bluuebunny/crossref_metadata_2025_split huggingface dataset:
Claudin-4, Mitogen-Activated Protein Kinase Kinase 4, and Stratifin Are Markers of Gastric Adenocarcinoma Precursor Lesions
Authors: Cunningham Steven C. , Kamangar Farin , Kim Min P. , Hammoud Sommer , Haque Raqeeb , Iacobuzio-Donahue Christine A. , Maitra Anirban , Ashfaq Raheela , Hustinx Steven , Heitmiller Richard E. , Choti Michael A. , Lillemoe Keith D. , Cameron John L. , Yeo Charles J. , Schulick Richard D. , Montgomery Elizabeth 
Published: March 2006

Abstract
Approximately 23,000 new gastric cancer cases and 12,000 associated deaths occur annually in the United States. Intestinal metaplasia and gastric epithelial dysplasia are precursor lesions to gastric adenocarcinoma, but are not readily detectable clinically, radiographically, or endoscopically. A noninvasive method of precursor detection would require the ability to distinguish precursor lesions from adjacent normal mucosa. In search of such markers, tissue microarrays were prepared for 133 patients of resected gastric adenocarcinoma. Tissue microarrays contained primary cancer, normal stomach, intestinal metaplasia, and gastric epithelial dysplasia and were probed with antibodies against nine potential markers that were either identified in a database of genes overexpressed in gastric adenocarcinoma or were already of interest to our laboratory: claudin-4, mitogen-activated protein kinase kinase 4 (MKK4), 14-3-3σ (stratifin), S100A4, mesothelin, fascin, topoisomerase IIα, HER-2/neu, and epithelial growth factor receptor. Three markers discriminated gastric adenocarcinoma precursor lesions from normal gastric mucosa. Claudin-4 expression was present in 36 intestinal metaplasia lesions (100%) and 14 gastric epithelial dysplasia lesions (100%), but in only 16 normal stomach samples (15%). MKK4 expression was present in 24 intestinal metaplasia lesions (89%) and 12 gastric epithelial dysplasia lesions (100%), but in only 6 normal stomach samples (8%). Stratifin expression was present in 29 intestinal metaplasia lesions (97%) and 8 gastric epithelial dysplasia lesions (100%), but in only 2 normal stomach samples (3%). Sensitivity and specificity for detection of the precursor lesion intestinal metaplasia were 100% and 85%, respectively, for claudin-4; 89% and 92%, respectively, for MKK4; and 97% and 97%, respectively, for stratifin. In primary cancers, 123 of 125 (98.4%) were positive for claudin-4, 116 of 126 (94%) for MKK4, and 111 of 120 (92%) for stratifin. In conclusion, claudin-4, MKK4, and stratifin immunolabeling detects precursor lesions of gastric adenocarcinoma that are otherwise clinically, radiographically, and endoscopically inapparent. These findings may prove useful in the diagnosis and therapeutic targeting of gastric adenocarcinoma precursor lesions. (Cancer Epidemiol Biomarkers Prev 2006;15(2):281–7)
Telomere Length in the Colon Declines with Age: a Relation to Colorectal Cancer?
Authors: O'Sullivan Jacintha , Risques Rosa Ana , Mandelson Margaret T. , Chen Lu , Brentnall Teresa A. , Bronner Mary P. , MacMillan Melissa P. , Feng Ziding , Siebert Joseph R. , Potter John D. , Rabinovitch Peter S. 
Published: March 2006

Abstract
Telomeres shorten with age, which may be linked to genomic instability and an increased risk of cancer. To explore this association, we analyzed telomere length in normal colorectal tissue of individuals at different ages using quantitative-fluorescence in situ hybridization (Q-FISH) and quantitative-PCR (Q-PCR). Using Q-FISH, we also examined the histologically normal epithelium adjacent to, or distant from, colon adenomas and cancers, in addition to the neoplasms. Q-FISH and Q-PCR showed that telomere length was inversely associated with age until ∼ages 60 to 70; surprisingly, beyond this age, telomere length was positively associated with age. This association was found exclusively in epithelial, and not in stromal, cells. Peripheral blood lymphocytes showed an inverse association between telomere length and age, but without any apparent increase in telomere length in the oldest individuals. Telomere length in larger adenoma lesions (&gt;2 cm) was significantly shorter than in normal adjacent (P = 0.004) or normal distant (P = 0.05) tissue from the same individuals. However, telomere length in histologically normal epithelium adjacent to cancers or in adenomas &lt;2 cm was not statistically different from that of the normal distant mucosa or from normal controls, evidence that a telomere-shortening field effect was not present. We suggest that the positive association between telomere length and age in the oldest patients is a consequence of selective survival of elderly patients with long colonocyte telomeres. (Cancer Epidemiol Biomarkers Prev 2006;15(3):573–7)
The CHEK2*1100delC Allelic Variant and Risk of Breast Cancer: Screening Results from the Breast Cancer Family Registry
Authors: Bernstein Jonine L. , Teraoka Sharon N. , John Esther M. , Andrulis Irene L. , Knight Julia A. , Lapinski Robert , Olson Eric R. , Wolitzer Abigail L. , Seminara Daniela , Whittemore Alice S. , Concannon Patrick 
Published: March 2006

