bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary Sucrose and Fructose as Biomarkers for Sugar Consumption
Authors: Tasevska Natasa , Runswick Shirley A. , McTaggart Alison , Bingham Sheila A.
Published: September 2005

The use of 24-hour urinary sucrose and fructose as potential biomarkers for sugars consumption was investigated in two studies of 21 healthy participants living in a volunteer suite where dietary intake was known and all specimens collected. The dose-response was assessed in 12 males using a randomized crossover design of three diets containing constant levels of 63, 143, and 264 g of sugars for 10 days each. Both sugars and sucrose intake were significantly correlated with the sum of sucrose and fructose concentration in urine (0.888; P < 0.001). To assess effects with volunteers consuming their habitual varying diets, seven males and six females were fed their usual diet (assessed beforehand from four consecutive self-completed 7-day food diaries) for 30 days under controlled conditions in the volunteer suite. The mean (±SD) calculated total sugars intake was 202 ± 69 g/d, 41% from sucrose. Mean (±SD) urinary sucrose and fructose were 36.6 ± 16.6 and 61.8 ± 61.3 mg/d, respectively. The sum of sucrose and fructose in urine was significantly correlated with sugars (0.841; P < 0.001) and sucrose intake (0.773; P = 0.002). In the regression, 200 g of sugars intake predicted ∼100 mg of sucrose and fructose in urine. The correlation between individual means of randomized 16 days of sugars intake and 8 days of sugars excretion data (as used in validation studies) remained as high as that obtained with the means of 30-day measurements and the regression estimates were very similar. Twenty-four–hour urinary sucrose and fructose could be grouped into a new category of biomarkers, predictive biomarkers, that can be used in studies determining the structure of dietary measurement error in free living individuals and to relate sugars intake to disease risk.
Spectral Markers in Preneoplastic Intestinal Mucosa: An Accurate Predictor of Tumor Risk in the MIN Mouse
Authors: Roy Hemant K. , Kim Young L. , Wali Ramesh K. , Liu Yang , Koetsier Jennifer , Kunte Dhananjay P. , Goldberg Michael J. , Backman Vadim
Published: September 2005

Background: We have reported recently that microarchitectural analysis of the histologically normal mucosa using a novel optics technology, four-dimensional elastic light scattering fingerprinting (ELF), provided unprecedented sensitivity for early detection of colon carcinogenesis. In the present study, we explored the ability of four-dimensional ELF to identify an inherited predisposition to colorectal cancer, an issue of considerable importance for optimizing population screening strategies.

Methods: We used the MIN mouse, a model whose germ line adenomatous polyposis coli truncation leads to spontaneous intestinal tumorigenesis, thus replicating the human syndrome, familial adenomatous polyposis. Spectral markers were assessed by four-dimensional ELF analysis in MIN mice at preneoplastic time points and compared with age-matched controls (C57BL6 mice with wild-type adenomatous polyposis coli). To assess the responsiveness of spectral markers to chemopreventive agents, a subset of MIN mice was supplemented with celecoxib 1,500 ppm.

Results: Spectral slope, fractal dimension, and principal component 3 were dramatically altered in the uninvolved MIN mouse mucosa at the earliest time points. Furthermore, alteration in spectral variables increased over time, consonant with the microarchitectural underpinnings of subsequent tumorigenesis. Additionally, these markers spatially correlated with future adenoma development (small intestine > colon). Short-term treatment with the potent chemopreventive agent, celecoxib, resulted in near normalization of fractal dimension and principal component 3.

Conclusions: We report, for the first time, that spectral markers, assayed by four-dimensional ELF, were able to sensitively identify a genetic predisposition for intestinal tumorigenesis before the occurrence of phenotypic manifestations. Moreover, the reversal of spectral markers by celecoxib treatment supports the neoplastic relevance.
Associations between Plasma Insulin-Like Growth Factor Proteins and C-Peptide and Quality of Life in Patients with Metastatic Colorectal Cancer
Authors: Meyerhardt Jeffrey A. , Sloan Jeffrey A. , Sargent Daniel J. , Goldberg Richard M. , Pollak Michael , Morton Roscoe F. , Ramanathan Ramesh K. , Williamson Stephen K. , Findlay Brian P. , Fuchs Charles S.
Published: September 2005

Objective: Predictors of quality of life (QOL) in patients with metastatic colorectal cancer are lacking. The insulin-like growth factor (IGF) family of proteins is associated with QOL in noncancer populations. We sought to study whether these proteins are associated with QOL in patients with colorectal cancer.

Method: We used a cohort of 526 patients with metastatic colorectal cancer treated with combination chemotherapy. Plasma samples of IGF-I, IGF-II, IGF binding protein-3, and C-peptide were collected before initiation of chemotherapy. QOL was measured by the uniscale instrument and the Symptom Distress Scale at baseline and throughout treatment.

Results: Baseline plasma levels of IGF-I and IGF-II before initiation of chemotherapy were significantly associated with several important baseline QOL measures in patients with metastatic colorectal cancer. Patients with lower levels of IGF-I reported increased distress with regard to appearance, appetite, cough, and nausea intensity after adjustment for potential confounders. Similarly, decreased levels of IGF-II were predictive of worse quality related to appearance, appetite, fatigue, nausea frequency and intensity, pain frequency, and composite Symptom Distress Scale score. IGF binding protein-3 and C-peptide were not predictive of baseline QOL. Baseline biomarkers were not associated with subsequent changes in QOL during treatment. Higher body mass index was significantly associated with superior baseline QOL in several areas; nonetheless, the association of IGF-I and IGF-II with baseline QOL measures remained significant even after controlling for baseline body mass index.

