 defined by their family history of breast cancer. Family history was classified as high-risk, moderate-risk, or average to low-risk depending on the number and degree of relationship of family members with breast cancer.
Results: After adjusting for age and education, high-risk women were twice as likely to have ever used an antiestrogenic agent (9.0% versus 4.6% among moderate-risk and 4.1% among average to low-risk; P = 0.002). Among women ages &lt;40, the high-risk group were more likely to have ever had a mammogram (82% versus 47% among moderate-risk and 35% among average to low-risk; P &lt; 0.001). Average to low-risk women were the least likely to be current smokers and high-risk women may consume slightly fewer fruits and vegetables compared with the other groups, but there were no other differences in lifestyle behaviors, including physical activity and alcohol use.
Conclusions: Women with strong family histories of breast cancer are more likely to undertake medical but not lifestyle preventive behaviors.
Polymorphisms in the Reduced Folate Carrier, Thymidylate Synthase, or Methionine Synthase and Risk of Colon Cancer
Authors: Ulrich Cornelia M. , Curtin Karen , Potter John D. , Bigler Jeannette , Caan Bette , Slattery Martha L. 
Published: March 2006

AbstractFolate metabolism supports the synthesis of nucleotides as well as the transfer of methyl groups. Polymorphisms in folate-metabolizing enzymes have been shown to affect risk of colorectal neoplasia and other malignancies. Using data from a population-based incident case-control study (1,600 cases and 1,962 controls), we investigated associations between genetic variants in the reduced folate carrier (RFC), thymidylate synthase (TS), methionine synthase (MTR), and 5,10-methylenetetrahydrofolate reductase (MTHFR) and colon cancer risk. The TS enhancer region (TSER) variant was associated with a reduced risk among men [2rpt/2rpt versus 3rpt/3rpt wild-type; odds ratio (OR), 0.7; 95% confidence interval, 0.6-0.98] but not women. When combined genotypes for both TS polymorphisms (TSER and 3′-untranslated region 1494delTTAAAG) were evaluated, ORs for variant genotypes were generally below 1.0, with statistically significantly reduced risks among women. Neither MTR D919G nor RFC 80G&gt;A polymorphisms were associated with altered colon cancer risk. Because folate metabolism is characterized by interrelated reactions, we evaluated gene-gene interactions. Genotypes resulting in reduced MTHFR activity in conjunction with low TS expression were associated with a reduced risk of colon cancer. When dietary intakes were taken into account, individuals with at least one variant TSER allele (3rpt/2rpt or 2rpt/2rpt) were at reduced risk in the presence of a low folate intake. This study supports findings from adenoma studies indicating that purine synthesis may be a relevant biological mechanism linking folate metabolism to colon cancer risk. A pathway-based approach to data analysis is needed to help discern the independent and combined effects of dietary intakes and genetic variability in folate metabolism.
DNA Repair Polymorphisms and Risk of Colorectal Adenomatous or Hyperplastic Polyps
Authors: Bigler Jeannette , Ulrich Cornelia M. , Kawashima Toana , Whitton John , Potter John D. 
Published: March 2006

AbstractGenetic variability in DNA repair genes may contribute to differences in DNA repair capacity and susceptibility to cancer, especially in the presence of exposures such as smoking. In a Minnesota-based case-control study of cases with only adenomatous polyps (n = 384), only hyperplastic polyps (n = 191), or both types of polyps (n = 119) versus polyp-free controls (n = 601), we investigated the role of polymorphisms in the DNA repair genes O6-methylguanine methyltransferase (MGMT; p.L84F and p.I143V), XPD (p.D312N and p.K751Q), and XPG (p.D1104H). MGMT polymorphisms were not associated with polyp risk. Overall, a homozygous variant XPD–combined genotype was associated with an increased risk of adenomatous polyps [odds ratio (OR), 1.57; 95% confidence interval (95% CI), 1.04-2.38] and an XPGHH1104 genotype with a decreased risk of hyperplastic polyps (OR, 0.36; 95% CI, 0.13-0.98). However, age stratification showed that the XPD association was present only in subjects ≥60 years old (OR, 3.77; 95% CI, 1.94-7.35), whereas the XPG association was observed largely in subjects &lt;60 years old (OR, 0.20; 95% CI, 0.05-0.91). Smokers did not have a significantly increased risk of adenomatous polyps in the absence of synchronous hyperplastic polyps, except for subjects with a homozygous variant XPD genotype or a homozygous wild-type XPG genotype (OR, 3.93; 95% CI, 1.68-9.21 and OR, 1.59; 95% CI, 1.01-2.50, respectively). Smoking was associated with a statistically significant 2.5- to 6-fold increased risk of hyperplastic polyps for individuals with most of the DNA repair genotypes. However, no substantial increase was observed among individuals who were homozygous variant for XPG (1104HH; OR, 1.38; 95% CI, 0.25-7.65). Our data suggest that polymorphisms in DNA repair genes may be risk factors for colorectal neoplasia and that they may exacerbate the effects of exposures to carcinogens.
Associations Between Polymorphisms in the Vitamin D Receptor and Breast Cancer Risk
Authors: Chen Wendy Y. , Bertone-Johnson Elizabeth R. , Hunter David J. , Willett Walter C. , Hankinson Susan E. 
Published: March 2006