Abstract
CHEK2, a serine-threonine kinase, is activated in response to agents, such as ionizing radiation, which induce DNA double-strand breaks. Activation of CHEK2 can result in cell cycle checkpoint arrest or apoptosis. One specific variant, CHEK2*1100delC, has been associated with an increased risk of breast cancer. In this population-based study, we screened 2,311 female breast cancer cases and 496 general population controls enrolled in the Ontario and Northern California Breast Cancer Family Registries for this variant (all controls were Canadian). Overall, 30 cases and one control carried the 1100delC allele. In Ontario, the weighted mutation carrier frequency among cases and controls was 1.34% and 0.20%, respectively [odds ratio (OR), 6.65; 95% confidence interval (95% CI), 2.37-18.68]. In California, the weighted population mutation carrier frequency in cases was 0.40%. Across all cases, 1 of 524 non-Caucasians (0.19%) and 29 of 1,775 Caucasians (1.63%) were mutation carriers (OR, 0.12; 95% CI, 0.02-0.89). Among Caucasian cases &gt;45 years age at diagnosis, carrier status was associated with history of benign breast disease (OR, 3.18; 95% CI, 1.30-7.80) and exposure to diagnostic ionizing radiation (excluding mammography; OR, 3.21; 95% CI, 1.13-9.14); compared with women without exposure to ionizing radiation, the association was strongest among women exposed &gt;15 years before diagnosis (OR, 4.28; 95% CI, 1.50-12.20) and among those who received two or more chest X-rays (OR, 3.63; 95% CI, 1.25-10.52). These data supporting the biological relevance of CHEK2 in breast carcinogenesis suggest that further studies examining the joint roles of CHEK2*1100delC carrier status and radiation exposure may be warranted.(Cancer Epidemiol Biomarkers Prev 2006;15(2):348–52)
Endogenous Sex Hormone Levels and Mammographic Density among Postmenopausal Women
Authors: Tamimi Rulla M. , Hankinson Susan E. , Colditz Graham A. , Byrne Celia 
Published: March 2006

AbstractBackground: Mammographic density is one of the strongest predictors of breast cancer risk. The mechanism by which breast density increases breast cancer risk is unclear although it has been hypothesized that breast density reflects cumulative exposure to estrogens.Methods: To evaluate this hypothesis, we conducted a cross-sectional study among 520 postmenopausal women in the Nurses' Health Study that examined the relation between circulating sex hormones and mammographic density. Women were postmenopausal and not taking exogenous hormones at the time of blood collection and mammogram. Percent breast density was measured from digitized mammograms using a computer-assisted method. Circulating estrone, estradiol, androstenedione, testosterone, DHEA, DHEA sulfate, sex hormone–binding globulin, progesterone, and prolactin were measured in plasma.Results: In contrast to the prior hypothesis, circulating estrogens were inversely related to percent mammographic density. The mean percent mammographic density was 25.6% among women in the lowest quartile of circulating estradiol compared with 14.4% among women in the highest quartile [Spearman correlation (r) = −0.22, P &lt; 0.0001]. Circulating estrogens alone explained 1% to 5% of the variation of mammographic density. Body mass index was positively associated with circulating estradiol levels (r = 0.45, P &lt; 0.0001) and inversely related to percent mammographic density (r = −0.51, P &lt; 0.0001). After adjustment for body mass index, there was no association between estradiol and breast density (r = 0.01, P = 0.81). Likewise, there was no relation between the other sex hormones measured or prolactin and mammographic density after adjustment for body mass index.Conclusion: These findings indicate that in postmenopausal women, mammographic density is independent of circulating sex hormone levels.
Physical Activity in Relation to Mammographic Density in the Dutch Prospect-European Prospective Investigation into Cancer and Nutrition Cohort
Authors: Suijkerbuijk Karijn P.M. , Van Duijnhoven Fränzel J.B. , Van Gils Carla H. , Van Noord Paulus A.H. , Peeters Petra H.M. , Friedenreich Christine M. , Monninkhof Evelyn M. 
Published: March 2006