Conclusion: Baseline plasma IGF-I and IGF-II are significantly associated with symptom distress. Whether this association is simply reflective of patient nutritional status and/or disease burden or represents an independent biological effect of IGFs on QOL remains uncertain. Nonetheless, these data suggest that molecular biomarkers may be useful predictors of QOL in cancer patients.
Is the Association with Fiber from Foods in Colorectal Cancer Confounded by Folate Intake?
Authors: Bingham Sheila A. , Norat Teresa , Moskal Aurelie , Ferrari Pietro , Slimani Nadia , Clavel-Chapelon Françoise , Kesse Emmanuelle , Nieters Alexandra , Boeing Heiner , Tjønneland Anne , Overvad Kim , Martinez Carmen , Dorronsoro Miren , González Carlos A. , Ardanaz Eva , Navarro Carmen , Quirós José R. , Key Timothy J. , Day Nicholas E. , Trichopoulou Antonia , Naska Androniki , Krogh Vittorio , Tumino Rosario , Palli Domenico , Panico Salvatore , Vineis Paolo , Bueno-de-Mesquita H.B. , Ocké Marga C. , Peeters Petra H.M. , Berglund Göran , Hallmans Göran , Lund Eiliv , Skeie Guri , Kaaks Rudolf , Riboli Elio
Published: September 2005

The effect of multivariate adjustment including folate on the strong protective effect of fiber in foods on colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition was investigated in 1,721 cases identified in the latest follow-up. The inclusion of an additional 656 cases confirmed our previously published results, with a strong and significant reduction in colorectal cancer risk of ∼9% for each uncalibrated quintile increase in fiber (Plinear trend < 0.001) compared with an 8% reduction in our previous report, which had not been adjusted for folate. Inclusion of the other covariates (physical activity, alcohol, smoking, and red and processed meat) confirmed this significant inverse association for colon cancer and strengthened the association with left-sided colon cancer (P < 0.001). After maximum adjustment, the association between fiber and rectal cancer was not significant, as in our previous analysis. The association with fiber from different food sources was analyzed, but again, there were no significance trends after maximum adjustment.
A Molecular Epidemiology Case Control Study on Pleural Malignant Mesothelioma
Authors: Bolognesi Claudia , Martini Fernanda , Tognon Mauro , Filiberti Rosa , Neri Monica , Perrone Emanuela , Landini Eleonora , Canessa Paolo A. , Ivaldi Gian Paolo , Betta Pietro , Mutti Luciano , Puntoni Riccardo
Published: September 2005

Pleural malignant mesothelioma is an uncommon neoplasm usually associated with asbestos exposure. The increasing incidence of malignant mesothelioma cases involving individuals with low levels of asbestos exposure suggests a complex carcinogenetic process with the involvement of other cofactors. Cytogenetic studies revealed the complexity of the genetic changes involved in this neoplasm reflecting the accumulation of genomic damage. One of the most used methodologies for assessing genomic damage is the cytokinesis-blocked micronucleus test applied in peripheral blood lymphocytes (PBL). This approach allows the detection of chromosomal alterations expressed in binucleated cells after nuclear division in vitro. This marker could provide a tool for assessing genetically determined constitutional differences in chromosomal instability. A biomonitoring study was carried out to evaluate the micronuclei frequency in PBLs of patients with pleural malignant mesothelioma with respect to lung cancer, healthy, and risk controls as a marker of cancer susceptibility in correlation with the presence of SV40. A significant increased micronuclei frequency was observed in patients with malignant mesothelioma in comparison with all the other groups, the mean micronuclei frequency was double in patients with malignant mesothelioma compared with healthy controls, risk controls, and patients with lung adenocarcinoma (median 11.4 binucleated cells with micronuclei/1,000 binucleated cells versus 6.2, 6.1, and 5.1, respectively). Our data indicate that human T lymphocyte samples carry DNA sequences coding for SV40 large T antigen at low prevalence, both in cancer cases and controls. Evidence of cytogenetic damage revealed as micronuclei frequency in mesothelioma cancer patients could be related to exogenous and endogenous cofactors besides asbestos exposure.
Total Cholesterol and Body Mass Index in Relation to 40-Year Cancer Mortality (The Corfu Cohort of the Seven Countries Study)
Authors: Panagiotakos Demosthenes B. , Pitsavos Christos , Polychronopoulos Evangelos , Chrysohoou Christina , Menotti Alessandro , Dontas Anastasios , Stefanadis Christodoulos
Published: September 2005

Purpose: We evaluated risk factors of cancer mortality based on a 40-year follow-up of the Corfu cohort (Seven Countries Study).

Material and Methods: The population studied in this analysis consisted of 529 rural men (49 ± 6 years old) enrolled in 1961. Since then, periodic visits every 5 years were made to define the causes of death of the participants. Cox proportional hazards models evaluated various risk factors in relation to cancer mortality.

Results: The death rate at the end of the follow-up was 87.1% (i.e., 461 deaths in 529 participants). Of those deaths, 118 (25.6%) were because of cancer (30 deaths were due to cancer of trachea, bronchus, and lung, and the rest were due to other malignant neoplasms). Cancer was the second cause of death in this cohort, after coronary heart disease. Age (hazard ratio, 1.05 per year; P < 0.05), smoking (hazard ratio, 1.97; P < 0.01), total serum cholesterol levels (hazard ratio, 0.95 per 10 mg/dL; P < 0.05), and body mass index (hazard ratio, 0.93 per 1 kg/m2; P < 0.05) showed a significant association with cancer deaths after controlling for physical activity status and anthropometric indices. It should be noted that the protective effect of total cholesterol on cancer mortality was observed only between 183 and 218 mg/dL baseline levels.

