bluuebunny/crossref_metadata_2025 huggingface dataset:
Project PREVENT: A Randomized Trial to Reduce Multiple Behavioral Risk Factors for Colon Cancer
Authors: Emmons Karen M. , McBride Colleen M. , Puleo Elaine , Pollak Kathryn I. , Clipp Elizabeth , Kuntz Karen , Marcus Bess H. , Napolitano Melissa , Onken Jane , Farraye Frank , Fletcher Robert
Published: September 2005

Background: This report examines the outcome data for Project PREVENT, a two-site randomized control trial designed to reduce behavioral risk factors for colorectal cancer among individuals who have been diagnosed with adenomatous colon polyps.

Methods: The study sample included 1,247 patients with recent diagnosis of adenomatous colorectal polyps. Within 4 weeks following the polypectomy, participants completed a baseline survey by telephone, and were randomized to either Usual Care (UC) or the PREVENT intervention, which was designed to target multiple risk factors. The intervention consisted of a telephone-delivered intervention plus tailored materials, and focused on the six primary behavioral risk factors for colorectal cancer, including red meat consumption, fruit and vegetable intake, multivitamin intake, alcohol, smoking, and physical inactivity.

Results: Participation in the PREVENT intervention was associated with a significantly greater reduction in prevalence of multiple risk factors for colorectal cancer compared with UC. Only about one third of UC participants dropped any risk factors during the study period, compared with almost half of the PREVENT participants. PREVENT participants were also significantly more likely to change more than one behavior than UC participants.

Conclusions: The PREVENT intervention was effective in helping patients change multiple risk factors. These results provide further support that more comprehensive interventions that move beyond emphasis on a single risk factor are acceptable to patient populations, can result in improvements, and are cost effective.
Tumor Antigen Markers for the Detection of Solid Cancers in Inflammatory Myopathies
Authors: Amoura Zahir , Duhaut Pierre , Huong Du Le Thi , Wechsler Bertrand , Costedoat-Chalumeau Nathalie , Francès Camille , Cacoub Patrice , Papo Thomas , Cormont Sylvie , Touitou Yvan , Grenier Philippe , Valeyre Dominique , Piette Jean-Charles
Published: September 2005

Dermatomyositis and polymyositis patients have an increased risk of developing cancers. We have assessed the diagnostic values of serum tumor markers for the detection of solid cancer in dermatomyositis/polymyositis patients. Serum carcinoembryonic antigen, CA15-3, CA19-9, and CA125 were assayed by immunoradiometric methods in 102 dermatomyositis/polymyositis patients. All the patients had complete physical examination, chest X-ray, echocardiogram, gastrointestinal tract endoscopic explorations, thoracoabdomino-pelvic computed tomography scan, and all women had gynecologic examination and mammogram. Exclusion criteria for study were childhood dermatomyositis, inclusion body myositis, myositis associated with a connective tissue disease, prior history of cancer, and the presence of benign conditions known to elevate serum tumor markers. After a median follow-up of 59 months, 10 (9.8%) patients had a solid cancer. Initial elevation of CA125 was associated with an increased risk of developing solid cancer [P = 0.0001 by Fisher's exact test; odds ratio (OR), 29.7; 95% confidence interval (95% CI), 8.2-106.6]. For CA19-9, there was a trend towards a significant association (P = 00.7; OR, 4.5; 95% CI, 1-18.7, respectively). Diagnostic values of elevated CA125 and CA19-9 at screening increased when the study analysis was restricted to patients who developed a cancer within 1 year (P < 0.0001 and P = 0.018, respectively) or to patients without interstitial lung disease (P = 0.00001; OR, 133; 95% CI, 6.5-2733 and P = 0.027; OR, 9; 95% CI, 1.5-53, respectively). Individual comparisons of the baseline and the second CA125 value showed that three of the eight patients with cancers versus 3 of the 76 patients without, displayed an increase of their CA125 level (P = 0.01 by Fisher's exact test). We conclude that CA125 and CA19-9 assessment could be useful markers of the risk of developing tumors for patients with dermatomyositis and polymyositis and should therefore be included in the search for cancer in dermatomyositis/polymyositis patients, especially for patients without interstitial lung disease.
Risk Factors for Melanoma by Body Site
Authors: Cho Eunyoung , Rosner Bernard A. , Colditz Graham A.
Published: September 2005

It has been hypothesized that cutaneous melanoma at different anatomic sites develops through divergent pathways. We examined this hypothesis prospectively. We followed 152,949 women and 25,204 men free of cancer at baseline for up to 14 years in three large prospective studies. We examined risk factors for melanoma by anatomic location (head or neck, trunk, upper extremity, and lower extremity). Polytomous logistic regression was used to test the difference among risk factors by location of melanoma. A total of 511 incident cases of invasive melanoma (49 head or neck, 188 trunk, 98 upper extremity, and 176 lower extremity) were included in the analysis. Compared with females, males had a higher risk of developing melanoma on the head or neck and trunk. History of severe and painful sunburn was most strongly related to melanoma of upper extremity; individuals with >10 burns had a 6.86-fold (95% confidence interval, 2.62-18.00) higher risk of melanoma of upper extremity compared with those with no burns (P for trend < 0.0001; P for difference by body site = 0.04). Number of moles was most strongly related to melanoma of the trunk; the multivariate relative risk for having >10 moles was 4.67 (95% confidence interval, 3.07-7.11) compared with having no moles (P for trend < 0.0001; P for difference by body site = 0.04). Age, family history of melanoma, and hair color did not statistically differ by anatomic site of the cancer. These data support divergent etiologic pathways of melanoma development by anatomic sites.
Association of Susceptibility Alleles in ELAC2/HPC2, RNASEL/HPC1, and MSR1 with Prostate Cancer Severity in European American and African American Men
Authors: Rennert Hanna , Zeigler-Johnson Charnita M. , Addya Kathakali , Finley Matthew J. , Walker Amy H. , Spangler Elaine , Leonard Debra G.B. , Wein Alan , Malkowicz S. Bruce , Rebbeck Timothy R.
Published: September 2005