Abstract
Background: Evidence accumulates that physical inactivity is one of the few modifiable risk factors for breast cancer. The mechanism through which physical inactivity affects breast cancer risk is not clear. The study aim was to investigate the association between physical activity and breast density because mammographic density is strongly associated with breast cancer risk.
Methods: We did a cross-sectional study in 620 women, of ages 49 to 68 years and participants of the Dutch Prospect-European Prospective Investigation into Cancer and Nutrition cohort. A self-administered questionnaire was used to obtain information on duration and intensity of physical activity (recreational, household, and occupational) during the year preceding study recruitment. A total activity index (inactive, moderately inactive, moderately active, and active) was estimated by combining all activity types. Percent and absolute breast density were determined on screening mammograms using a computer-aided method. Multivariate linear regression was used to examine the association between physical activity and breast density.
Results: Mean percent density was 35.3% [95% confidence interval (95% CI), 31.8-38.8] for the inactive category compared with 36.1% (95% CI, 33.0-39.2) for the active category. Mean absolute density values for the inactive and active category were 45.8 cm2 (95% CI, 40.9-50.7) and 42.6 cm2 (95% CI, 38.3-47.0), respectively. Subgroup analysis for postmenopausal women showed similar results, as did separate analyses for recreational and household activity.
Conclusions: The result does not support a relation between current physical activity and mammographic density in postmenopausal women. (Cancer Epidemiol Biomarkers Prev 2006;15(3):456–60)
Sexual Behavior, Condom Use, and Human Papillomavirus: Pooled Analysis of the IARC Human Papillomavirus Prevalence Surveys
Authors: Vaccarella Salvatore , Franceschi Silvia , Herrero Rolando , Muñoz Nubia , Snijders Peter J.F. , Clifford Gary M. , Smith Jennifer S. , Lazcano-Ponce Eduardo , Sukvirach Sukhon , Shin Hai-Rim , de Sanjosé Silvia , Molano Monica , Matos Elena , Ferreccio Catterina , Thi Hoang Anh Pham , Thomas Jaiye O. , Meijer Chris J.L.M. ,   IARC HPV Prevalence Surveys Study Group
Published: March 2006

AbstractHuman papillomavirus (HPV) is a sexually transmitted infection but it is unclear whether differences in transmission efficacy exist between individual HPV types. Information on sexual behavior was collected from 11 areas in four continents among population-based, age-stratified random samples of women of ages ≥15 years. HPV testing was done using PCR-based enzyme immunoassay. Unconditional logistic regression was used to estimate odds ratios (OR) of being HPV positive and corresponding 95% confidence intervals (95% CI). Variables were analyzed categorically. When more than two groups were compared, floating confidence intervals were estimated by treating ORs as floating absolute risks. A total of 11,337 women (mean age, 41.9 years) were available. We confirmed that lifetime number of sexual partners is associated with HPV positivity (OR for ≥2 versus 1, 1.86; 95% CI, 1.63-2.11) but the association was not a linear one for HPV18, 31, and 33 (i.e., no clear increase for ≥3 versus 2 sexual partners). Women who had multiple-type infection and high-risk HPV type infection reported a statistically nonsignificant higher number of sexual partners than women who had single-type and low-risk type infections, respectively. Early age at sexual debut was not significantly related to HPV positivity. Husband's extramarital sexual relationships were associated with an OR of 1.45 (95% CI, 1.24-1.70) for HPV positivity in their wives after adjustment for age and lifetime number of women's sexual partners. We did not observe a significant association with condom use. Our study showed an effect of both women's and their husbands' sexual behavior on HPV positivity. Furthermore, it suggests some differences in the pattern of the association between sexual behavior and different HPV types.(Cancer Epidemiol Biomarkers Prev 2006;15(2):326–33)
Variation in DNA Repair GenesERCC2, XRCC1, andXRCC3and Risk of Follicular Lymphoma
Authors: Ekström Smedby Karin , Lindgren Cecilia M. , Hjalgrim Henrik , Humphreys Keith , Schöllkopf Claudia , Chang Ellen T. , Roos Göran , Ryder Lars P. , Falk Kerstin I. , Palmgren Juni , Kere Juha , Melbye Mads , Glimelius Bengt , Adami Hans-Olov 
Published: March 2006