Conclusion: Cancer was one of the leading causes of death in this cohort. Smoking was associated with increased risk of cancer, whereas moderate total serum cholesterol and increased body and mass index seemed to have a protective effect on 40-year cancer mortality.
Association of Vegetable Intake with Urinary 6-Sulfatoxymelatonin Level
Authors: Nagata Chisato , Nagao Yasuko , Shibuya Chiken , Kashiki Yoshitomo , Shimizu Hiroyuki
Published: September 2005

Melatonin is present in plants consumed as vegetables; however, only a limited number of vegetables have been tested for melatonin. The antiproliferative, antioxidative, and immunostimulatory effects of melatonin have been reported from laboratory studies. The potential protective effects of vegetable against cancer and cardiovascular disease may be partially attributable to an increased melatonin intake from vegetables. As a first step to test this hypothesis, we evaluated whether vegetable intake is associated with an increased urinary melatonin in 289 community-dwelling Japanese women. Diet, including vegetable consumption, was assessed with a validated 169-item semiquantitative food-frequency questionnaire. Urinary 6-sulfatoxymelatonin (aMT6-s) was measured in the first-void morning urines. There was a significant positive association between vegetable intake and urinary aMT6-s levels. The mean urinary aMT6-s was 16% higher in women with the highest quartile of vegetable intake than it was in those with the lowest quartile of intake. This association may be explained by the melatonin contained in vegetables. However, data should be regarded as preliminary because it is impossible to estimate dietary melatonin intake from vegetables and or from the entire diet because of incomplete data for melatonin in plants.
Role of Dietary Factors in the Development of Basal Cell Cancer and Squamous Cell Cancer of the Skin
Authors: McNaughton Sarah A. , Marks Geoffrey C. , Green Adele C.
Published: September 2005

The role of dietary factors in the development of skin cancer has been investigated for many years; however, the results of epidemiologic studies have not been systematically reviewed. This article reviews human studies of basal cell cancer (BCC) and squamous cell cancer (SCC) and includes all studies identified in the published scientific literature investigating dietary exposure to fats, retinol, carotenoids, vitamin E, vitamin C, and selenium. A total of 26 studies were critically reviewed according to study design and quality of the epidemiologic evidence. Overall, the evidence suggests a positive relationship between fat intake and BCC and SCC, an inconsistent association for retinol, and little relation between β-carotene and BCC or SCC development. There is insufficient evidence on which to make a judgment about an association of other carotenoids with skin cancer. The evidence for associations between vitamin E, vitamin C, and selenium and both BCC and SCC is weak. Many of the existing studies contain limitations, however, and further well-designed and implemented studies are required to clarify the role of diet in skin cancer. Additionally, the role of other dietary factors, such as flavonoids and other polyphenols, which have been implicated in skin cancer development in animal models, needs to be investigated.
Obesity and Outcomes in Premenopausal and Postmenopausal Breast Cancer
Authors: Loi Sherene , Milne Roger L. , Friedlander Michael L. , McCredie Margaret R.E. , Giles Graham G. , Hopper John L. , Phillips Kelly-Anne
Published: September 2005

Purpose: Obesity is associated with adverse outcomes in postmenopausal women with breast cancer. In premenopausal women, the association is less clear.

Methods: A population-based sample of 1,360 Australian women with breast cancer before the age of 60 years, 47% diagnosed before age 40, and 74% premenopausal, was studied prospectively for a median of 5 years (range, 0.2-10.8 years). Obesity was defined as a body mass index of ≥30 kg/m2. The hazard ratio (HR) for adverse clinical outcome associated with obesity was estimated using Cox proportional hazard survival models.

Results: Obesity increased with age (P < 0.001) and was associated with increased breast cancer recurrence (P = 0.02) and death (P = 0.06), larger tumors (P = 0.002), and more involved axillary nodes (P = 0.003) but not with hormone receptor status (P ≥ 0.6) or with first cycle adjuvant chemotherapy dose reductions (P = 0.1). Adjusting for number of axillary nodes, age at diagnosis, tumor size, grade, and hormone receptor status, obese women of all ages were more likely than nonobese women to have disease recurrence [HR, 1.57; 95% confidence interval (95% CI), 1.11-2.22; P = 0.02] and to die from any cause during follow-up (HR, 1.56; 95% CI, 1.01-2.40; P = 0.05). In premenopausal women, the adjusted HRs were 1.50 (95% CI, 1.00-2.26; P = 0.06) and 1.71 (95% CI, 1.05-2.77; P = 0.04), respectively.