Reported associations of ELAC2/HPC2, RNASEL/HPC1, and MSR1 with prostate cancer have been inconsistent and understudied in African Americans. We evaluated the role of 16 sequence variants in these genes with prostate cancer using 888 European American and 131 African American cases, and 473 European American and 163 African American, controls. We observed significant differences in ELAC2, RNASEL, and MSR1 allele frequencies by race. However, we did not observe significant associations between prostate cancer and any variants examined for both races combined. Associations were observed when stratified by race, family history, or disease severity. European American men homozygous for MSR1 IVS7delTTA had an elevated risk for localized stage [odds ratio, (OR), 3.5; 95% confidence interval (95% CI), 1.4-6.9], low-grade (OR, 3.2; 95% CI, 1.4-7.3) disease overall, and with low-grade (OR, 2.9; 95% CI, 1.2-7.2) or late-stage disease (OR, 5.2; 95% CI, 1.1-25.7) in family history–negative African Americans. MSR1 Arg293X was associated with family history–negative high-grade disease (OR, 4.0; 95% CI, 1.1-14.1) in European Americans. RNASEL Arg462Gln was associated with low-grade (OR, 1.5; 95% CI, 1.04-2.2) and early-stage (OR, 1.5; 95% CI, 1.02-2.1) disease in family history–negative European Americans. In family history–positive individuals, Arg462Gln was inversely associated with low-grade (OR, 0.43; 95% CI, 0.21-0.88) and low-stage (OR, 0.46; 95% CI, 0.22-0.95) disease. In African Americans, Arg462Gln was associated with positive family history high-stage disease (OR, 14.8; 95% CI, 1.6-135.7). Meta-analyses revealed significant associations of prostate cancer with MSR1 IVS7delTTA, −14,742 A>G, and Arg293X in European Americans; Asp174Tyr in African Americans; RNASEL Arg462Gln in European American's overall and in family history–negative disease; and Glu265X in family history–positive European Americans. Therefore, MSR1 and RNASEL may play a role in prostate cancer progression and severity.
Catechol-O-Methyl-Transferase Functional Polymorphism and Nicotine Dependence: an Evaluation of Nonreplicated Results
Authors: Redden David T. , Shields Peter G. , Epstein Leonard , Wileyto E. Paul , Zakharkin Stanislav O. , Allison David B. , Lerman Caryn
Published: September 2005

Review articles have focused attention on and cited possible reasons for the nonreplication of genetic association studies. Herein, we illustrate how one might work through these possible reasons to make a judgment about the most plausible reason(s) when faced with two or more studies which yield seemingly inconsistent results. In the first study, 342 treatment-seeking smokers were genotyped for the Val108Met polymorphism in the functional catechol-O-methyl-transferase (COMT) locus. Alleles coding Val at codon 108 are denoted as H and those coding Met are denoted as L. An association between presence of the “H” (high activity) allele and pretreatment level of nicotine dependence level using the Fagerstrom Test for Nicotine Dependence was detected (P = 0.0072), after controlling for baseline body mass index (BMI, kg/m2), depression symptoms, and age. To validate this initial finding, 443 treatment-seeking smokers from an independent smoking cessation clinical trial were genotyped for the COMT polymorphism. Within the second study, no association between presence of the “H” allele and nicotine dependence was detected (P = 0.6418) after controlling for baseline BMI, depression symptoms, and age. We critically reviewed both studies with regard to often cited reasons for nonreplication, including type I error, population stratification, low statistical power, and imprecise measures of phenotype. Although in our opinion the failure to replicate the initial association in the second study is likely either the result of low statistical power to detect a small effect or effect heterogeneity, thorough analyses failed to definitively identify the reason for nonreplication.
The Biology of Tobacco and Nicotine: Bench to Bedside
Authors: Dennis Phillip A. , Van Waes Carter , Gutkind J. Silvio , Kellar Kenneth J. , Vinson Charles , Mukhin Alexey G. , Spitz Margaret R. , Bailey-Wilson Joan E. , Yeh Grace Chao , Anderson Lucy M. , Wiest Jonathan S.
Published: September 2005

Strong epidemiologic evidence links smoking and cancer. An increased understanding of the molecular biology of tobacco-related cancers could advance progress toward improving smoking cessation and patient management. Knowledge gaps between tobacco addiction, tumorigenesis, and cancer brought an interdisciplinary group of investigators together to discuss “The Biology of Nicotine and Tobacco: Bench to Bedside.” Presentations on the signaling pathways and pathogenesis in tobacco-related cancers, mouse models of addiction, imaging and regulation of nicotinic receptors, the genetic basis for tobacco carcinogenesis and development of lung cancer, and molecular mechanisms of carcinogenesis were heard. Importantly, new opportunities to use molecular biology to identify and abrogate tobacco-mediated carcinogenesis and to identify high-risk individuals were recognized.
Changes in Serum Proteomic Patterns by Presurgical α-Tocopherol andl-Selenomethionine Supplementation in Prostate Cancer
Authors: Kim Jeri , Sun Peiyu , Lam Ying-Wai , Troncoso Patricia , Sabichi Anita L. , Babaian Richard J. , Pisters Louis L. , Pettaway Curtis A. , Wood Christopher G. , Lippman Scott M. , McDonnell Timothy J. , Lieberman Ronald , Logothetis Christopher , Ho Shuk-Mei
Published: September 2005

