bluuebunny/crossref_metadata_2025_split huggingface dataset:
Height, Age at Menarche, and Risk of Epithelial Ovarian Cancer
Authors: Jordan Susan J. , Webb Penelope M. , Green Adèle C. 
Published: September 2005

Abstract
Objective: We hypothesized that the hormonal changes of adolescence influence ovarian cancer risk particularly in younger women. We investigated this possibility by examining the relationship between ovarian cancer and adult height and age at menarche as both factors reflect pubertal hormonal levels.
Methods: Participants were a population-based sample of women with incident ovarian cancer (n = 794) and control women randomly selected from the Australian Electoral Roll (n = 855). The women provided comprehensive reproductive and lifestyle data during a standard interview.
Results: Although neither height nor age at menarche was significantly related to the risk of ovarian cancer overall, increasing height was associated with increasing risk of the subgroup of mucinous borderline ovarian cancer (odds ratio, 5.3; 95% confidence interval, 1.5-19.1 for women ≥175 cm compared with women &lt;160 cm, Ptrend = 0.02). Similarly, later age at menarche was associated with increasing risk of mucinous borderline cancers (odds ratio, 3.8; 95% confidence interval, 1.3-11.4 for those with age at menarche ≥14 years compared with those &lt;12 years, Ptrend = 0.003). Women with mucinous borderline cancers were significantly younger than the women diagnosed with invasive cancers (mean 44 versus 57 years; P &lt; 0.0001).
Conclusions: Development of mucinous borderline ovarian cancers, predominantly diagnosed in women ages under 50 years, seems to be associated with age at menarche and attained adult height. These results are consistent with our original hypothesis that pubertal levels of reproductive hormones and insulin-like growth factor-I influence ovarian cancer risk in younger women.
Genetic Polymorphisms of GlutathioneS-Transferases and the Risk of Adult Brain Tumors: A Meta-analysis
Authors: Lai Rose , Crevier Louis , Thabane Lehana 
Published: September 2005

AbstractBackground: Studies investigating the association between genetic polymorphisms of glutathione S-transferases (GST) and risk of adult brain tumors have reported conflicting results. The rationale of this meta-analysis was to determine whether GST variants increase the susceptibility of adult brain tumors by pooling data.Methods: Two investigators independently searched the HuGENet database, MEDLINE, EMBASE, conference articles, and manually reviewed bibliographies of retrieved articles. Papers were included if they were observational studies investigating the influence of GSTM1, GSTT1, GSTP1 I105V, or GSTP1 A114V on the development of adult brain cancers. Potential sources of heterogeneity between studies were explored in a meta-regression.Results: We identified eight eligible studies, which included 1,630 cases of glioma, 245 cases of meningioma, and 7,151 controls. Using the random effects model, there was no association between any of the GST variants and the risk of glioma [overall odds ratio (OR), 1.08; 95% confidence interval (95% CI), 0.95-1.22]. Subgroup analyses also showed no relationship between GST variants and histopathologic groups; the overall ORs were 1.13 (95% CI, 0.88-1.43) for high-grade glioma and 1.08 (95% CI, 0.76-1.55) for low-grade glioma. A random effects meta-regression suggested that the use of in-hospital controls produced larger effect estimates in glioma than the use of population controls (overall OR, 1.30; 95% CI, 1.03-1.65). The T1 null genotype was significantly associated with a risk of meningioma (OR, 1.95; 95% CI, 1.02-3.76), but the M1 variant was not.Conclusion: This study did not suggest any relationship between GST variants and risks of glioma; the T1 null genotype may influence the susceptibility of meningioma, but larger studies are needed to substantiate this relationship.
Fruits, Vegetables, and hMLH1 Protein–Deficient and –Proficient Colon Cancer: The Netherlands Cohort Study
Authors: Wark Petra A. , Weijenberg Matty P. , van 't Veer Pieter , van Wijhe Gerda , Lüchtenborg Margreet , van Muijen Goos N.P. , de Goeij Anton F.P.M. , Goldbohm R. Alexandra , van den Brandt Piet A. 
Published: September 2005