Conclusions: Obesity is independently associated with poorer outcomes in premenopausal women, as it is in postmenopausal women, and this is not entirely explained by differences in tumor size or nodal status. Given the high and increasing prevalence of obesity in western countries, more research on improving the treatment of obese breast cancer patients is warranted.
Genetic Polymorphisms of the Transforming Growth Factor-β1 Gene and Breast Cancer Risk: A Possible Dual Role at Different Cancer Stages
Authors: Shin Aesun , Shu Xiao-Ou , Cai Qiuyin , Gao Yu-Tang , Zheng Wei
Published: September 2005

Transforming growth factor-β (TGF-β) inhibits the proliferation of carcinomas in early stages of breast cancer, whereas it promotes tumor growth and metastasis in later stages of cancer. We evaluated a possible association between TGF-β1 gene polymorphisms and breast cancer risk in a population-based case-control study of Chinese women living in Shanghai, which included 1,127 breast cancer cases and 1,228 population controls. Two polymorphisms, C-509T and T+29C, were in strong linkage disequilibrium. There were no overall differences in the genotype distribution of T+29C polymorphisms of the TGF-β1 gene among cases and controls. However, the distribution of the high-activity C allele of T+29C polymorphisms differed by cancer stages (Ptrend = 0.02). This allele was associated with decreased risk of early-stage breast cancer [stages 0 and I; odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.54-0.99], and the OR was further reduced to 0.66 (95% CI, 0.45-0.96) for those homozygous for this allele (Ptrend = 0.03). On the other hand, the same allele was associated with nonsignificantly increased risk of breast cancer with advanced stages III and IV (OR, 1.33; 95% CI, 0.81-2.18), which differed significantly from that observed for early-stage cancer (P = 0.04). This result suggests a possible dual effect of TGF-β1 shown by in vitro experiments and provides an explanation for some of the inconsistent findings from previous epidemiologic studies that did not evaluate this association by cancer stage.
Maternal Diet and Acute Lymphoblastic Leukemia in Young Children
Authors: Petridou Eleni , Ntouvelis Evangelos , Dessypris Nick , Terzidis Agapios , Trichopoulos Dimitrios ,   the Childhood Hematology-Oncology Group
Published: September 2005

Because leukemia clone-specific chromosomal abnormalities are present at birth in children who later develop leukemia, it has been hypothesized that maternal factors, including nutrition during pregnancy, might affect the risk of acute lymphoblastic leukemia (ALL) among young children. We have evaluated this hypothesis in a nationwide case-control study of ALL among children ages 12 to 59 months in Greece. Children (n = 131) with ALL were gender and age matched to control children (n = 131) hospitalized for minor conditions between 1999 and 2003. The mothers of the children were interviewed in person by trained interviewers who used an extensive food frequency questionnaire addressing diet during the index pregnancy. The analysis was done by modeling the data through conditional logistic regression, also controlling for total energy intake and possible confounding factors. Odds ratios (OR) and 95% confidence intervals (95% CI) were expressed per quintile increase of maternal intake during pregnancy of the specified food group. The risk of ALL in the offspring was lower with increased maternal intake of fruits (OR, 0.72; 95% CI, 0.57-0.91), vegetables (OR, 0.76; 95% CI, 0.60-0.95), and fish and seafood (OR, 0.72; 95% CI, 0.59-0.89) and higher with increased maternal intake of sugars and syrups (OR, 1.32; 95% CI, 1.05-1.67) and meat and meat products (OR, 1.25; 95% CI, 1.00-1.57). Children of women who tend to consume during their pregnancies what is currently considered to be a healthy diet maybe at lower risk of ALL.
Intestinal Helminthiasis in Colombian Children Promotes a Th2 Response to Helicobacter pylori: Possible Implications for Gastric Carcinogenesis
Authors: Whary Mark T. , Sundina Nataliya , Bravo Luis E. , Correa Pelayo , Quinones Francisco , Caro Fanny , Fox James G.
Published: September 2005

Background: Colombians living in coastal Tumaco have a lower incidence of Helicobacter pylori–associated gastric cancer compared with residents of Pasto in the high Andes. Considering the risk for H. pylori disease seems affected by features of bacterial virulence and host polymorphisms, other poorly understood influences, such as concurrent helminthiasis, may also be important.

Methods: Fecal samples from 211 children were tested for parasites and sera from another cohort of 159 children and 92 adults were tested for IgE and H. pylori–specific IgG.

Results: Most individuals (95%) from both areas were H. pylori seropositive, with a predominant response of IgG1 followed by IgG2 and low IgG3 and IgG4 antibodies. Compared with Pasto children, Tumaco children were more commonly infected with helminths (P = 0.000), had higher serum IgE levels (P < 0.03), and had higher Th2-associated IgG1 responses to H. pylori (P < 0.0002). Other IgG isotype responses all increased with age but were not significantly different between children and adults from either area.

Conclusions: These results suggest that intestinal helminthiasis in children promotes Th2-polarizing responses to H. pylori and may decrease gastric cancer risk in these individuals later in life. Concurrent helminthiasis may alter inflammatory responses to H. pylori and thus affect the progression of gastritis to gastric atrophy, dysplasia, and cancer.
Expression of Nucleotide Excision Repair Proteins in Lymphocytes as a Marker of Susceptibility to Squamous Cell Carcinomas of the Head and Neck
Authors: Wei Qingyi , Wang Li-E , Sturgis Erich M. , Mao Li
Published: September 2005