Background: Evidence of the chemopreventive effects of the dietary antioxidants α-tocopherol (vitamin E) and l-selenomethionine (selenium) comes from secondary analysis of two phase III clinical trials that found treatment with these antioxidants reduced the incidence of prostate cancer. To determine the effects of selenium and vitamin E in blood and prostate tissue, we undertook a preoperative feasibility study complementary to the currently ongoing Selenium and Vitamin E Cancer Prevention Trial.

Methods: Forty-eight patients with clinically localized prostate cancer enrolled on this 2 × 2 factorial design study were randomized to take selenium, vitamin E, both, or placebo for 3 to 6 weeks before prostatectomy. Sera were collected from patients before and after dietary supplementation. Thirty-nine patients were evaluable, and 29 age-matched disease-free men served as controls. Mass profiling of lipophilic serum proteins of lower molecular weight (2-13.5 kDa) was conducted, and mass spectra data were analyzed using custom-designed software.

Results: Weighted voting analyses showed a change in sera classification from cancerous to healthy for some patients with prostate cancer after dietary intervention. ANOVA analysis showed significantly different treatment effects on prediction strength changes among the four groups at a 95% confidence level. Eliminating an outlying value and performing post hoc analysis using Fisher's least significant difference method showed that effects in the group treated with the combination were significantly different from those of the other groups.

Conclusion: In sera from patients with prostate cancer, selenium and vitamin E combined induced statistically significant proteomic pattern changes associated with prostate cancer–free status.
Effects of Electron-Beam Irradiation on Whole Genome Amplification
Authors: Bergen Andrew W. , Qi Ying , Haque Kashif A. , Welch Robert A. , Garcia-Closas Montserrat , Chanock Stephen J. , Vaught Jim , Castle Philip E.
Published: September 2005

Electron-beam (E-beam) irradiation, currently being used to sterilize mail addressed to selected ZIP codes in the United States, has significant negative effects on the genomic integrity of DNA extracted from buccal-cell washes. We investigated the yield, composition, and genotyping performance of whole genome amplified DNA (wgaDNA) derived from 24 matched samples of E-beam–irradiated and nonirradiated genomic DNA (gDNA) as a model for the effects of degraded gDNA on the performance of whole genome amplification. gDNA was amplified using the Multiple Displacement Amplification method. Three methods of DNA quantification analysis were used to estimate the yield and composition of wgaDNA, and 65 short tandem repeat and single nucleotide polymorphism genotyping assays were used to evaluate the genotyping performance of irradiated and nonirradiated gDNA and wgaDNA. Compared with wgaDNA derived from nonirradiated gDNA, wgaDNA derived from irradiated gDNA exhibited a significantly reduced yield of wgaDNA and significantly reduced short tandem repeat and single nucleotide polymorphism genotyping completion and concordance rates (P < 0.0001). Increasing the amount of irradiated gDNA input into whole genome amplification improved genotyping performance of wgaDNA but not to the level of wgaDNA derived from nonirradiated gDNA. Multiple Displacement Amplification wgaDNA derived from E-beam–irradiated gDNA is not suitable for genotyping analysis.
Insulin-like Growth Factor Polymorphisms and Colorectal Cancer Risk
Authors: Morimoto Libby M. , Newcomb Polly A. , White Emily , Bigler Jeannette , Potter John D.
Published: September 2005

Several modifiable lifestyle factors, such as physical activity, obesity, and postmenopausal hormone use, have been associated with colorectal cancer risk. It has been hypothesized that some or all of these factors may mediate their effects through alterations in insulin-like growth factor-1 (IGF-1) and its binding proteins (IGFBP). To evaluate the role of IGFs in colorectal cancer, we examined the relationship of two common genetic polymorphisms in IGF-1 (a cytosine-adenosine dinucleotide repeat) and IGFBP-3 (a G → C single nucleotide polymorphism) with colorectal cancer risk, as well as their potential modification by physical activity, body mass index (BMI), and postmenopausal hormone use. Subjects included 782 male and female colorectal cancer cases diagnosed between 1998 and 2002 and reported to the statewide registry in the metropolitan Seattle area, and 503 age- and sex-matched cancer-free population controls. Colorectal cancer was modestly associated with having an IGF-1 genotype other than homozygous for 19 repeats (odds ratio, 1.3; 95% confidence interval, 1.0-1.6) and having the GG IGFBP-3 genotype (odds ratio, 1.3; 95% confidence interval, 1.0-1.8). There was evidence that IGF-1 genotype modified the relationship between BMI and colorectal cancer among women, such that high BMI increased risk of colorectal cancer only among those with the 19/19 genotype (Pinteraction = 0.02). IGFBP-3 genotype was also a significant effect modifier of the relationship between risk factors and colorectal cancer: The positive association between BMI and colorectal cancer was observed only among men (Pinteraction < 0.01) and women (Pinteraction = 0.06) with the GG genotype; the inverse association between postmenopausal hormone use and colorectal cancer was observed only among women with the GG genotype (P = 0.01) and the inverse association between physical activity and colorectal cancer was observed only among men who carried the C allele (P < 0.01). The current study provides some support for a role of IGFs in colorectal cancer etiology, particularly in mediating the relationship of common risk factors (physical activity, BMI, and postmenopausal hormone use).
No Association between Gastroesophageal Reflux and Cancers of the Larynx and Pharynx
Authors: Nilsson Magnus , Chow Wong-Ho , Lindblad Mats , Ye Weimin
Published: September 2005

Purpose: To examine the proposed relation between gastroesophageal reflux disease and cancers of the larynx and pharynx.