Abstract
Background: Clinical and pathologic differences exist between colon carcinomas deficient and proficient in the mismatch repair protein hMLH1. Animal and in vitro studies suggest that fruits, vegetables, folate, and antioxidants are associated with colonic expression of mismatch repair genes.
Methods: Associations between consumption of fruits and vegetables and hMLH1 protein–deficient and –proficient colon cancer were evaluated in the Netherlands Cohort Study on diet and cancer using a case-cohort approach. A self-administered food frequency questionnaire was completed, in 1986, by 120,852 individuals ages 55 to 69 years. Using immunohistochemistry, hMLH1 protein expression was assessed in colon cancer tissue obtained from 441 patients who were identified over 7.3 years of follow-up excluding the initial 2.3 years. Incidence rate ratios (RR) were estimated for hMLH1 protein–deficient and –proficient colon cancer.
Results: hMLH1 protein expression was absent in 54 tumors (12.2%) and present in 387 tumors. Fruit consumption was associated with hMLH1 protein–deficient colon cancer [highest versus lowest tertile, RR, 0.46; 95% confidence interval (95% CI), 0.23-0.90; Ptrend = 0.029] but not with hMLH1 protein–proficient tumors (highest versus lowest tertile, RR, 1.03; 95% CI, 0.78-1.35; Ptrend = 0.81). Total consumption of vegetables was not associated with either type of tumor (hMLH1 protein deficient: RR, 0.86; 95% CI, 0.45-1.65; Ptrend = 0.67; hMLH1 protein proficient: RR, 0.94; 95% CI, 0.72-1.23; Ptrend = 0.72). No associations were observed for folate, fiber, antioxidants, or subgroups of vegetables.
Conclusion: These analyses indicate that an inverse association between consumption of fruits and colon cancer may be confined to the subgroup of tumors with a deficient mismatch repair system.
Sulindac Inhibits β-Catenin Expression in Normal-Appearing Colon of Hereditary Nonpolyposis Colorectal Cancer and Familial Adenomatous Polyposis Patients
Authors: Koornstra Jan J. , Rijcken Fleur E.M. , Oldenhuis Corina N.A.M. , Zwart Nynke , van der Sluis Tineke , Hollema Harry , deVries Elisabeth G.E. , Keller Josbert J. , Offerhaus Johan A. , Giardiello Francis M. , Kleibeuker Jan H. 
Published: September 2005

Abstract
Sulindac reduces colorectal cancer risk in genetically susceptible humans and animals. The molecular mechanisms underlying these effects are incompletely understood. Many studies suggest an important role for induction of apoptosis involving the mitochondrial pathway and the death receptor pathway. Alternatively, mechanisms involving the APC-β-catenin-Wnt pathway have been suggested, possibly mediated by p21. We determined the effects of sulindac on apoptosis and expression of death receptor (DR)-4 and DR5, β-catenin, and p21 in normal-appearing colorectal epithelium. Biopsies were obtained before and after sulindac treatment during two chemoprevention studies. Patients (n = 18) with hereditary nonpolyposis colorectal cancer (HNPCC) received 150 mg sulindac bd for 4 weeks in a placebo-controlled crossover design. Patients (n = 6) with familial adenomatous polyposis (FAP) received 150 mg sulindac bd for 6 months. Apoptosis was assessed by M30 staining and expression patterns of DR4, DR5, β-catenin, and p21 were studied immunohistochemically. In HNPCC patients, apoptotic indices were similar following placebo and sulindac. Also in FAP patients, apoptotic indices were not different after sulindac compared with pretreatment values. Expression of DR4 and DR5 was observed in all samples with no consistent differences between placebo/baseline and sulindac. Intensity of membranous β-catenin staining was lower in HNPCC samples following sulindac compared with placebo (P &lt; 0.001). Similar results were obtained in FAP samples (P &lt; 0.01). p21 expressions before and after sulindac treatment were similar in both patient groups. In conclusion, sulindac inhibits β-catenin expression in normal colorectal epithelium from HNPCC and FAP patients without affecting apoptotic indices and DR4, DR5, and p21 expression.
Differences in Survival by Histologic Type of Pancreatic Cancer
Authors: Fesinmeyer Megan Dann , Austin Melissa A. , Li Christopher I. , De Roos Anneclaire J. , Bowen Deborah J. 
Published: September 2005

