bluuebunny/crossref_metadata_2025_split huggingface dataset:
XRCC1 and XRCC3 Polymorphisms and Their Role as Effect Modifiers of Unsaturated Fatty Acids and Antioxidant Intake on Colorectal Adenomas Risk
Authors: Stern Mariana C. , Siegmund Kimberly D. , Corral Román , Haile Robert W. 
Published: September 2005

Abstract
Whereas animal and in vitro studies support a role of unsaturated fatty acids in colon carcinogenesis, the epidemiologic evidence is inconclusive. Using a large sigmoidoscopy-based case-control study (753 cases and 799 controls) in Los Angeles County, we investigated possible associations between single-nucleotide polymorphisms in the XRCC1 (codons 194 Arg/Trp and codon 399 Arg/Gln) and XRCC3 (codon 241 Thr/Met) genes and colorectal adenoma risk and their possible role as modifiers of the effect of monounsaturated fatty acid, the ratio of ω-6/ω-3 polyunsaturated fatty acids, and antioxidant intake. We found no evidence of associations between the XRCC1 codon 194 Arg/Trp or Trp/Trp genotypes and the XRCC3 codon 241 Thr/Met or Met/Met genotypes. Subjects with the XRCC1 Gln/Gln genotype were inversely associated with adenoma risk (odds ratio, 0.6; 95% confidence interval, 0.4-0.9; P = 0.01) when compared with subjects with Arg/Arg and Arg/Gln genotypes combined. We found no evidence of gene-dietary fat interactions for the XRCC3 codon 241 polymorphism. However, our data suggest an XRCC1-unsaturated fat interaction. High monounsaturated fatty acid intake was associated with adenoma risk only among subjects with the XRCC1 codon 194 Arg/Arg and codon 399 Gln/Gln combined genotypes (P for interaction = 0.018). High ω-6/ω-3 polyunsaturated fatty acid ratios were associated with adenoma risk among subjects with the XRCC1 codon 194 Arg/Arg and codon 399 Gln/Gln or the codon 194 Arg/Trp or Trp/Trp and codon 399 Arg/Arg or Arg/Gln combined genotypes (P for interaction = 0.026). These interactions were not modified by antioxidant intake. However, low antioxidant intake was associated with an inverse association only among subjects with the XRCC1 codon 194 Arg/Trp or Trp/Trp and codon 399 Arg/Arg or Arg/Gln combined genotypes (P for interaction = 0.022), which was independent of unsaturated fat intake. Our data suggest that the XRCC1 codon 194 and codon 399 single nucleotide polymorphisms may modify the effect of unsaturated fatty acid and antioxidant intake and that this XRCC1 effect modification may explain, in part, previously reported inconsistencies on the role of unsaturated fatty acids and adenoma risk.
Cyp17, Urinary Sex Steroid Levels and Breast Cancer Risk in Postmenopausal Women
Authors: Onland-Moret N. Charlotte , van Gils Carla H. , Roest Mark , Grobbee Diederick E. , Peeters Petra H.M. 
Published: September 2005

Abstract
Endogenous sex hormones play an important role in the etiology of breast cancer. Polymorphisms in genes encoding for enzymes involved in steroidogenesis may therefore play a role in breast cancer risk. Cytochrome P450c17α (Cyp17) functions at key branch points in human steroidogenesis. A T→C transition (A1 and A2 allele) in the 5′ untranslated region may be associated with increased expression of Cyp17. Using a case-cohort design, we studied the effects of the A2 allele on endogenous sex hormone levels and breast cancer risk within a large population-based cohort (n = 9,349) in the Netherlands (the DOM-cohort). Cyp17 genotype was determined in 335 incident postmenopausal breast cancer cases, which occurred after follow-up (median time to follow-up, 19 years) of the entire cohort, and in a random sample of 373 women (subcohort). Concentrations of estrone (E1), estradiol (E2), testosterone, 5α-androstane-3α, 17β-diol (3αD), and creatinine were measured in first-morning urine samples. Only among women with body mass index (BMI) &lt; 25 kg/m2 was the A2A2 genotype associated with higher levels of E1, E2, and 3αD compared with a group of women with either the A1A1 or the A1A2 genotype (e.g., geometric means of E1 in ng/mgcreatinine: A2A2, 2.23; A1A1/A1A2, 1.47; P = 0.03). Adjusted breast cancer rate ratios for women with the A1A2 or A2A2 genotype compared with women with the A1A1 genotype were 0.96 (0.68-1.37) and 0.80 (0.47-1.35), respectively. These results did not differ between women with low and high BMI. In conclusion, this paper shows that women with low BMI and the A2A2 genotype had higher endogenous sex steroid levels compared with women with the A1A1 genotype. However, these increased sex steroid levels are not translated into an increased breast cancer risk in these women.
Exploratory Study of Ovarian Intraepithelial Neoplasia
Authors: Brewer Molly A. , Ranger-Moore James , Baruche Amy , Alberts David S. , Greene Mark , Thompson Deborah , Liu Yun , Davis John , Bartels Peter H. 
Published: September 2005

