bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Relative Importance of Genetics and Environment on Mammographic Density
Authors: Ursin Giske , Lillie Elizabeth O. , Lee Eunjung , Cockburn Myles , Schork Nicholas J. , Cozen Wendy , Parisky Yuri R. , Hamilton Ann S. , Astrahan Melvin A. , Mack Thomas 
Published: January 2009

Abstract
Background: Although several environmental factors predict mammographic density, estimates of its heritability have been quite high. We investigated whether part of the presumed heritability might be attributed to differential sharing of modifiable risk factors in monozygotic (MZ) and dizygotic (DZ) twins.
Methods: We measured percent and absolute mammographic density using mammograms from 257 MZ and 296 DZ twin pairs. The correlation of intrapair mammographic density was compared according to zygosity across strata of modifiable risk factors. Portions of variance attributable to additive genetic factors, shared environment, and individual environment were calculated using a variance component methodology in the entire set, and within twin pairs stratified by environmental trait similarity.
Results: Both percent density and absolute mammographic density were more highly correlated between MZ twins than DZ twins, but the correlations varied across strata. Body mass index (BMI) and parity strongly predicted differences in mammographic density within MZ twin pairs. After adjusting for covariates, 53% of the total variance in percent density and 59% of that in absolute density seemed attributable to genetic effects, but these estimates varied greatly by stratum. For twins dissimilar on BMI (difference &gt;2.5 kg/m2), the additive genetic component of absolute density was estimated at only 20% (±19%), and the common and individual environment at 21% (±14%) and 49%, respectively (P value for heterogeneity across BMI = 0.0001).
Conclusion: Our results confirm that the genome is an important determinant of mammographic density but suggest that an unknown portion of the mammographic density effect attributed to the genome may be due to shared modifiable environmental factors. (Cancer Epidemiol Biomarkers Prev 2009;18(1):102–12)
Male Circumcision and Serologically Determined Human Papillomavirus Infection in a Birth Cohort
Authors: Dickson Nigel P. , Ryding Janka , van Roode Thea , Paul Charlotte , Herbison Peter , Dillner Joakim , Skegg David C.G. 
Published: January 2009

AbstractCircumcision has been reported to protect against infection with human papillomavirus (HPV) in men, but results have been inconsistent. We followed males in a birth cohort born in Dunedin, New Zealand, in 1972 and 1973 from age 3 to 32 years. Seropositivity at age 32 years for the oncogenic types HPV-16 and 18, and the nononcogenic types 6 and 11, was studied in relation to maternal reports of circumcision status at age 3 for 450 men. Seropositivity to any of these types was associated with lifetime number of sexual partners (P = 0.03), and lower moral-religious emphasis of the family of origin (P &lt; 0.001). Circumcision was not found to be protective, with the adjusted odds ratio (95% confidence interval) for HPV6/11/16/18 seropositivity among the circumcised compared with the uncircumcised being 1.4 (0.89-2.2). (Cancer Epidemiol Biomarkers Prev 2009;18(1):177–83)
The Elevated Expression of a Mismatch Repair Protein Is a Predictor for Biochemical Recurrence After Radical Prostatectomy
Authors: Norris Alixanna M. , Gentry Michael , Peehl Donna M. , D'Agostino Ralph , Scarpinato Karin D. 
Published: January 2009