AbstractThe reasons for the positive association between skin cancer and non-Hodgkin's lymphoma are not known but may be due to common susceptibility involving suboptimal DNA repair. Therefore, we investigated selected polymorphisms and haplotypes in three DNA repair genes, previously associated with skin cancer and DNA repair capacity, in risk of follicular lymphoma, including possible gene interaction with cigarette smoking and sun exposure. We genotyped 19 single nucleotide polymorphisms (SNP) in the ERCC2, XRCC1, and XRCC3 genes in 430 follicular lymphoma patients and 605 controls within a population-based case-control study in Denmark and Sweden. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression and haplotype associations were assessed with a global score test. We observed no associations between variation in the ERCC2 and XRCC1 genes and follicular lymphoma risk. In XRCC3, increased risk of follicular lymphoma was suggested for rare homozygotes of three SNPs [Rs3212024: OR, 1.8 (95% CI, 1.1-2.8); Rs3212038: OR, 1.5 (95% CI, 1.0-2.4); Rs3212090: OR, 1.5 (95% CI, 1.0-2.5)]. These results were strengthened in current cigarette smokers. However, evidence of differences in XRCC3 haplotype distributions between follicular lymphoma cases and controls was weak, both overall and in current smokers. We conclude that polymorphic variation in the XRCC3 gene, but not in ERCC2 or XRCC1, may be of importance for susceptibility to follicular lymphoma, perhaps primarily in current smokers. The link between skin cancer and follicular lymphoma is unlikely to be mediated through common variation in the studied DNA repair gene polymorphisms. (Cancer Epidemiol Biomarkers Prev 2006;15(2)–65)
APC I1307K and the Risk of Prostate Cancer
Authors: Poynter Jenny N. , Cooney Kathleen A. , Bonner Joseph D. , White Kirsten A. , Tomsho Lynn P. , Rennert Gad , Gruber Stephen B. 
Published: March 2006

Abstract
The kin-cohort design has been proposed as an alternative to traditional case-control and cohort measures to evaluate inherited susceptibility to cancer in population-based studies. Here, we used this design to evaluate inherited susceptibility to prostate cancer associated with APC I1307K using data from the Molecular Epidemiology of Colorectal Cancer study. Two techniques were used to compare the incidence of prostate cancer in APC I1307K carriers. First, we compared the incidence of prostate cancer in relatives of mutation carriers and noncarriers using standard techniques for survival analysis. Second, we used the marginal maximum likelihood method for kin-cohort analysis to infer the genotypes in the relatives. We also evaluated APC I1307K in 75 Ashkenazi Jewish individuals with prostate cancer from 27 families enrolled in the University of Michigan Prostate Cancer Genetic Study. We observed a slightly increased risk of prostate cancer in relatives of APC I1307K carriers, however, this difference was not statistically significant (hazard ratio, 1.6; 95% confidence intervals, 0.7-3.4). Similar conclusions were drawn using both techniques for kin-cohort analysis. APC I1307K was found in 7.4% of families genotyped, which is slightly higher than the allele prevalence reported in Ashkenazi Jews in the general population. In addition, we did not observe loss of heterozygosity at APC or a somatic mutation near APC I1307K using microdissected tumor DNA from mutation carriers enrolled in the Prostate Cancer Genetic Study. Overall, the evidence for an association between APC I1307K and prostate cancer is not compelling. APC I1307K is unlikely to play a clinically meaningful role in susceptibility to prostate cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(3):468–73)
A Prospective Study of Calcium Intake and Incident and Fatal Prostate Cancer
Authors: Giovannucci Edward , Liu Yan , Stampfer Meir J. , Willett Walter C. 
Published: March 2006