Abstract
Purpose: This was an exploratory study to test two hypotheses related to potential epithelial precursors to ovarian cancer: (a) histologically normal ovarian surface epithelium exhibited changes in the nuclear chromatin pattern, which indicate an ovarian abnormality, and (b) such changes were detectable in the ovarian surface epithelium of cancer-free subjects who were at high risk for ovarian cancer.
Experimental Design: Ovaries were carefully collected to avoid damage to the surface epithelium. Five-micron-thick histologic sections were cut and stained with H&E. High-resolution images were recorded from the ovarian surface epithelium and from the underlying stroma of ovaries from normal women (10 cases), women at high risk of developing ovarian cancer (7 cases), and histologically normal areas adjacent to ovarian cancer (3 cases). Karyometric features and measurements of nuclear abnormality were computed for 3,390 epithelial nuclei. Discriminant function analyses and unsupervised learning algorithms were employed to define deviations from normal and to identify the subpopulations of nuclei exhibiting these changes.
Results: Epithelium from ovaries harboring a malignant lesion had changes in the nuclear chromatin pattern consistent with a second phenotype, which were not visually detected with histopathologic surveillance. This phenotype was also present in the ovaries obtained from women at increased risk of ovarian cancer, suggesting that it may represent a premalignant abnormality. These changes were statistically significant.
Conclusion: The observed changes in karyometric features were sufficiently distinct to warrant further study as both diagnostic and prognostic biomarkers for early detection and prevention of ovarian cancer.
Modifiable Risk Factors Associated with Clearance of Type-Specific Cervical Human Papillomavirus Infections in a Cohort of University Students
Authors: Richardson Harriet , Abrahamowicz Michal , Tellier Pierre-Paul , Kelsall Gail , du Berger Roxane , Ferenczy Alex , Coutlée François , Franco Eduardo L. 
Published: September 2005

Abstract
Background: Previous findings regarding risk factors for human papillomavirus (HPV) persistence, other than viral determinants, identified from prospective cohort studies have been inconsistent in part because study designs have differed with respect to differing HPV detection methods and varying lengths of follow-up time. Therefore, the objectives of this study were to continue the search for epidemiologic risk factors of persistent cervical HPV infections and determine what behaviors differed between those women with transient HPV infections and those women who cannot clear their type-specific HPV infections.
Methods: Female university students (n = 621) in Montreal were followed for 24 months at 6-month intervals. At each visit, a cervical cell specimen was collected. HPV DNA was detected using the MY09/MY11 PCR protocol and 27 HPV genotypes were identified by the line blot assay (Roche Molecular Systems, Inc., Alameda, CA). Proportional hazards regression was used to estimate the crude and adjusted hazard ratios of clearing a type-specific high-risk (n = 222) or low-risk (n = 105) HPV infection over time according to specific baseline and time-dependent covariates.
Results: Daily consumption of vegetables seemed to increase the rate of HPV clearance independent of type. The use of tampons was associated with a reduced rate of high-risk HPV clearance, whereas regular condom use was associated with an increased rate of low-risk HPV clearance only.
Conclusion: Some proactive measures can be taken to increase the rate of HPV clearance, and there may be some differences between the sets of predictors of low-risk and high-risk HPV clearance.
Chromosomal Instability in Peripheral Blood Lymphocytes and Risk of Prostate Cancer
Authors: El-Zein Randa , Gu Yun , Sierra Monica S. , Spitz Margaret R. , Strom Sara S. 
Published: September 2005