Abstract
Purpose: The inability to predict clinical outcome of prostate cancer is a major impediment to effective treatment decisions and patient counseling. New markers of recurrence are needed to improve the accuracy of risk assessment and treatment of prostate cancer. Our previous studies identified a mismatch repair protein, PMS2, to be elevated in prostate cancer; here, we investigate the prognostic potential of this marker. We hypothesized that the elevation of PMS2 would correlate with disease outcome.
Experimental Design: Retrospective quantitative immunohistochemistry was done to measure PMS2 in high-grade cancers of 166 men treated by radical prostatectomy with a biochemical recurrence rate of 56%. Associations between PMS2 levels, pathologic variables, and biochemical recurrence over time were determined.
Results: The mean level of PMS2 protein was consistently higher in both cancer-associated benign epithelium and cancer cells of patients who recurred, compared with nonrecurrent patients. PMS2 was an independent predictor of time-to-recurrence in Cox multivariate analyses and significantly stratified patients based on outcome. PMS2 was able to improve the sensitivity of total percent Gleason 4/5 as a risk factor for recurrence in this cohort.
Conclusions: PMS2 protein levels were shown to be a predictor of time-to-recurrence after surgery. This study is the first to document that the elevation of a mismatch repair protein negatively correlates with prognosis and has implications in patient diagnosis and molecular profiling. (Cancer Epidemiol Biomarkers Prev 2009;18(1):57–64)
The Association of Bone Mineral Density with Prostate Cancer Risk in the Osteoporotic Fractures in Men (MrOS) Study
Authors: Farhat Ghada N. , Taioli Emanuela , Cauley Jane A. , Zmuda Joseph M. , Orwoll Eric , Bauer Douglas C. , Wilt Timothy J. , Hoffman Andrew R. , Beer Tomasz M. , Shikany James M. , Daniels Nicholas , Chan June , Fink Howard A. , Barrett-Connor Elizabeth , Parsons J. Kellogg , Bunker Clareann H. ,   for the Osteoporotic Fractures in Men (MrOS) Study Group
Published: January 2009

Abstract
We investigated the association of bone mineral density (BMD) measures with prostate cancer (PCa) risk in older men enrolled in the Osteoporotic Fractures in Men Study. We hypothesized that men with higher BMD, a marker of exposure to endogenous sex hormones, would have an increased incidence of PCa. The cohort included 4,597 men (89% White, 65 years or older) with no prior history of PCa. Baseline total body, total hip, and spine BMD were assessed using dual energy X-ray absorptiometry. Prostate cancer was confirmed by review of medical records. Cox regression was used to assess the association of BMD quartiles with incident PCa, adjusting for age, body mass index, and other covariates. During an average follow-up of 5.2 years, 5.6% (n = 255) of men developed PCa. Total body BMD was inversely associated with incident PCa, with a significant trend for decreasing PCa risk with increasing BMD quartiles (Ptrend = 0.007). Men in the highest total body BMD quartile had a 41% reduced risk for PCa (hazard ratio, 0.59; 95% confidence interval, 0.40-0.86), compared with men in the lowest quartile. Total hip and spine BMD did not exhibit significant relationships with PCa. Associations of BMD measures differed for low-grade (Gleason sum, 2-6) versus high-grade tumors (Gleason sum, ≥7). Significant inverse relationships with high-grade disease were noted at the total body and total hip sites. However, no associations were observed with low-grade disease. Our results provide support for an inverse association between BMD and PCa risk. Possible pathophyisological mechanisms linking BMD and PCa should be elucidated. (Cancer Epidemiol Biomarkers Prev 2009;18(1):148–54)
Vitamin D Receptor Polymorphisms and Breast Cancer Risk: Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
Authors: McKay James D. , McCullough Marjorie L. , Ziegler Regina G. , Kraft Peter , Saltzman Barbara S. , Riboli Elio , Barricarte Aurelio , Berg Christine D. , Bergland Goran , Bingham Sheila , Brustad Magritt , Bueno-de-Mesquita H. Bas , Burdette Laurie , Buring Julie , Calle Eugenia E. , Chanock Stephen J. , Clavel-Chapelon Françoise , Cox David G. , Dossus Laure , Feigelson Heather Spencer , Haiman Christopher A. , Hankinson Susan E. , Hoover Robert N. , Hunter David J. , Husing Anika , Kaaks Rudolph , Kolonel Laurence N. , Le Marchand Loic , Linseisen Jakob , McCarty Catherine A. , Overvad Kim , Panico Salvatore , Purdue Mark P. , Stram Daniel O. , Stevens Victoria L. , Trichopoulos Dimitrios , Willett Walter C. , Yuenger Jeffrey , Thun Michael J. 
Published: January 2009