The transcript levels of nucleotide excision repair (NER) genes were shown to be associated with risk of squamous cell carcinomas of the head and neck (SCCHN). However, this association may be biased, because the transcript level does not necessarily reflect the level of protein expression. To address this issue, we did a pilot study to test the hypothesis that the expression of six core NER proteins is associated with risk of SCCHN. We obtained cultured lymphocytes from 57 patients with newly diagnosed SCCHN patients and 63 cancer-free controls. We transfected some of the lymphocytes with both damaged and undamaged plasmid DNA and quantified NER protein levels in these lymphocytes using a reverse-phase protein microarray. The relative NER protein levels in the 63 controls were highly correlated with each other (P < 0.001 for all). Compared with the controls, the cases had lower expression levels for all the NER proteins, particularly XPC and XPF, which were reduced by about 25% (P < 0.01). When we used the median expression levels of the NER proteins in the controls as cutoff values, we found that a significantly increased risk of SCCHN was associated with low expression of XPA [odds ratio (OR), 2.99; 95% confidence interval (CI), 1.22-7.47], XPC (OR, 2.46; 95% CI, 1.04-5.87), XPD (OR, 3.02; 95% CI, 1.18-7.76), and XPF (OR, 5.29; 95% CI, 2.01-13.9), but not ERCC1 and XPG, after adjustment for age, sex, ethnicity, smoking, alcohol use, and sample storage time. In a multivariate logistic regression model that included all covariates and NER proteins, however, only low expression of XPF remained a significant risk factor for SCCHN (OR, 11.5; 95% CI, 2.32-56.6). These results suggest that XPF may be a crucial rate-limiting factor in DNA repair and that the reverse-protein microarray assay may be a useful tool for measuring protein markers of susceptibility to cancer.
Further Enhanced Monitoring of Cancer Patient Survival by Stage-Adjusted Period Analysis
Authors: Brenner Hermann , Arndt Volker
Published: September 2005

Monitoring progress in cancer patient survival is an important task of population-based cancer registration. Period analysis has been shown to provide more up-to-date estimates of cancer patient survival than traditional methods of survival analysis. However, even period estimates may disclose recent improvements in long-term survival with some delay as they are still partly based on the survival experience of patients diagnosed years ago. If these patients had a less favorable stage distribution than the patients diagnosed in a more recent calendar period (e.g., due to progress in early detection), period estimates may underestimate long-term survival for patients diagnosed in that period. This particular source of potential underestimation can be overcome by adjustment of the stage distribution of all patients included in period analysis to the stage distribution of the patients diagnosed in the period of interest. The principle, application, and use of stage adjustment of period survival estimates are illustrated with 5- and 10-year relative survival estimates of patients diagnosed with breast cancer and followed with respect to survival in the United States between 1973 and 2001, using data of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. We show that stage adjustment may often further enhance the benefits of period analysis for deriving up-to-date cancer survival estimates.
Plasma Levels of Enterolactone and Percentage Mammographic Density among Postmenopausal Women
Authors: Stuedal Anne , Gram Inger Torhild , Bremnes Yngve , Adlercreutz Herman , Veierød Marit B. , Ursin Giske
Published: September 2005

Aims: Certain phytoestrogens, such as lignans, may protect against developing breast cancer. Enterolactone is a lignan metabolite produced by the intestinal flora from dietary precursors such as whole grains, vegetables, and fruits. Enterolactone has been shown to have weak estrogenic and antiestrogenic properties. We decided to examine the association between plasma levels of enterolactone and mammographic density, a biomarker for breast cancer risk.

Methods: We included data from postmenopausal women ages 55 and older who participated in a cross-sectional mammogram study in Tromsø, Norway. Mammograms, plasma enterolactone measurements, as well as information on anthropometric and hormonal/reproduction factors were available on 616 women. We assessed mammographic density using a previously validated computer-assisted method. We estimated correlation coefficients and conducted multiple regression analyses.

Results: Mean mammographic density increased slightly across quartiles of enterolactone; the women in the highest quartile had, on average, 3.1% (absolute difference) higher percentage mammographic density compared with the lowest quartile (Ptrend < 0.01). After adjustment for age, body mass index, number of full-term pregnancies, age at first birth, and use of postmenopausal hormone therapy, the mean difference in density was reduced to 2.0% (Ptrend = 0.05). Results were similar when restricted to the 454 current hormone nonusers. The fully adjusted statistical model explained 28.3% of the total variability in mammographic percentage density, with body mass index contributing 18.2% and enterolactone only 0.9%.

Conclusion: In our study, higher levels of enterolactone were associated with slightly higher percentage mammographic density. Our results suggest that if higher enterolactone levels reduce the risk of developing breast cancer in postmenopausal women, then this effect is not through lowering mammographic density.
A Phase I Study of Indole-3-Carbinol in Women: Tolerability and Effects
Authors: Reed Gregory A. , Peterson Kirstin S. , Smith Holly J. , Gray John C. , Sullivan Debra K. , Mayo Matthew S. , Crowell James A. , Hurwitz Aryeh
Published: September 2005

We completed a phase I trial of indole-3-carbinol (I3C) in 17 women (1 postmenopausal and 16 premenopausal) from a high-risk breast cancer cohort. After a 4-week placebo run-in period, subjects ingested 400 mg I3C daily for 4 weeks followed by a 4-week period of 800 mg I3C daily. These chronic doses were tolerated well by all subjects. Hormonal variables were measured near the end of the placebo and dosing periods, including determination of the urinary 2-hydroxyestrone/16α-hydroxyestrone ratio. Measurements were made during the follicular phase for premenopausal women. Serum estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone binding globulin showed no significant changes in response to I3C. Caffeine was used to probe for cytochrome P450 1A2 (CYP1A2), N-acetyltransferase-2 (NAT-2), and xanthine oxidase. Comparing the results from the placebo and the 800 mg daily dose period, CYP1A2 was elevated by I3C in 94% of the subjects, with a mean increase of 4.1-fold. In subjects with high NAT-2 activities, these were decreased to 11% by I3C administration but not altered if NAT-2 activity was initially low. Xanthine oxidase was not affected. Lymphocyte glutathione S-transferase activity was increased by 69% in response to I3C. The apparent induction of CYP1A2 was mirrored by a 66% increase in the urinary 2-hydroxyestrone/16α-hydroxyestrone ratio in response to I3C. The maximal increase was observed with the 400 mg daily dose of I3C, with no further increase found at 800 mg daily. If the ratio of hydroxylated estrone metabolites is a biomarker for chemoprevention, as suggested, then 400 mg I3C daily will elicit a maximal protective effect.
Positive and Negative Associations of Human Leukocyte Antigen Variants with the Onset and Prognosis of Adult Glioblastoma Multiforme
Authors: Tang Jianming , Shao Wenshuo , Dorak M. Tevfik , Li Yufeng , Miike Rei , Lobashevsky Elena , Wiencke John K. , Wrensch Margaret , Kaslow Richard A. , Cobbs Charles S.
Published: September 2005