Experimental Design: A cohort of 66,965 patients with discharge diagnoses of heartburn, hiatal hernia, or esophagitis was identified in the Swedish Inpatient Register. We observed a total of 376,622 person-years in the cohort. Identification of laryngeal and pharyngeal cancers was achieved through the Swedish Cancer Register. Standardized incidence ratios, the ratio of the observed to the expected number of cancers, derived from the general Swedish population and adjusted for sex, age, and calendar year, was used to estimate the relative risk.

Results: During follow-up, 30 cases of laryngeal and 31 cases of pharyngeal cancer were detected in the cohort. Slightly increased risks of laryngeal [relative risk, 1.6; 95% confidence interval (CI), 1.1-2.2] and pharyngeal carcinomas (relative risk, 1.9; 95% CI, 1.3-2.8) were observed in the total reflux cohort. After stratification to exclude cohort members with a diagnosis of alcoholism, no significant increase in the risk of laryngeal (relative risk, 1.3; 95% CI, 0.8-2.0) or pharyngeal carcinomas (relative risk, 1.0; 95% CI, 0.5-1.6) was found compared with the general population. Furthermore, there were no dose-response patterns of the risk for laryngeal and pharyngeal cancers with years of cohort follow-up, indicators of reflux severity, or specificity of reflux diagnosis.

Conclusion: This study provides no evidence in support of the proposed association between gastroesophageal reflux disease and cancers of the larynx or pharynx.
Serum Testosterone and the Risk of Prostate Cancer: Potential Implications for Testosterone Therapy
Authors: Parsons J. Kellogg , Carter H. Ballentine , Platz Elizabeth A. , Wright E. James , Landis Patricia , Metter E. Jeffrey
Published: September 2005

Objective: A potential risk of testosterone replacement therapy is an increase in the incidence of prostate cancer, but it is unclear whether higher levels of serum testosterone are associated with a higher risk of prostate cancer. We prospectively evaluated serum androgen concentrations and prostate cancer risk.

Method: Included were 794 members of the Baltimore Longitudinal Study of Aging. We estimated the rate ratio (RR) of prostate cancer by entering serial measures of serum total testosterone, dehydroepiandrosterone sulfate, sex hormone binding globulin, calculated free testosterone, and free testosterone index (FTI) into a Cox proportional hazards regression model with simple updating.

Results: Higher calculated free testosterone was associated with an increased age-adjusted risk of prostate cancer {RRs by quartile: 1.00, 1.52 [95% confidence interval (95% CI), 0.93-2.50], 1.16 (95% CI, 0.61-2.20), 2.59 (95% CI, 1.28-5.25); Ptrend = 0.03}, which persisted after excluding measures in men <45 years of age [RRs by quartile: 1.00, 1.33 (95% CI, 0.78-2.25), 1.26 (95% CI, 0.68-2.33), 1.89 (95% CI, 0.99-3.61); Ptrend = 0.03]. Compared to men with eugonadal FTI (≥0.153), men with hypogonadal FTI had a decreased risk of prostate cancer (RR, 0.51; 95% CI, 0.31-0.82).

Conclusion: Higher levels of calculated serum free testosterone are associated with an increased risk of prostate cancer. These findings suggest that men receiving testosterone therapy should be regularly monitored for prostate cancer and underscore the need for prospective trials of testosterone therapy incorporating incidence of prostate cancer as a primary safety end point.
Safety and Efficacy of Weight Training in Recent Breast Cancer Survivors to Alter Body Composition, Insulin, and Insulin-Like Growth Factor Axis Proteins
Authors: Schmitz Kathryn H. , Ahmed Rehana L. , Hannan Peter J. , Yee Douglas
Published: September 2005

Background: This randomized controlled trial assessed the safety and effects of twice-weekly weight training among recent breast cancer survivors. Outcomes included body size and biomarkers hypothesized to link exercise and breast cancer risk.

Methods: A convenience sample of 85 recent survivors was randomized into immediate and delayed treatment groups. The immediate group trained from months 0 to 12; the delayed treatment group served as a no exercise parallel comparison group from months 0 to 6 and trained from months 7 to 12. Measures at baseline, 6 and 12 months included body weight, height, body fat, lean mass, body fat %, and waist circumference, as well as fasting glucose, insulin, insulin resistance, insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding protein-1, IGFBP-2, and IGFBP-3. Injury reporting was standardized.

Results: The intervention resulted in significant increases in lean mass (0.88 versus 0.02 kg, P < 0.01), as well as significant decreases in body fat % (−1.15% versus 0.23%, P = 0.03) and IGF-II (−6.23 versus 28.28 ng/mL, P = 0.02) comparing immediate with delayed treatment from baseline to 6 months. Within-person changes experienced by delayed treatment group participants during training versus no training were similar. Only one participant experienced a study related injury that prevented continued participation.