Abstract
Background: Vitamin D is hypothesized to lower the risk of breast cancer by inhibiting cell proliferation via the nuclear vitamin D receptor (VDR). Two common single nucleotide polymorphisms (SNP) in the VDR gene (VDR), rs1544410 (BsmI), and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokI ff genotype, which encodes a less transcriptionally active isoform of VDR, and reduced risk has been reported for the BsmI BB genotype, a SNP in strong linkage disequilibrium with a 3′-untranslated region, which may influence VDR mRNA stability.
Methods: We pooled data from 6 prospective studies in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium to examine associations between these SNPs and breast cancer among &gt;6,300 cases and 8,100 controls for each SNP using conditional logistic regression.
Results: The odds ratio (OR) for the rs2228570 (FokI) ff versus FF genotype in the overall population was statistically significantly elevated [OR, 1.16; 95% confidence interval (95% CI), 1.04-1.28] but was weaker once data from the cohort with previously published positive findings were removed (OR, 1.10; 95% CI, 0.98-1.24). No association was noted between rs1544410 (BsmI) BB and breast cancer risk overall (OR, 0.98; 95% CI, 0.89-1.09), but the BB genotype was associated with a significantly lower risk of advanced breast cancer (OR, 0.74; 95% CI, 0.60-0.92).
Conclusions: Although the evidence for independent contributions of these variants to breast cancer susceptibility remains equivocal, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status. (Cancer Epidemiol Biomarkers Prev 2009;18(1):297–305)
Human Papillomavirus Cofactors by Disease Progression and Human Papillomavirus Types in the Study to Understand Cervical Cancer Early Endpoints and Determinants
Authors: Wang Sophia S. , Zuna Rosemary E. , Wentzensen Nicolas , Dunn S. Terence , Sherman Mark E. , Gold Michael A. , Schiffman Mark , Wacholder Sholom , Allen Richard A. , Block Ingrid , Downing Kim , Jeronimo Jose , Carreon J. Daniel , Safaeian Mahboobeh , Brown David , Walker Joan L. 
Published: January 2009

Abstract
Human papillomavirus (HPV) cofactors for cervical cancer include smoking, multiparity, and oral contraceptive use, but their mechanisms of action are not fully understood. It is also unknown whether cofactors vary by HPV genotypes. The Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED) is a cross-sectional study comprising women referred to the University of Oklahoma from November 2003 to September 2007 for abnormal cervical screening results. Detailed questionnaire data and liquid cytology specimens were collected and the latter was genotyped for HPV using the LINEAR ARRAY HPV Genotyping Test. The present analysis includes women with both questionnaire and HPV data and diagnosed with &lt;CIN1 (n = 535), CIN1 (n = 497), CIN2 (n = 336), CIN3 (n = 292), and cancer (n = 80). We evaluated HPV types and cofactors among HPV-infected women by calculating odds ratios (OR) and 95% confidence intervals (95% CI) for CIN3 and CIN2 separately compared with &lt;CIN2 using a polytomous logistic regression model; cancers were excluded from further analysis due to the substantially higher ages of these women. We found that HPV-infected women with minor histologic or cytologic abnormalities (e.g., CIN1, ASCUS, and LSIL) were indistinguishable from those with normal histology/cytology and were thus combined to form the referent group (&lt;CIN2). Among women positive for oncogenic HPV, current smokers had a 2.5-fold increased risk for CIN3 (95% CI, 1.8-3.6) compared with nonsmokers. Among HPV16-infected women, current smokers had elevated risk for both CIN2 (OR, 1.9; 95% CI, 1.1-3.2) and CIN3 (OR, 2.7; 95% CI, 1.6-4.6). Our data suggest that non-HPV16-related CIN2 likely reflects a combination of CIN1 and CIN3 diagnosis, whereas HPV16-related CIN2 may indicate a precancerous state. Investigations on the molecular distinctions along the disease continuum of cervical pathogenesis by HPV type are needed. (Cancer Epidemiol Biomarkers Prev 2009;18(1):113–20)
Seasonal and Regional Contributors of 1-Hydroxypyrene among Children near a Steel Mill
Authors: Lee Mi-Sun , Eum Ki-Do , Lee Kiyoung , Kim Ho , Paek Domyung 
Published: January 2009