Associations of genetic factors with malignant gliomas have been modest. We examined the relationships of human leukocyte antigen (HLA) and related polymorphisms to glioblastoma multiforme in adult Caucasians (non–Hispanic Whites) from the San Francisco Bay area. For 155 glioblastoma multiforme patients and 157 control subjects closely matched by ethnicity, age, and gender, PCR-based techniques resolved alleles at HLA-A, -B, -C, and -DRB1 loci along with short tandem repeat polymorphisms of MICA exon 5 and TNFb. By multivariable logistic regression, B*13 and the B*07-Cw*07 haplotype were positively associated with glioblastoma multiforme (P = 0.01 and <0.001, respectively), whereas Cw*01 was the only variant showing a negative association (P = 0.05). Among glioblastoma multiforme patients, progression to death after diagnosis was slower in those with A*32 (relative hazard, 0.45; P < 0.01) and faster in those with B*55 (relative hazard, 2.27; P < 0.01). Thus, both the occurrence and the prognosis of glioblastoma multiforme could be associated with specific but different HLA genotypes. B*07 and the B*07-Cw*07 haplotype are much more common in Caucasians than other ethnic groups in the U.S., which may partially explain the higher incidence of glioblastoma multiforme in Caucasians.
Socioeconomic Factors and Risk of Esophageal Adenocarcinoma: A Nationwide Swedish Case-Control Study
Authors: Jansson Catarina , Johansson Anna L.V. , Nyrén Olof , Lagergren Jesper
Published: September 2005

Background: The increase in esophageal adenocarcinoma incidence in developed countries remains unexplained. Although low socioeconomic status (SES) is linked to an increased risk of esophageal squamous cell carcinoma (SCC), the relation with adenocarcinoma is uncertain.

Methods: We addressed the importance of various socioeconomic factors in a Swedish population-based case-control study, where 189 and 262 cases of esophageal adenocarcinoma and the gastric cardia, respectively, 167 cases of esophageal SCC, and 820 control participants underwent personal interviews. Our classification of SES was derived from occupational histories. Relative risks were estimated by odds ratios with 95% confidence intervals (95% CI), derived from conditional logistic regression, in crude and adjusted models.

Results: The risk of both esophageal adenocarcinoma and SCC increased with decreasing SES; unskilled workers had 3.7-fold (95% CI, 1.7-7.7) and 2.1-fold (95% CI, 1.0-4.7) increased risks, respectively, compared with age- and sex-comparable professionals. Adjustment for reflux symptoms, body mass, and tobacco smoking attenuated the excess risk for esophageal adenocarcinoma, whereas adjustment for Helicobacter pylori infection in a subset of the interviewed participants did not influence the results. Life without a partner was associated with a >2-fold increased risk of both histologic types of esophageal cancer, associations that remained even after multiple adjustments.

Conclusions: Esophageal adenocarcinoma and SCC are both linked to low SES and a life without a partner. These associations are only partly explained by established risk factors.
Role of Androgen Metabolism Genes CYP1B1, PSA/KLK3, and CYP11α in Prostate Cancer Risk and Aggressiveness
Authors: Cicek Mine S. , Liu Xin , Casey Graham , Witte John S.
Published: September 2005

Candidate genes involved with androgen metabolism have been hypothesized to affect the risk of prostate cancer. To further investigate this, we evaluated the relationship between prostate cancer and multiple potentially functional polymorphisms in three genes involved in androgen metabolism: CYP1B1 (two single nucleotide polymorphisms: 355G/T and 4326C/G), prostate-specific antigen (PSA/KLK3 (three single nucleotide polymorphisms: −158A/G, −4643G/A, and −5412C/T), and CYP11α [(tttta)n repeat], using a moderately large (n = 918) sibling-based case-control population. When looking at all subjects combined, no association was observed between any polymorphism—or their haplotypes—and prostate cancer risk. However, among men with more aggressive prostate cancer, the CYP1B1 355G/T variant was positively associated with disease: carrying one or two T alleles gave odds ratios (OR) of 1.90 [95% confidence interval (95% CI), 1.09-3.31; P = 0.02] and 3.73 (95% CI, 1.39-10.0; P = 0.009), respectively. Similarly, carrying the CYP1B1 355T-4326C haplotype was positively associated with prostate cancer among men with high aggressive disease (P = 0.01). In addition, the PSA −158G/−158G genotype was positively associated with prostate cancer among men with less aggressive disease (OR, 2.71; 95% CI, 1.06-6.94; P = 0.04). Our findings suggest that CYP1B1 and PSA variants may affect the risk of prostate cancer and tumor aggressiveness.
Is There Overlap Between the Genetic Determinants of Mammographic Density and Bone Mineral Density?
Authors: Dite Gillian S. , Wark John D. , Giles Graham G. , English Dallas R. , McCredie Margaret R.E. , Hopper John L.
Published: September 2005