AbstractBiological and epidemiologic data suggest that vitamin D levels may influence breast cancer development. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D and additionally interacts with other cell-signaling pathways that influence cancer development. Because functional data exist on FOK1 and previous studies have suggested a relation between BSM1 and breast cancer risk, we evaluated the associations of the FOK1 and BSM1 VDR polymorphisms and breast cancer risk. In a case-control study nested within the Nurses' Health Study, we genotyped 1,234 incident cases (diagnosed between return of a blood sample in 1989-1990 and June 1, 2000) and 1,676 controls for FOK1, and 1,180 cases and 1,547 controls for BSM1. We observed a significantly increased risk of breast cancer among carriers of the ff genotype of FOK1 (multivariate odds ratio, 1.34; 95% confidence intervals, 1.06-1.69) compared with those with FF. We did not observe an association between polymorphisms in BSM1 and breast cancer risk (multivariate odds ratio, 0.93; 95% confidence intervals, 0.72-1.20) for BB versus bb). The FOK1 association did not vary significantly by menopausal status, estrogen, and progesterone receptor status of the tumors, or plasma levels of 25 hydroxyvitamin D or 1,25 dihydroxyvitamin D. Our results suggest that the VDR may be a mediator of breast cancer risk and could represent a target for cancer prevention efforts.
Genetic Polymorphisms of Flavin Monooxygenase 3 in Sulindac-Induced Regression of Colorectal Adenomas in Familial Adenomatous Polyposis
Authors: Hisamuddin Irfan M. , Wehbi Mohammad A. , Schmotzer Brian , Easley Kirk A. , Hylind Linda M. , Giardiello Francis M. , Yang Vincent W. 
Published: March 2006

Abstract
Sulindac is a nonsteroidal antiinflammatory drug with a chemopreventive effect in patients with familial adenomatous polyposis (FAP). In vivo, the active form of sulindac is sulindac sulfide, which is inactivated by the hepatic microsomal enzyme, flavin monooxygenase 3 (FMO3). In humans, numerous polymorphisms exist in FMO3, which alter enzymatic activity and subsequent substrate metabolism. We recently showed that certain polymorphic forms of FMO3 with reduced activity were associated with a more favorable response to sulindac in preventing the formation of adenomas in patients with FAP without polyps at baseline. Here, we determined whether these FMO3 polymorphisms correlated with the ability of sulindac to regress polyposis in patients with FAP who had polyps prior to treatment. Nineteen patients were treated with 150 mg sulindac twice a day for 6 months. The size and number of polyps in each patient was assessed at baseline (prior to the administration of sulindac), and at 3 and 6 months. Genotyping was done on seven established FMO3 polymorphisms with functional significance—M66I, E158K, P153L, V257M, E305X, E308G, and R492W. Statistical analyses were done with Wilcoxon rank sum test. Of the loci examined, only E158K and E308G showed polymorphic changes. Six patients exhibited polymorphisms in both E158K and E308G loci and were designated as genotype combination 1. The remaining patients were designated as genotype combination 2. Over the course of treatment, patients with genotype combination 1 had a greater reduction in both the size and number of polyps than those with genotype combination 2. These results suggest that combined polymorphic changes in the E158K and E308G alleles may protect against polyposis in patients with FAP treated with sulindac.