Abstract
Objective: Although pancreatic cancer has an extremely high case fatality rate, little is known about differences in mortality by histologic types. We examined median survival and risk of mortality for endocrine pancreatic tumors and two types of exocrine tumors, adenocarcinomas, and mucinous tumors.
Method: This analysis included 35,276 pancreatic cancer cases reported to the nine population-based cancer registries participating in the Surveillance, Epidemiology, and End Results program from 1973 to 2000. Survival among cases with pancreatic adenocarcinomas, mucinous tumors, and endocrine tumors were compared using Kaplan-Meier plots. Comparative risks of mortality were evaluated using multivariate adjusted Cox regression models.
Results: Endocrine pancreatic cancer cases had a median survival of 27 months compared with a median survival of 4 months for adenocarcinoma and mucinous tumor cases. Compared with adenocarcinoma cases, endocrine tumor cases had a 0.28-fold lower risk of mortality [95% confidence interval (95% CI), 0.26-0.30], and mucinous tumor cases had a 0.88-fold lower risk (95% CI, 0.84-0.91). These results were similar for men and women. Within histologic types, advanced tumor stage, older diagnosis age, surgery, and Black race were associated with increased risks of mortality, whereas female sex and more recent year of diagnosis were associated with decreased risks.
Conclusion: This study confirms the clinical observation that patients with endocrine pancreatic cancer survive longer than patients with exocrine tumors. A better understanding of these differences could contribute to identifying the underlying causes of pancreatic cancer and to improving survival rates across all histologic types.
Maternal Hormone Levels and Risk of Cryptorchism among Populations at High and Low Risk of Testicular Germ Cell Tumors
Authors: McGlynn Katherine A. , Graubard Barry I. , Nam Jun-Mo , Stanczyk Frank Z. , Longnecker Matthew P. , Klebanoff Mark A. 
Published: September 2005

Abstract
Cryptorchism is one of the few well-described risk factors for testicular cancer. It has been suggested that both conditions are related to increased in utero estrogen exposure. The evidence supporting the “estrogen hypothesis” has been inconsistent, however. An alternative hypothesis suggests that higher in utero androgen exposure may protect against the development of cryptorchism and testicular cancer. In order to examine both hypotheses, we studied maternal hormone levels in two populations at diverse risks of testicular cancer; Black Americans (low-risk) and White Americans (high-risk). The study population of 200 mothers of cryptorchid sons and 200 mothers of noncryptorchid sons was nested within the Collaborative Perinatal Project, a cohort study of pregnant women and their children. Third trimester serum levels of estradiol (total, free, bioavailable), estriol, testosterone (total, free, bioavailable), sex hormone–binding globulin, α-fetoprotein, and the ratios of estradiols to testosterones were compared between the case and control mothers. The results found no significant differences in the levels of testosterone (total, free, bioavailable), α-fetoprotein, sex hormone–binding globulin, or in the ratios of estrogens to androgens. Total estradiol, however, was significantly lower in the cases versus the controls (P = 0.03) among all mothers and, separately, among White mothers (P = 0.05). Similarly, estriol was significantly lower among all cases (P = 0.05) and among White cases (P = 0.05). These results do not support either the estrogen or the androgen hypothesis. Rather, lower estrogens in case mothers may indicate that a placental defect increases the risk of cryptorchism and, possibly, testicular cancer.
Social and Behavioral Correlates of Cigarette Smoking among Mid-Atlantic Latino Primary Care Patients
Authors: Cox Lisa Sanderson , Feng Shibao , Cañar Janet , Ford Maureen McGlinchey , Tercyak Kenneth P. 
Published: September 2005

Abstract
Tobacco use is the leading preventable cause of death for the U.S. Hispanic population. The goal of this study was to identify social and behavioral correlates of smoking behavior among urban, multiethnic Latino primary care patients seen in community clinics. Spanish-language interviews were completed with 141 current smokers and 158 former and nonsmokers. Twenty countries of origin were represented. Eighty-three percent of participants were from Central or South America and 71% spoke primarily Spanish. Current smokers were more likely than nonsmokers or former smokers to originate from South America (38% versus 26%) and to be single (63% versus 42%). Current smokers also were more likely to use alcohol on a regular basis (59% versus 31%) and to experience daily symptoms of depression (29% versus 19%). Logistic regression analysis suggested a moderating effect of depression on the relationship between alcohol use and smoking, such that current users of alcohol who reported depression were more likely to smoke (82%) than were current users of alcohol who did not report depression (56%). As both social and behavioral factors were uniquely associated with smoking, country of origin, marital status, and comorbid alcohol use and depression should be considered in designing and implementing tobacco control interventions targeted to this community.
Insulin-Like Growth Factor Pathway Polymorphisms Associated with Body Size in Hispanic and Non-Hispanic White Women
Authors: Sweeney Carol , Murtaugh Maureen A. , Baumgartner Kathy B. , Byers Tim , Giuliano Anna R. , Herrick Jennifer S. , Wolff Roger , Caan Bette J. , Slattery Martha L. 
Published: September 2005