Conclusion: Twice-weekly weight training is a safe exercise program for recent breast cancer survivors that may result in increased muscle mass, as well as decreased body fat % and IGF-II. The implications of these results on cancer recurrence or survival may become more evident with longer exercise intervention trials among breast cancer survivors.
Tissue-Specific Attenuation of Endogenous DNA I-Compounds in Rats by Carcinogen Azoxymethane: Possible Role of Dietary Fish Oil in Colon Cancer Prevention
Authors: Zhou Guo-Dong , Popovic Natasa , Lupton Joanne R. , Turner Nancy D. , Chapkin Robert S. , Donnelly Kirby C.
Published: September 2005

I-compounds are bulky covalent DNA modifications that are derived from metabolic intermediates of nutrients. Some I-compounds may play protective roles against cancer, aging, and degenerative diseases. Many carcinogens and tumor promoters significantly reduce I-compound levels gradually during carcinogenesis. Colon cancer is the second leading cause of cancer death in the United States, whereas cancer of the small intestine is relatively rare. Here we have studied levels of I-compounds in DNA of colon and duodenum of male Sprague-Dawley rats treated with azoxymethane. The effects of dietary lipids (fish oil or corn oil) on colon and duodenal DNA I-compounds were also investigated. Rats fed a diet containing fish oil or corn oil were treated with 15 mg/kg azoxymethane. Animals were terminated 0, 6, 9, 12, or 24 hours after injection. I-compound levels were analyzed by the nuclease P1–enhanced 32P-postlabeling assay. Rats treated with azoxymethane displayed lower levels of I-compounds in colon DNA compared with control groups (0 hour). However, I-compound levels in duodenal DNA were not diminished after azoxymethane treatment. Animals fed a fish oil diet showed higher levels of I-compounds in colonic DNA compared with corn oil groups (mean adduct levels for fish and corn oil groups were 13.35 and 10.69 in 109 nucleotides, respectively, P = 0.034). Taken together, these results support claims that fish oil, which contains a high level of ω-3 polyunsaturated fatty acids, may have potent chemopreventive effects on carcinogen-induced colon cancer. The fact that duodenal I-compounds were not diminished by azoxymethane treatment may have been due to the existence of tissue-specific factors protecting against carcinogenesis. In conclusion, our observations show that endogenous DNA adducts may serve not only as sensitive biomarkers in carcinogenesis and cancer prevention studies, but are also helpful to further our understanding of the chemopreventive properties of ω-3 fatty acids and mechanisms of carcinogenesis.
Lack of Association between EBV and Breast Carcinoma
Authors: Perrigoue Jacqueline G. , den Boon Johan A. , Friedl Andreas , Newton Michael A. , Ahlquist Paul , Sugden Bill
Published: September 2005

Multiple conflicting findings have been presented which indicate that EBV may be found in anywhere from 0% to 51% of breast carcinomas. When EBV has been found causally associated with other human cancers, its DNA and one or more of its viral products have been detected in most tumor cells of a given biopsy. To test whether EBV has such an association with breast cancer, we measured the number of viral DNA molecules per cell in matched normal and tumor biopsies from 45 patients using real-time quantitative PCR. In no case could EBV DNA consistently be detected, with either of two different probes, at levels above 0.1 molecules per cell in two sections of the tumor samples. These levels of detection match those detected in EBV-negative cell lines and therefore likely represent noise in the assays. Equally importantly, the distribution of these low signals was the same between tumors and their matched normal controls. We conclude that EBV does not contribute to the development of breast cancers as it does to epithelial cancers such as nasopharyngeal and gastric carcinomas or to Burkitt's and Hodgkin's lymphomas.
Ductal Lavage of Fluid-Yielding and Non–Fluid-Yielding Ducts in BRCA1 and BRCA2 Mutation Carriers and Other Women at High Inherited Breast Cancer Risk
Authors: Kurian Allison W. , Mills Meredith A. , Jaffee Margo , Sigal Bronislava M. , Chun Nicolette M. , Kingham Kerry E. , Collins Laura C. , Nowels Kent W. , Plevritis Sylvia K. , Garber Judy E. , Ford James M. , Hartman Anne-Renee
Published: September 2005

Objective: Nipple fluid production and atypical breast duct cells in women at high risk of breast cancer have been associated with further increased risk. Most publications on ductal lavage for cell collection report cannulating fluid-yielding ducts only. We report lavage of fluid-yielding and non–fluid-yielding ducts in women at high inherited breast cancer risk.

Methods: A pilot breast cancer screening study including ductal lavage was conducted in 75 women at high inherited risk, 56 (74.7%) of whom had BRCA1/2 mutations. Ductal lavage was attempted in any duct identifiable with a catheter.

Results: Ducts were successfully catheterized in 60 of 75 patients (80%). Successfully catheterized patients were younger (median age 41 versus 53 years, P = 0.0003) and more often premenopausal (51.7% versus 20%, P = 0.041). Thirty-one successfully catheterized patients [51.6%, 95% confidence interval (39.4-63.9%)] had non–fluid-yielding ducts only. Seventeen patients [28.3% (18.5-40.9%)] had atypical cells. Twelve of seventeen [70.6% (46.8-87.2%)] samples with atypia were from non–fluid-yielding ducts. Patients with non–fluid-yielding ducts (versus fluid-yielding ducts) were more likely to have had prior cancer (48.4% versus 17.2%, P = 0.014) or chemotherapy (45.2% versus 17.2%, P = 0.027); this was also true in patients with atypia from non–fluid-yielding ducts.