Abstract
Prostate cancer is an extremely complex disease, and it is likely that chromosomal instability is involved in the genetic mechanism of tumorigenesis. Several chromosomes have been labeled as “players” in the development of prostate cancer, among them chromosome 1 and X chromosome have been reported to harbor prostate cancer susceptibility loci. However, there is little information regarding the background levels of chromosome instability in these patients. In this pilot study, we examined spontaneous chromosome instability in short-term lymphocyte cultures from 126 study subjects, 61 prostate cancer patients, and 65 healthy controls. We evaluated chromosomal instability using a fluorescence in situ hybridization assay using two probes targeting specific regions on X chromosome and chromosome 1. Our results showed a significantly higher mean level of spontaneous breaks involving the X chromosome in patients compared with controls (mean ± SE, 2.41 ± 0.26 and 0.62 ± 0.08, respectively; P &lt; 0.001). Similarly, chromosome 1 spontaneous breaks were significantly higher among cases compared with controls (mean ± SE, 1.95 ± 0.24 and 1.09 ± 0.16, respectively; P &lt; 0.001). Using the median number of breaks in the controls as the cutoff value, we observed an odds ratio (95% confidence interval) of 15.53 (5.74 - 42.03; P &lt; 0.001) for spontaneous X chromosome breaks and 3.71 (1.60 - 8.63; P &lt; 0.001) for chromosome 1 breaks and risk of development of prostate cancer. In conclusion, our preliminary results show that spontaneous chromosome instability could be a risk factor for prostate cancer.
Ki-67 Expression in Benign Breast Ductal Cells Obtained by Random Periareolar Fine Needle Aspiration
Authors: Khan Qamar J. , Kimler Bruce F. , Clark Julie , Metheny Trina , Zalles Carola M. , Fabian Carol J. 
Published: September 2005

Abstract
Ki-67 expression in ductal cells obtained by random periareolar fine needle aspiration (RPFNA) is currently being used as a response biomarker in phase II breast cancer chemoprevention trials; however, Ki-67 in RPFNA has not been well studied as a risk predictor for cancer, which would support its use as a response indicator. We examined the expression of Ki-67 in RPFNA specimens with hyperplasia ± atypia obtained from 147 women at high risk for development of breast cancer. Median Ki-67 was 1.4% (range 0-24%). Ki-67 was higher in specimens from women &lt;50 versus those ≥50 (median 2% versus 0.6%; P = 0.006) and from premenopausal women versus postmenopausal women (P = 0.037); however, hormone replacement therapy (predominately low-dose estrogen without progestins) had no effect. By univariate analysis, Ki-67 was positively correlated with ductal cell number (P = 0.001) and hyperplasia with atypia (P = 0.007). By multivariable analysis, the proportion of ductal cells expressing Ki-67 was again predicted by cell number, which, in turn, was predicted by cytologic atypia. The association of Ki-67 expression with cytologic atypia, a known risk factor for development of breast cancer, provides preliminary justification for its use as a response biomarker in phase II chemoprevention trials.
Interindividual Variability in Response to Sodium Dichromate–Induced Oxidative DNA Damage: Role of the Ser326Cys Polymorphism in the DNA-Repair Protein of 8-Oxo-7,8-Dihydro-2′-Deoxyguanosine DNA Glycosylase 1
Authors: Lee Amanda J. , Hodges Nikolas J. , Chipman James K. 
Published: September 2005

Abstract
Although the genotoxic mechanism(s) of hexavalent chromium (CrVI) carcinogenicity remain to be fully elucidated, intracellular reduction of CrVI and concomitant generation of reactive intermediates including reactive oxygen species and subsequent oxidative damage to DNA is believed to contribute to the process of carcinogenesis. In the current study, substantial interindividual variation (7.19-25.84% and 8.79-34.72% tail DNA as assessed by conventional and FPG-modified comet assay, respectively) in levels of DNA strand breaks after in vitro treatment of WBC with sodium dichromate (100 μmol/L, 1 hour) was shown within a group of healthy adult volunteers (n = 72) as assessed by both comet and formamidopyrimidine glycosylase–modified comet assays. No statistically significant correlation between glutathione S-transferases M1 or T1, NADPH quinone oxidoreductase 1 (codon 187) and X-ray repair cross complementation factor 1 (codon 194) genotypes and individual levels of DNA damage were observed. However, individuals homozygous for the Cys326 8-oxo 7,8-dihydro-2′-deoxyguanosine glycosylase 1 (OGG1) polymorphism had a statistically significant elevation of formamidopyrimidine glycosylase–dependent oxidative DNA damage after treatment with sodium dichromate when compared with either Ser326/Ser326 or Ser326/Cys326 individuals (P = 0.008 and P = 0.003, respectively). In contrast, no effect of OGG1 genotype on background levels of oxidative DNA damage was observed. When individuals were divided on the basis of OGG1 genotype, Cys326/Cys326 individuals had a statistically significant (P &lt; 0.05, one-way ANOVA followed by Tukey test) higher ratio of oxidative DNA damage to plasma antioxidant capacity than either Ser326/Ser326 or Ser326/Cys326 individuals. The results of this study suggest that the Cys326/Cys326 OGG1 genotype may represent a phenotype that is deficient in the repair of 8-oxo-7,8-dihydro-2′-deoxyguanosine, but only under conditions of cellular oxidative stress. We hypothesize that this may be due to oxidation of the Cys326 residue. In conclusion, the homozygous Cys326 genotype may represent a biomarker of individual susceptibility of lung cancer risk in individuals that are occupationally exposed to CrVI.
Association between Mammographic Breast Density and Breast Cancer Tumor Characteristics
Authors: Aiello Erin J. , Buist Diana S.M. , White Emily , Porter Peggy L. 
Published: September 2005