Mammographic density and bone mineral density, risk factors for breast cancer and osteoporotic fractures, respectively, are both thought to reflect cumulative exposure to estrogen and are highly heritable. We asked if there was overlap between the genes that explain their variances. We studied 63 monozygous and 71 dizygous female twin pairs ages 38 to 71 years (mean, 50 years). Absolute and percent mammographic densities were measured by a computer-assisted method, and bone mineral density was measured at the lumbar spine, femoral neck, and forearm by dual energy X-ray absorptiometry. After adjusting for age, height, and weight, the within-person and cross-trait cross-twin correlations between the mammographic density and bone mineral density measures were between −0.09 and 0.16 (SEs, 0.07-0.09) and independent of zygosity (all P > 0.05). We conclude that there is little, if any, overlap between the genetic or environmental determinants of disease risk associated with these traits.
A Prospective Study of the Insulin-Like Growth Factor Axis in Relation with Prostate Cancer in the SU.VI.MAX Trial
Authors: Meyer François , Galan Pilar , Douville Pierre , Bairati Isabelle , Kegle Pastelle , Bertrais Sandrine , Czernichow Sébastien , Hercberg Serge
Published: September 2005

Several epidemiologic studies have examined with diverging results the relationships between circulating levels of insulin-like growth factors (IGF) and of IGF-binding proteins (IGFBP) and prostate cancer risk. We assessed the association of prediagnostic plasma levels of IGF-I, IGF-II, IGFBP-2, and IGFBP-3 and subsequent occurrence of prostate cancer in a case-control study nested in the SU.VI.MAX trial. The SU.VI.MAX study was a primary prevention trial testing a daily supplementation with low-dose antioxidant vitamins and minerals in male and female middle-aged volunteers in France. One hundred prostate cancer cases were diagnosed among 4,855 SU.VI.MAX participants over a 9-year follow-up period. For each case, four age-matched controls were selected randomly. Frozen baseline plasma samples were used to measure IGF-I, IGF-II, IGFBP-2, and IGFBP-3. Conditional logistic regression was used to assess the association between these four biochemical markers and prostate cancer risk. After controlling for the intervention group in the trial and the other IGF axis variables, the odds ratios and 95% confidence interval (95% CI) comparing the upper quartile to the baseline quartile were 1.83 (95% CI, 0.85-3.95), 1.05 (95% CI, 0.35-3.18), 0.79 (95% CI, 0.39-1.58), and 0.42 (95% CI, 0.12-1.52) for IGF-I, IGF-II, IGFBP-2, and IGFBP-3, respectively. More suggestive associations for IGF-I and IGFBP-3 were observed with advanced and aggressive cancers. Our results are consistent with those of some previous prospective studies and suggest that IGF axis variables are not long-term predictors of the occurrence of prostate cancer.
WHO Non-Hodgkin's Lymphoma Classification by Criterion-Based Report Review followed by Targeted Pathology Review: An Effective Strategy for Epidemiology Studies
Authors: Turner Jennifer J. , Hughes Ann Maree , Kricker Anne , Milliken Sam , Grulich Andrew , Kaldor John , Armstrong Bruce
Published: September 2005

In a previous criterion-based pathology report review of 717 cases of non-Hodgkin's lymphoma in an Australian population-based epidemiologic study, a WHO category could be assigned in 91% of cases, but confidence in this classification was high in only 57.5%. Given this lack of confidence, a pathology review was done in a subset of 315 cases, with the aims of assigning a WHO classification category and the corresponding International Classification of Diseases for Oncology, Third Edition code in all cases previously unclassified or classified with low confidence and testing the accuracy of report review in assigning a confident WHO classification. After pathology review, 10 cases were ineligible (not non-Hodgkin's lymphoma, 3.2%) and 99% (301 of 305) of the remainder were assigned a WHO classification, with high confidence in 87% (261 of 301). There was 78% overall agreement between the WHO classification assigned by report review and pathology review, with 92% agreement when there was high confidence in the report review classification and 69% agreement when there was low confidence. Eighteen percent of follicular lymphomas and 23% of diffuse large B-cell lymphomas were reclassified. The pathology review increased the accuracy of WHO classification by an estimated 12.5% in the 694 cases who were still eligible in the study. Although a potential error rate of 7.5% remained, reviewing more cases, or not reviewing any cases classified with high confidence, would have produced only a small change in accuracy. Criterion-based pathology report review of all cases followed by selective pathology review in cases classified with low confidence is recommended as a cost-saving and accurate strategy for pathology review in large epidemiologic studies.
Current Research Promises and Challenges in Behavioral Oncology
Authors: Miller Suzanne M. , Bowen Deborah J. , Campbell Marci K. , Diefenbach Michael A. , Gritz Ellen R. , Jacobsen Paul B. , Stefanek Michael , Fang Carolyn Y. , Lazovich DeAnn , Sherman Kerry A. , Wang Catharine
Published: September 2005