Abstract
Urinary 1-hydroxypyrene (1-OHP) is a biomarker of exposure to polycyclic aromatic hydrocarbons (PAH). Effect of residence on children's PAH exposure was reported among children living near a polluted area. Instead of a snapshot assessment, however, a temporal history of exposure characteristics needs to be assessed in the studies of chronic disease development such as cancer. The urinary 1-OHP measurements were repeated to determine regional effect of ambient air pollution on 1-OHP levels over extended periods. Two sites were chosen: (a) one site located near the steel mill (“nearby” site) and (b) the other site located at a longer distance from the mill (“remote” site). Spot urinary 1-OHP levels were measured from 72 children for 3 consecutive days per month, repeated over 9-month period. Compared with remote site, the nearby site had increased the urinary 1-OHP level by 62.3% [95% confidence interval (95% CI), 39.8-88.3%]. Other statistically significant factors that contributed to the level include sex [16.5% (95% CI, 1.2-34.1%) higher for girls than boys], consumption of charbroiled meat [16.5% (95% CI, 1.1-34.2%) higher], and an increase in PM10 [10.1% (95% CI, 4.8-15.7%) higher for the interquartile range increment]. Controlling for covariates, the 1-OHP levels were increased in the summer and fall compared with winter. The magnitude of the effects of both seasons had diminished after adjusting for PM10. This is the first report providing seasonal and regional contributors to environmental PAH exposure, assessed by urinary 1-OHP, with higher 1-OHP levels during summer when ambient pollution was also high. (Cancer Epidemiol Biomarkers Prev 2009;18(1):96–101)
DNA Repair Gene Variants Associated with Benign Breast Disease in High Cancer Risk Women
Authors: Jorgensen Timothy J. , Helzlsouer Kathy J. , Clipp Sandra C. , Bolton Judy Hoffman , Crum Rosa M. , Visvanathan Kala 
Published: January 2009

AbstractBenign breast disease (BBD) is a risk factor for breast cancer and may have a heritable component. Deficient DNA repair has been implicated in breast cancer etiology and may exert its effect before BBD, a known precursor. The association between allelic variants in DNA repair genes and BBD was examined in a cohort of women in Washington County, Maryland. BBD was defined by two criteria: (a) a physician diagnosis of BBD or fibrocystic disease and/or (b) a benign breast biopsy. 3,212 women without BBD at baseline were genotyped for 12 candidate single nucleotide polymorphisms in seven DNA repair genes. Of these women, 482 subsequently reported a diagnosis of BBD. The Cox model was used to calculate hazard ratios (HR). Variant alleles of XRCC1 Arg194Trp (rs1799782) and ERCC4 Arg415Gln (rs1800067) were significantly associated with BBD [HR, 1.36; 95% confidence interval (95% CI), 1.06-1.74 and HR, 1.39; 95% CI, 1.09-1.76, respectively]. Similar estimates were also observed for each of the BBD criterion used. The BBD association for ERCC4 was even stronger among women with a family history of breast cancer (HR, 2.68; 95% CI, 1.52-4.66; Pinteraction = 0.02). This study suggests that variant alleles in DNA repair genes may modify BBD risk, a potential intermediate marker of breast cancer risk, particularly among high-risk subgroups. (Cancer Epidemiol Biomarkers Prev 2009;18(1):346–50)
Trends in Area-Socioeconomic and Race-Ethnic Disparities in Breast Cancer Incidence, Stage at Diagnosis, Screening, Mortality, and Survival among Women Ages 50 Years and Over (1987-2005)
Authors: Harper Sam , Lynch John , Meersman Stephen C. , Breen Nancy , Davis William W. , Reichman Marsha C. 
Published: January 2009

Abstract
Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death among women in the United States and varies systematically by race-ethnicity and socioeconomic status. Previous research has often focused on disparities between particular groups, but few studies have summarized disparities across multiple subgroups defined by race-ethnic and socioeconomic position.
Methods: Data on breast cancer incidence, stage, mortality, and 5-year cause-specific probability of death (100 − survival) were obtained from the Surveillance, Epidemiology, and End Results program and data on mammography screening from the National Health Interview Survey from 1987 to 2005. We used four area-socioeconomic groups based on the percentage of poverty in the county of residence (&lt;10, 10-15, 15-20, +20%) and five race-ethnic groups (White, Black, Asian, American Indian, and Hispanic). We used summary measures of disparity based on both rate differences and rate ratios.
Results: From 1987 to 2004, area-socioeconomic disparities declined by 20% to 30% for incidence, stage at diagnosis, and 5-year cause-specific probability of death, and by roughly 100% for mortality, whether measured on the absolute or relative scale. In contrast, relative area-socioeconomic disparities in mammography use increased by 161%. Absolute race-ethnic disparities declined across all outcomes, with the largest reduction for mammography (56% decline). Relative race-ethnic disparities for mortality and 5-year cause-specific probability of death increased by 24% and 17%, respectively.
Conclusions: Our analysis suggests progress towards race-ethnic and area-socioeconomic disparity goals for breast cancer, especially when measured on the absolute scale. However, greater progress is needed to address increasing relative socioeconomic disparities in mammography and race-ethnic disparities in mortality and 5-year cause-specific probability of death. (Cancer Epidemiol Biomarkers Prev 2009;18(1):121–31)
Methionine Synthase A2756G Polymorphism Interacts with Alcohol and Folate Intake to Influence the Risk of Colorectal Adenoma
Authors: Yamaji Taiki , Iwasaki Motoki , Sasazuki Shizuka , Sakamoto Hiromi , Yoshida Teruhiko , Tsugane Shoichiro 
Published: January 2009