AbstractObjective: Few studies have examined the association between breast density and breast cancer tumor characteristics. We examined the association between hormonal, proliferative, and histologic tumor characteristics and mammographic breast density in women with breast cancer.Methods: We conducted a cross-sectional analysis in 546 women diagnosed with invasive breast cancer to evaluate the associations between breast density and tumor size, lymph node status, lymphatic or vascular invasion, histologic grade, nuclear grade, tumor differentiation, mitotic index, tumor necrosis, Ki-67 proliferation, estrogen receptor, progesterone receptor, p53, p27, cyclin E, Bcl-2, and C-erb-B2 invasion. Breast density was classified as fatty (Breast Imaging Reporting and Data System code 1 or 2; n = 373) or dense (Breast Imaging Reporting and Data System code 3 or 4; n = 173) for the cancer-free breast. A single pathologist measured all tumor markers. We examined whether the relationships were modified by interval cancer or screen-detected cancer.Results: Women with a tumor size &gt;1.0 cm were more likely to have dense breasts compared with women with a tumor size ≤1.0 cm after adjusting for confounders (odds ratio, 2.0; 95% confidence interval, 1.2-3.4 for tumor sizes 1.1-2.0 cm; odds ratio, 2.3; 95% confidence interval, 1.3-4.4 for tumor sizes 2.1-10 cm). Tumor size, lymph node status, and lymphatic or vascular invasion were positively associated with breast density among screen-detected cancers. Histologic grade and mitotic index were negatively associated with breast density in women diagnosed with an interval cancer.Conclusions: These results suggest that breast density is related to tumor size, lymph node status, and lymphatic or vascular invasion in screen-detected cancers. Additional studies are needed to address whether these associations are due to density masking the detection of some tumors, a biological relationship, or both.
Oral Contraceptive Use and Risk of Early-Onset Breast Cancer in Carriers and Noncarriers of BRCA1 and BRCA2 Mutations
Authors: Milne Roger L. , Knight Julia A. , John Esther M. , Dite Gillian S. , Balbuena Ronald , Ziogas Argyrios , Andrulis Irene L. , West Dee W. , Li Frederick P. , Southey Melissa C. , Giles Graham G. , McCredie Margaret R.E. , Hopper John L. , Whittemore Alice S. ,   for the Breast Cancer Family Registry
Published: September 2005

Abstract
Background: Recent oral contraceptive use has been associated with a small increase in breast cancer risk and a substantial decrease in ovarian cancer risk. The effects on risks for women with germ line mutations in BRCA1 or BRCA2 are unclear.
Methods: Subjects were population-based samples of Caucasian women that comprised 1,156 incident cases of invasive breast cancer diagnosed before age 40 (including 47 BRCA1 and 36 BRCA2 mutation carriers) and 815 controls from the San Francisco Bay area, California, Ontario, Canada, and Melbourne and Sydney, Australia. Relative risks by carrier status were estimated using unconditional logistic regression, comparing oral contraceptive use in case groups defined by mutation status with that in controls.
Results: After adjustment for potential confounders, oral contraceptive use for at least 12 months was associated with decreased breast cancer risk for BRCA1 mutation carriers [odds ratio (OR), 0.22; 95% confidence interval (CI), 0.10-0.49; P &lt; 0.001], but not for BRCA2 mutation carriers (OR, 1.02; 95% CI, 0.34-3.09) or noncarriers (OR, 0.93; 95% CI, 0.69-1.24). First use during or before 1975 was associated with increased risk for noncarriers (OR, 1.52 per year of use before 1976; 95% CI, 1.22-1.91; P &lt; 0.001).
Conclusions: There was no evidence that use of current low-dose oral contraceptive formulations increases risk of early-onset breast cancer for mutation carriers, and there may be a reduced risk for BRCA1 mutation carriers. Because current formulations of oral contraceptives may reduce, or at least not exacerbate, ovarian cancer risk for mutation carriers, they should not be contraindicated for a woman with a germ line mutation in BRCA1 or BRCA2.
A Simulation Model for Colorectal Cancer Screening: Potential of Stool Tests with Various Performance Characteristics Compared with Screening Colonoscopy
Authors: Haug Ulrike , Brenner Hermann 
Published: September 2005