Abstract
Prostate cancer is the most common incident cancer and the second leading cause of cancer mortality in U.S. males. Higher milk intake has been relatively consistently associated with an increased risk of prostate cancer, especially advanced prostate cancer. Some data suggest that high intake of calcium might account for this association, but this relationship remains controversial. We hypothesized that high calcium intake, possibly by lowering 1,25(OH)2 vitamin D levels, is associated with poorer differentiation in prostate cancer and thereby with fatal prostate cancer. We examined calcium intake in relation to prostate cancer risk using data from the Health Professionals Follow-up Study, a prospective cohort study of 47,750 male health professionals with no history of cancer other than nonmelanoma skin cancer at baseline. We assessed total, dietary, and supplementary calcium intake in 1986, 1990, 1994, and 1998, using a validated food frequency questionnaire. We calculated the multivariable relative risk (RR) and 95% confidence intervals (95% CI) using Cox proportional hazards regression. Over 16 years of follow-up, we identified 3,544 total cases of prostate cancer, 523 advanced (extraprostatic) cases, and 312 fatal cases. Higher calcium intake was not appreciably associated with total or nonadvanced prostate cancer but was associated with a higher risk of advanced and fatal prostate cancer [for fatal prostate cancer, compared with men whose long-term calcium intake was 500-749 mg/d (excluding supplement use of &lt;5 years); those with intakes of 1,500-1,999 mg/d had a RR, 1.87; 95% CI, 1.17-3.01; and those with ≥2,000 mg/d had a RR, 2.43; 95% CI, 1.32-4.48; Ptrend = 0.003]. Dietary calcium and supplementary calcium were independently associated with an increased risk. For high-grade prostate cancer (Gleason ≥ 7), an association was observed for high versus low calcium intake (RR, 1.89; 95% CI, 1.32-2.71; Ptrend = 0.005), but a nonsignificant, inverse association was observed for organ-confined, low-grade prostate cancer (RR, 0.79; 95% CI, 0.50-1.25; Ptrend = 0.09). In a sample of this cohort, higher calcium intake was associated with lower circulating 1,25(OH)2 vitamin D levels. Our findings suggest that calcium intakes exceeding 1,500 mg/d may be associated with a decrease in differentiation in prostate cancer and ultimately with a higher risk of advanced and fatal prostate cancer but not with well-differentiated, organ-confined cancers. (Cancer Epidemiol Biomarkers Prev 2006;15(2):203–10)
Data-Dredging Gene-Dose Analyses in Association Studies: Biases and their Corrections
Authors: Lee Wen-Chung , Huang Hsiao-Yuan 
Published: March 2006

Abstract
To examine the joint effect of multiple loci on disease risk, many case-control association studies used “gene-dose analyses.” However, some researchers defined high-risk genotypes (or alleles) as those that have higher genotypic (allelic) frequencies in the case group compared with the control group in the study. This will lead to the total number of the “high-risk” genotypes (alleles) tending to be higher for the cases than for the controls as well, even if none of the studied loci were related to the disease. Monte-Carlo simulations done in this study showed that such a “data-dredging” gene-dose analysis could produce grossly biased results. A permutation correction method was proposed which could correct the biases very effectively. (Cancer Epidemiol Biomarkers Prev 2005;14(12):3004–6)
Dairy, Calcium, and Vitamin D Intake and Postmenopausal Breast Cancer Risk in the Cancer Prevention Study II Nutrition Cohort
Authors: McCullough Marjorie L. , Rodriguez Carmen , Diver W. Ryan , Feigelson Heather Spencer , Stevens Victoria L. , Thun Michael J. , Calle Eugenia E. 
Published: March 2006

Abstract
Background: Calcium, vitamin D, and dairy products are highly correlated factors, each with potential roles in breast carcinogenesis. Few prospective studies have examined these relationships in postmenopausal women.
Methods: Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed questionnaire on diet, vitamin and mineral supplement use, medical history, and lifestyle in 1992 to 1993. After exclusion of women with a history of cancer and incomplete dietary data, 68,567 postmenopausal women remained for analysis. During follow-up through August 31, 2001, we identified 2,855 incident cases of breast cancer. Multivariate-adjusted rate ratios (RR) were calculated using Cox proportional hazards models.
Results: Women with the highest intake of dietary calcium (&gt;1,250 mg/d) were at a lower risk of breast cancer than those reporting ≤500 mg/d [RR, 0.80; 95% confidence interval (95% CI), 0.67-0.95; Ptrend = 0.02]; however, neither use of supplemental calcium nor vitamin D intake was associated with risk. Consumption starting at two or more servings of dairy products per day was likewise inversely associated with risk (RR, 0.81; 95% CI, 0.69-0.95; Ptrend = 0.002, compared with &lt;0.5 servings/d). The associations were slightly stronger in women with estrogen receptor–positive tumors comparing highest to lowest intake: dietary calcium (RR, 0.67; 95% CI, 0.51-0.88; Ptrend = 0.004); dairy products (RR, 0.73; 95% CI, 0.57-0.93; Ptrend = 0.0003), and dietary vitamin D (RR, 0.74; 95% CI, 0.59-0.93; Ptrend = 0.006).
Conclusions: Our results support the hypothesis that dietary calcium and/or some other components in dairy products may modestly reduce risk of postmenopausal breast cancer. The stronger inverse associations among estrogen receptor–positive tumors deserve further study. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2898–904)