AbstractGenomic DNA hypomethylation has been associated with colorectal carcinogenesis. Methionine synthase A2756G (MTR A2756G) is a common nonsynonymous polymorphism in the gene that encodes methionine synthase, a key enzyme in the pathway leading to DNA methylation. Several studies, but not all, have reported relatively lower plasma homocysteine among individuals with the AG or GG genotype. Meanwhile, higher plasma homocysteine was associated with genomic DNA hypomethylation in healthy volunteers. We therefore hypothesized that minor allele carriers possess a decreased risk of colorectal adenoma, and examined this hypothesis in a case-control study of colorectal adenoma in Japan involving 723 cases and 670 controls. An unconditional logistic regression model was used to estimate odds ratios (OR) and their 95% confidence intervals (95% CI) for colorectal adenoma after adjustment for potential confounders. Despite the lack of an overall association, we observed a significant interaction between MTR A2756G and alcohol intake (P for interaction = 0.007). Compared with never drinkers with the AA genotype, never drinkers with the AG or GG genotype exhibited a significantly decreased risk (OR, 0.56; 95% CI, 0.34-0.90) whereas heavy drinkers with the same genotypes showed a substantially increased risk (OR, 1.90; 95% CI, 1.04-3.46). In addition, a marginally significant interaction was observed with folate intake (P for interaction = 0.07). The G allele may confer protection against colorectal adenoma in the presence of a considerably good folate status. Our findings add to increasing evidence that DNA methylation plays an important role even at an early stage of colorectal carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2009;18(1):267–74)
Cruciferous Vegetable Consumption and Lung Cancer Risk: A Systematic Review
Authors: Lam Tram Kim , Gallicchio Lisa , Lindsley Kristina , Shiels Meredith , Hammond Edward , Tao Xuguang (Grant) , Chen Liwei , Robinson Karen A. , Caulfield Laura E. , Herman James G. , Guallar Eliseo , Alberg Anthony J. 
Published: January 2009

Abstract
Background: Cruciferous vegetables, rich in isothiocyanates, may protect against lung cancer. Glutathione S-transferases are important in metabolizing isothiocyanates; hence, variants in GST genes may modify the association between cruciferous vegetable intake and lung cancer. We carried out a systematic review to characterize the association between cruciferous vegetable intake and lung cancer risk, with an emphasis on the potential interaction between cruciferous vegetables and GSTM1 and GSTT1 gene variants.
Methods: A search of the epidemiologic literature through December 2007 was conducted using 15 bibliographic databases without language restrictions. Thirty studies on the association between lung cancer and either total cruciferous vegetable consumption (6 cohort and 12 case-control studies) or specific cruciferous vegetables (1 cohort and 11 case-control studies) were included.
Results: The risk for lung cancer among those in the highest category of total cruciferous vegetable intake was 22% lower in case-control studies [random-effects pooled odds ratio, 0.78; 95% confidence interval (95% CI), 0.70-0.88] and 17% lower in cohort studies (pooled relative risk, 0.83; 95% CI, 0.62-1.08) compared with those in the lowest category of intake. The strongest inverse association of total cruciferous vegetable intake with lung cancer risk was seen among individuals with GSTM1 and GSTT1 double null genotypes (odds ratio, 0.41; 95% CI, 0.26-0.65; P for interaction = 0.01).
Conclusions: Epidemiologic evidence suggests that cruciferous vegetable intake may be weakly and inversely associated with lung cancer risk. Because of a gene-diet interaction, the strongest inverse association was among those with homozygous deletion for GSTM1 and GSTT1. (Cancer Epidemiol Biomarkers Prev 2009;18(1):184–95)