Abstract
Objective: Many new stool tests intended to detect neoplastic cells or cell products are developed at present for colorectal cancer (CRC) screening. The aim of this study was to simulate a population-based screening setting to assess and compare the potential for early detection and prevention of CRC of screening based on stool tests with different sensitivity and specificity and of screening with colonoscopy as a primary screening tool.
Method: A Markov model was developed aimed to estimate the proportion of CRC cases which are early detected or prevented due to screening as well as the number of equired stool tests and colonoscopies per early detected or prevented CRC case. Model outcomes were calculated for the offer of annual stool testing from age 55 to 74 in combination with colonoscopic follow-up of positive test results and for the offer of screening colonoscopy as a primary screening tool at ages 55 and 65. The long-lasting risk reduction of colonoscopy allowing the removal of precancerous lesions was taken into account quantitatively.
Results: For a variety of stool tests with different performance characteristics, the proportion of CRC cases early detected or prevented was estimated to be higher for stool testing in combination with colonoscopic follow-up of positive test results compared with screening colonoscopy assuming levels of compliance to be expected for the respective screening scheme. Optimizing performance characteristics of stool tests in terms of detecting precancerous lesions, in addition to those in terms of detecting CRC, seemed to be crucial for maximizing effectiveness of CRC screening with stool tests.
Conclusion: Screening based on new stool tests with colonoscopic follow-up of positive test results might offer a high potential for early detection or prevention of CRC.
Thyroid Cancer Susceptibility and THRA1 and BAT-40 Repeats Polymorphisms
Authors: Baida Aida , Farrington Susan M. , Galofré Pere , Marcos Ricard , Velázquez Antonia 
Published: September 2005

Abstract
Although genetic and environmental factors have been identified in the etiology of thyroid cancer, the specific genetic implications in sporadic thyroid tumors are poorly understood but, as in other common cancers, low-penetrance susceptibility genes are believed to be crucial in the tumorigenesis processes. Here, we have carried out a case-control study to investigate whether there is an association between THRA1 CA repeat or BAT-40 A repeat polymorphisms and thyroid cancer risk. The THRA1 repeat resides in the thyroid hormone receptor-α1 gene, which is associated with thyroid cancer and whose expression depends on the THRA1 repeat size. We also analyzed the BAT-40 repeat that maps to chromosome 1, a region known to be involved in thyroid cancer. This repeat is located in the 3-β-hydroxysteroid dehydrogenase gene that is associated with prostate cancer susceptibility. The THRA1 repeat was genotyped in 212 thyroid cancer patients and 141 controls of a Spanish population. From these individuals, 207 patients and 138 controls were also analyzed for the BAT-40 marker. No significant difference in the THRA1 allele distribution between patients and controls was found, although short alleles (&lt;128 bp) might have some protective effect on thyroid cancer risk of carriers (odds ratio, 0.50; 95% confidence interval, 0.22-1.13; P = 0.094). By contrast, the BAT-40 allele distribution in patients was significantly different with respect to control (P = 0.035). Essentially, the difference were found in the genotypes involving the 111- to 115-bp allele range, which seem to be associated with a protective effect on thyroid cancer susceptibility in the studied population (odds ratio, 0.18; 95% confidence interval, 0.01-0.57; P = 0.02). Therefore, our results indicate that the BAT-40 containing region and to a less extend the thyroid hormone receptor-α1 gene are related to thyroid cancer susceptibility. To our knowledge, this is the first study reporting the identification of genetic factors for thyroid cancer susceptibility.