The Behavioral Oncology Interest Group of the American Society of Preventive Oncology held a Roundtable session on March 10, 2002, at the American Society of Preventive Oncology annual meeting in Bethesda, Maryland, to discuss the current state-of-the-science in behavioral approaches to cancer prevention and control and to delineate priorities for additional research. Four key areas were considered: (a) behavioral approaches to cancer genetic risk assessment and testing; (b) biological mechanisms of psychosocial effects on cancer; (c) the role of risk perceptions in cancer screening adherence; and (d) the impact of tailored and targeted interventions on cancer prevention and control research. The evidence reviewed indicates that behavioral approaches have made significant contributions to cancer prevention and control research. At the same time, there is a need to more closely link future investigations to the underlying base of behavioral science principles and paradigms that guide them. To successfully bridge the gap between the availability of effective new cancer prevention and control technologies and the participants they are meant to serve will require the development of more integrative conceptual models, the incorporation of more rigorous methodological designs, and more precise identification of the individual and group characteristics of the groups under study.
Prevalence of Colorectal Cancer Screening in a Large Medical Organization
Authors: Hawley Sarah T. , Vernon Sally W. , Levin Bernard , Vallejo Beryl
Published: September 2005

The primary objective of this study was to determine the prevalence of colorectal cancer (CRC) screening among eligible patients in a large medical practice. A secondary objective was to compare CRC screening rates obtained from medical records with physician self-reported CRC screening recommendation. We conducted a retrospective record review of 214 patients ages ≥ 50 years of a large multispecialty medical organization in Houston, Texas, for receipt of fecal occult blood test (FOBT), flexible sigmoidoscopy (SIG), and/or colonoscopy (COL). We estimated prevalence using two definitions: (a) FOBT in past year or SIG in past 5 years or COL in past 10 years; and (b) FOBT in past year and SIG in past 5 years or COL in past 10 years. Age, gender, race/ethnicity, family history, number of chronic conditions, and index visit were independent variables. Contingency table and logistic regression analysis were used to test for associations between outcomes and independent variables. Our study population was 48% male with a mean age of 63 years (range: 53–84 years). One-quarter of the records showed FOBT by 3-day kit (51 of 214) and 27% by digital rectal exam (57 of 214). SIG was recorded in 32% of records. Half (54%) of the records had documentation of CRC screening according to definition no. 1 and 19% according to definition no. 2. Screening rates from medical record review were lower than those derived from physician self-report. Our findings underscore the need for interventions to improve CRC screening in primary care settings.
Cisplatin Sensitizes Cancer Cells to Ionizing Radiation via Inhibition of Nonhomologous End Joining
Authors: Boeckman Heather J. , Trego Kelly S. , Turchi John J.
Published: September 2005

The combination of cisplatin and ionizing radiation (IR) treatment represents a common modality for treating a variety of cancers. These two agents provide considerable synergy during treatment, although the mechanism of this synergy remains largely undefined. We have investigated the mechanism of cisplatin sensitization to IR using a combination of in vitro and in vivo experiments. A clear synergistic interaction between cisplatin and IR is observed in cells proficient in nonhomologous end joining (NHEJ) catalyzed repair of DNA double-strand breaks (DSB). In contrast, no interaction between cisplatin and IR is observed in NHEJ-deficient cells. Reconstituted in vitro NHEJ assays revealed that a site-specific cisplatin-DNA lesion near the terminus results in complete abrogation of NHEJ catalyzed repair of the DSB. These data show that the cisplatin-IR synergistic interaction requires the DNA-dependent protein kinase–dependent NHEJ pathway for joining of DNA DSBs, and the presence of a cisplatin lesion on the DNA blocks this pathway. In the absence of a functional NHEJ pathway, although the cells are hypersensitive to IR, there is no synergistic interaction with cisplatin.
Discovery of Epigenetically Masked Tumor Suppressor Genes in Endometrial Cancer
Authors: Takai Noriyuki , Kawamata Norihiko , Walsh Christine S. , Gery Sigal , Desmond Julian C. , Whittaker Sadie , Said Jonathan W. , Popoviciu Laura M. , Jones Peter A. , Miyakawa Isao , Koeffler H. Phillip
Published: September 2005

Realization that many tumor suppressor genes are silenced by epigenetic mechanisms has stimulated the discovery of novel tumor suppressor genes. We used a variety of research tools to search for genes that are epigenetically silenced in human endometrial cancers. Changes in global gene expression of the endometrial cancer cell line Ishikawa was analyzed after treatment with the demethylating agent 5-aza-2′-deoxycytidine combined with the histone deacetylase inhibitor suberoylanilide bishydroxamide. By screening over 22,000 genes, candidate tumor suppressor genes were identified. Additional microarray analysis and real-time reverse transcription-PCR of normal and cancerous endometrial samples and search for CpG islands further refined the list. Tazarotene-induced gene-1 (Tig1) and CCAAT/enhancer binding protein-α (C/ebpα) were chosen for further study. Expression of both genes was low in endometrial cancer cell lines and clinical samples but high in normal endometrial tissues. Bisulfite sequencing, restriction analysis, and/or methylation-specific PCR revealed aberrant methylation of the CpG island in the Tig1 gene of all 6 endometrial cancer cell lines examined and 4 of 18 clinical endometrial cancers, whereas the C/ebpα promoter remained unmethylated in endometrial cancers. Chromatin immunoprecipitation showed increased acetylated histone H3 bound to both Tig1 and C/ebpα genes after treatment with 5-aza-2′-deoxycytidine and/or suberoylanilide bishydroxamide. Forced expression of either TIG1 or C/EBPα led to significant growth reduction of Ishikawa cells. Our data suggest that C/ebpα and Tig1 function as tumor suppressor proteins in endometrial cancers and that their reexpression may be a therapeutic target.