Conclusion: Successfully lavaged women were younger and more often premenopausal. Atypical cells can be found in non–fluid-yielding ducts in patients at high inherited breast cancer risk. Non–fluid-yielding ducts, and atypia from non–fluid-yielding ducts, are more common in patients with prior cancer and chemotherapy. Larger studies are needed to identify risk factors and prognostic significance associated with atypia and non–fluid-yielding ducts in high-risk populations, and define their role as biomarkers.
XRCC1Polymorphisms and Cancer Risk: A Meta-analysis of 38 Case-Control Studies
Authors: Hu Zhibin , Ma Hongxia , Chen Feng , Wei Qingyi , Shen Hongbing
Published: September 2005

Several potential functional polymorphisms (Arg194Trp, Arg280His, Arg399Gln) in the DNA base excision repair gene X-ray repair cross-complementing group 1 (XRCC1) have been implicated in cancer risk. Our meta-analysis on total of 11,957 cancer cases and 14,174 control subjects from 38 published case-control studies showed that the odds ratio (OR) for the variant genotypes (Trp/Trp + Arg/Trp) of the Arg194Trp polymorphism, compared with the wild-type homozygote (Arg/Arg), was 0.89 [95% confidence interval (95% CI), 0.81-0.98] for all tumor types without between-study heterogeneity. Similarly, the overall risk for the combined variant genotypes (His/His + Arg/His) of the Arg280His, compared with the wild homozygote (Arg/Arg), was 1.19 (95% CI, 1.00-1.42). However, there was no main effect in either recessive or dominant modeling for the Arg399Gln, and the variant Gln/Gln homozygote was not associated with overall cancer risk (OR, 1.01; 95% CI, 0.90-1.14). The analyses suggest that XRCC1 Arg194Trp, Arg280His polymorphisms may be biomarkers of cancer susceptibility and a single larger study with thousands of subjects and tissue-specific biochemical and biological characterization is warranted to further evaluate potential gene-to-gene and gene-to-environment interactions on XRCC1 polymorphisms and cancer risk.
Screening for Deleterious Nonsynonymous Single-Nucleotide Polymorphisms in Genes Involved in Steroid Hormone Metabolism and Response
Authors: Johnson Melissa M. , Houck John , Chen Chu
Published: September 2005

To facilitate selection of single-nucleotide polymorphisms (SNP) for molecular epidemiologic studies investigating the hormonal carcinogenesis hypothesis, we used two sequence homology–based tools [Sort Intolerant from Tolerant (SIFT) and Polymorphism Phenotype (PolyPhen)] to predict the potential impact a nonsynonymous SNP (nsSNP), which results in an amino acid substitution, may have on the activity of proteins encoded by genes involved in the steroid hormone metabolism and response pathway. We screened 137 variants. Of these, 28% were predicted by SIFT and PolyPhen as having a potentially damaging effect on protein function. Investigation into the association of these variant alleles with hormone-related cancers may prove to be fruitful.
Flavonoids and Breast Cancer Risk in Italy
Authors: Bosetti Cristina , Spertini Luana , Parpinel Maria , Gnagnarella Patrizia , Lagiou Pagona , Negri Eva , Franceschi Silvia , Montella Maurizio , Peterson Julie , Dwyer Johanna , Giacosa Attilio , La Vecchia Carlo
Published: September 2005

Few epidemiologic studies have investigated the potential relation between flavonoids and breast cancer risk. We have applied recently published data on the composition of foods and beverages in terms of six principal classes of flavonoids (i.e., flavanones, flavan-3-ols, flavonols, flavones, anthocyanidines, and isoflavones) on dietary information collected in a large-case control study of breast cancer conducted in Italy between 1991 and 1994. The study included 2,569 women with incident, histologically confirmed breast cancer, and 2,588 hospital controls. Odds ratios (OR) and 95% confidence intervals were estimated by multiple logistic regression models. After allowance for major confounding factors and energy intake, a reduced risk of breast cancer was found for increasing intake of flavones (OR, 0.81, for the highest versus the lowest quintile; P-trend, 0.02), and flavonols (OR, 0.80; P-trend, 0.06). No significant association was found for other flavonoids, including flavanones (OR, 0.95), flavan-3-ols (OR, 0.86), anthocyanidins (OR, 1.09), as well as for isoflavones (OR, 1.05). The findings of this large study of an inverse association between flavones and breast cancer risk confirm the results of a Greek study.
The 1944-1945 Dutch Famine and Subsequent Overall Cancer Incidence
Authors: Elias Sjoerd G. , Peeters Petra H.M. , Grobbee Diederick E. , van Noord Paulus A.H.
Published: September 2005

Caloric restriction seems to be the most potent dietary intervention to protect against a variety of cancers in animals. We investigated whether overall cancer risk is affected in humans after exposure to a brief famine, followed by a period of abundance. We used data of ∼15,000 women who were exposed at various degrees to the 1944-1945 Dutch famine at ages between 2 and 33 years. Between 1983 and 1986, these women were asked about their individual experiences of famine exposure (“absent,” “moderate,” or “severe exposure”). During follow-up until January 2000, 1,602 new cancer cases were identified by the regional cancer registry. We assessed the relation between famine and total cancer risk by weighted Cox regression models, in which a 15% random sample was used to represent person-years lived in the entire cohort. In these models, we adjusted for potential confounders. Overall cancer risk was increased in women having been severely famine exposed compared with women having been unexposed (hazard ratio, 1.25; 95% confidence interval, 1.01-1.55). Exclusion of breast cancer cases from our analyses showed that this increase in risk was largely driven by the previously reported increase in breast cancer risk: women who were severely exposed to the famine were at a 1.12 (95% confidence interval, 0.87-1.43) times increased risk of non-breast cancer compared with the unexposed. In conclusion, we found no indications that this brief famine has affected overall cancer risk, exclusive of breast cancer. Counteracting increased caloric intake following the famine, however, may have obscured any relation.
The MTHFR C677T Polymorphism and Colorectal Cancer: The Multiethnic Cohort Study
Authors: Le Marchand Loïc , Wilkens Lynne R. , Kolonel Laurence N. , Henderson Brian E.
Published: September 2005

Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in the metabolism of folate, a nutrient that has been inversely related to colorectal cancer risk. The common C677T variant in the MTHFR gene results in a reduced activity of this enzyme, thereby increasing the availability of folate for the production of thymidylate and purine for DNA synthesis and repair. We investigated the association of the 677TT genotype with colorectal cancer in a case-control study of 822 cases and 2,021 controls nested within the Multiethnic Cohort Study. The Multiethnic Cohort Study is a large prospective study of men and women of Japanese, White, African American, Latino, and Native Hawaiian origin, residing in Hawaii and Los Angeles. After adjusting for covariates, we found an inverse association between colorectal cancer risk and the TT genotype, with odds ratios (OR; and 95% confidence intervals) for the CC, CT, and TT genotypes of 1.00, 1.01 (0.84-1.21), and 0.77 (0.58-1.03), respectively. This association was similar in both sexes, stronger at high levels of folate intake, and limited to light and nondrinkers (P for interaction with ethanol = 0.02). An analysis by subsite (rectum versus colon) and stage (regional/distant versus in situ/localized) showed that the inverse association with the TT genotype was limited to colon tumors, especially those diagnosed at an advanced stage. The OR for the TT versus CC genotype for early- and late-stage colon cancer was 0.88 (0.58-1.33) and 0.52 (0.32-0.85), respectively (P for difference in OR = 0.04). The frequency of the T allele was relatively low in African Americans (0.13) and Native Hawaiians (0.22), consistent with their greater likelihood of presenting at a late stage when diagnosed with colorectal cancer. This study corroborates previous findings of an inverse association of the MTHFR 677TT genotype with colorectal cancer, especially at high levels of folate and low levels of ethanol intake. It also suggests that this effect may be specific to advanced colon cancer.
Oral Contraceptive Use, Reproductive Factors, and Colorectal Cancer Risk: Findings from Wisconsin
Authors: Nichols Hazel B. , Trentham-Dietz Amy , Hampton John M. , Newcomb Polly A.
Published: September 2005

We investigated the association of oral contraceptive (OC) use and reproductive factors with colorectal cancer risk in a large population-based case-control study. Cases were women ages 20 to 74 years, living in Wisconsin, with a new diagnosis of colon (n = 1,122) or rectal (n = 366) cancer. Control participants were randomly selected from population lists of similarly aged female Wisconsin residents (n = 4,297). Risk factor information was collected through structured telephone interviews. Compared with never users, OC users had an odds ratio (OR) of 0.89 [95% confidence interval (95% CI), 0.75-1.06] for colorectal cancer. OC use associations did not differ significantly between colon and rectal cancer sites; however, when compared with never users, recent OC users (<14 years) seemed at reduced risk of rectal cancer (OR, 0.53; 95% CI, 0.28-1.00). Women with age at first birth older than the median (23 years) had 0.83 times the risk of colon cancer compared with women with age at first birth below the median (95% CI, 0.70-0.98). We observed an inverse trend between increasing parity and rectal cancer risk (P = 0.05). Compared with nulliparous women, women with five or more births had 0.66 times the risk of rectal cancer (95% CI, 0.43-1.02). Compared with postmenopausal women, premenopausal women were at reduced risk (OR, 0.67; 95% CI, 0.47-0.97) of colorectal cancer. No significant associations were observed between colorectal cancer risk and age at menarche or age at menopause. These findings suggest differential roles of reproductive factors in colon and rectal cancer etiology.
Design Options for Molecular Epidemiology Research within Cohort Studies
Authors: Rundle Andrew G. , Vineis Paolo , Ahsan Habibul
Published: September 2005

Past discussions of the relative strengths of nested case-control and case-cohort designs have not fully considered cohorts with stored biological samples in which biomarker analyses are planned. Issues related to biomarker analyses can affect an investigator's choice of design and the conduct of these two designs. The key issues identified are effects of analytic batch, long-term storage, and freeze-thaw cycles on biomarkers. In comparison with the nested case-control design, the case-cohort design is less able to handle these challenges. Problems arise because most implementations of the case-cohort design do not allow for simultaneous evaluation of biomarkers in cases and reference group members, and there is no matching. By design, the nested case-control study controls for storage duration and the batching of biological samples from cases and controls is logistically simple. The allowance for matching also means that subjects can be matched on the number of freeze-thaw cycles experienced by the biological sample. However, the matching generates complex data sets that can be more difficult to analyze, and the costly biomarker data generated from the controls has few uses outside of testing the specific hypotheses of the study. In addition, because the same subject can serve as a control and a case, or multiple times as a control, biomarker analyses and sample batching can be more complex than initially anticipated. However, in total, of the two designs, the nested case-control study is better suited for studying biomarkers that can be influenced by analytic batch, long-term storage, and freeze-thaw cycles.
Comparison of Prostate-Specific Antigen and Hormone Levels among Men in Singapore and the United States
Authors: Cheng Iona , Yu Mimi C. , Koh Woon-Puay , Pike Malcolm C. , Kolonel Laurence N. , Henderson Brian E. , Stram Daniel O.
Published: September 2005

Prostate cancer incidence rates markedly vary between countries. The highest rates of prostate cancer are observed in Western countries such as the United States, whereas the lowest rates are seen in Asian countries such as Singapore. To gain an understanding of the difference in prostate cancer burden between low-risk and high-risk populations, we examined serum prostate-specific antigen (PSA) levels among Singapore-Chinese men (n = 315) from the Singapore Chinese Health Study and African-American (n = 440), U.S. White (n = 355), U.S. Latino (n = 523), and Japanese-American (n = 349) men from the Hawaii-Los Angeles Multiethnic Cohort Study. All men had no history of prostate cancer at the time of blood draw. PSA measurements were assayed by one centralized diagnostic facility. Testosterone and 3α-androstanediol glucuronide levels were examined in a subsample of men. Scheffe's multiple comparison tests were used to evaluate differences in PSA and hormone levels between groups. PSA levels among the Singapore-Chinese (geometric mean = 1.43 ng/mL) were similar to that of African-Americans (1.46 ng/mL), U.S. Whites (1.28 ng/mL), and Japanese-Americans (1.22 ng/mL) and significantly higher than U.S. Latinos (1.18 ng/mL; P = 0.038). Although there was a strong correlation (R2 = 0.89) between PSA levels and U.S. ethnic group–specific prostate cancer incidence rates before PSA screening (1983-1987), the levels among the Singapore-Chinese completely failed to relate to their low incidence rate. Testosterone and 3α-androstanediol glucuronide levels did not reflect racial/ethnic patterns of disease. Our results highlight a potentially large group of Singapore-Chinese men with undiagnosed prostate cancer. Given that the overall mortality rate of prostate cancer in Singapore is low, these undiagnosed cancers may be of nonaggressive type. Alternatively, PSA may be a poor marker of prostate cancer in this low-risk population.
Energy Balance and Breast Cancer Risk
Authors: Malin Alecia , Matthews Charles E. , Shu Xiao-Ou , Cai Hui , Dai Qi , Jin Fan , Gao Yu-Tang , Zheng Wei
Published: September 2005

We evaluated the hypothesis that a pattern of behavioral exposures indicating positive energy balance [i.e., less exercise/sport activity, high body mass index (BMI), or high energy intake] would be associated with an increased breast cancer risk in the Shanghai Breast Cancer Study, a population-based study of 1,459 incident breast cancer cases and 1,556 age frequency-matched controls. Participants completed in-person interviews that collected information on breast cancer risk factors, usual dietary intake and physical activity in adulthood. Anthropometric indices were measured. Odds ratios and 95% confidence intervals were estimated by logistic regression to describe the individual and joint effects of the exposures on breast cancer risk. Lack of exercise/sport activity, low occupational activity, and high BMI were all individually associated with increased risk of breast cancer [odds ratios (OR) ranged from 1.49 to 1.86]. In general, women with lower exercise/sport activity level and higher BMI, or those with higher energy intake, were at an increased risk compared with women who reported more exercise/sport activities, had lower BMIs, or reported less energy intake. There was a significant multiplicative interaction (P = 0.02) between adult exercise/sport activity and BMI, with inactive women in the upper BMI quartile being at increased risk (OR, 2.16; 95% confidence interval, 1.25-3.74) compared with their active and lean counterparts. This association was stronger in postmenopausal than in premenopausal women, and nonexercising postmenopausal women with higher BMIs were at substantially increased risk (OR, 4.74; 95% confidence interval, 2.05-12.20). Our study suggests that promotion of behavior patterns that optimize energy balance (weight control and increasing physical activity) may be a viable option for breast cancer prevention.
Transition Metals in Personal Samples of PM2.5 and Oxidative Stress in Human Volunteers
Authors: Sørensen Mette , Schins Roel P.F. , Hertel Ole , Loft Steffen
Published: September 2005

Ambient particulate matter (PM) has been associated with increased risk of lung cancer. One proposed mechanism is that PM induces oxidative stress mediated by transition metals contained within this mixture. We examined the relationship between the personal exposure to water-soluble transition metals in PM2.5 and oxidative DNA damage. In 49 students from central Copenhagen, we determined PM2.5 exposure by personal sampling twice in 1 year, and measured in these PM2.5 samples the concentration of the soluble transition metals vanadium, chromium, iron, nickel, copper, and platinum. Collected lymphocytes and 24-hour urine samples were analyzed for DNA damage in terms of 7-hydro-8-oxo-2′-deoxyguanosine (8-oxodG). We found that the 8-oxodG concentration in lymphocytes was significantly associated with the vanadium and chromium concentrations with a 1.9% increase in 8-oxodG per 1 μg/L increase in the vanadium concentration and a 2.2% increase in 8-oxodG per 1 μg/L increase in the chromium concentration. We have previously reported that in this study population the personal exposure to PM2.5 was associated with an increase in 8-oxodG in lymphocytes. However, vanadium and chromium were associated with the 8-oxodG concentration in lymphocytes independently of the PM2.5 mass concentration. The four other transition metals were not associated with 8-oxodG in lymphocytes and none of the transition metals was significantly associated with 8-oxodG in urine. Our results could indicate that vanadium and chromium present in PM2.5 have an effect on oxidative DNA damage that is independent of particle mass and/or other possible toxic compounds contained within this particulate mixture.