AbstractPolymorphisms affecting insulin-like growth factors (IGF), their binding proteins (IGFBP), insulin receptor substrates (IRS), and other IGF regulatory molecules may affect growth, obesity, and obesity-related diseases, including cancer. The objective of this study was to better describe the associations between several IGF pathway variants and body size. Hispanic (n = 462) and non-Hispanic White (n = 1,702) women were recruited as controls in collaborative population-based case-control studies in Arizona, New Mexico, Colorado, Utah, and California. Body size measurements were taken by trained interviewers; genotypes were determined for the IGF1 CA repeat, the IGFBP3 −202 C &gt; A substitution, the IRS1 G972R and IRS2 G1057D substitutions, and the vitamin D receptor (VDR) BsmI and FokI polymorphisms. Two associations were observed that were consistent in both Hispanics and non-Hispanic Whites: IGF1 CA repeat alleles of length other than 19 were associated with higher mean waist-to-hip ratios (WHR), P = 0.01, and women who carried an IGFBP3 A allele, compared with women with the CC genotype, more often reported high birthweight (odds ratio, 1.9; 95% confidence interval, 1.1-3.2). We observed trends for associations between IGFBP3 A allele and taller height, IRS1R allele, and smaller WHR, and VDR FokI ff genotype and larger WHR; each of these trends was present in only one ethnic group, and heterogeneity of effect by ethnicity was detected. These results provide evidence that IGF pathway polymorphisms have functional effects on growth and central obesity and indicate that genotype-phenotype relationships are ethnic specific.
Identifying Susceptibility Genes for Prostate Cancer—A Family-Based Association Study of Polymorphisms in CYP17, CYP19, CYP11A1, and LH-β
Authors: Douglas Julie A. , Zuhlke Kimberly A. , Beebe-Dimmer Jennifer , Levin Albert M. , Gruber Stephen B. , Wood David P. , Cooney Kathleen A. 
Published: September 2005

Abstract
Polymorphisms in genes that code for enzymes or hormones involved in the synthesis and metabolism of androgens are compelling biological candidates for prostate cancer. Four such genes, CYP17, CYP19, CYP11A1, and LH-β, are involved in the synthesis and conversion of testosterone to dihydrotestosterone and estradiol. In a study of 715 men with and without prostate cancer from 266 familial and early-onset prostate cancer families, we examined the association between prostate cancer susceptibility and common single-nucleotide polymorphisms in each of these four candidate genes. Family-based association tests revealed a significant association between prostate cancer and a common single-nucleotide polymorphism in CYP17 (P = 0.004), with preferential transmission of the minor allele to unaffected men. Conditional logistic regression analysis of 461 discordant sibling pairs from these same families reaffirmed the association between the presence of the minor allele in CYP17 and prostate cancer risk (odds ratio, 0.51; 95% confidence interval, 0.28-0.92). These findings suggest that variation in or around CYP17 predicts susceptibility to prostate cancer. Family-based association tests may be especially valuable in studies of genetic variation and prostate cancer risk because this approach minimizes confounding due to population substructure, which is of particular concern for prostate cancer given the tremendous variation in the worldwide incidence of this disease.
Crypt-Restricted Loss and Decreased Protein Expression of Cytochrome c Oxidase Subunit I as Potential Hypothesis-Driven Biomarkers of Colon Cancer Risk
Authors: Payne Claire M. , Holubec Hana , Bernstein Carol , Bernstein Harris , Dvorak Katerina , Green Sylvan B. , Wilson Megan , Dall'Agnol Monique , Dvorakova Barbora , Warneke James , Garewal Harinder 
Published: September 2005

Abstract
There is an increasing demand for the development of intermediate biomarkers to assess colon cancer risk. We previously determined that a live cell bioassay, which assesses apoptosis resistance in the nonneoplastic colonic mucosa, detects ∼50% of patients with colon cancer. A hypothesis-driven biomarker that reflects apoptosis resistance in routine formalin-fixed, paraffin-embedded tissue would be easier to use. Cytochrome c oxidase is a critical enzyme that controls mitochondrial respiration and is central to apoptosis. We did an immunohistochemical study of cytochrome c oxidase subunit I expression in 46 colonic mucosal samples from 16 patients who had undergone a colonic resection. These included five patients without evidence of colonic neoplasia (three normal and two diverticulitis), three patients with tubulovillous adenomas, and eight patients with colonic adenocarcinomas. Analysis of aberrancies in expression of cytochrome c oxidase subunit I showed that, compared with nonneoplasia, the patients with neoplasia had a higher mean incidence of crypts having decreased expression (1.7 versus 22.8, P = 0.03) and a higher mean incidence having crypt-restricted loss (0.6 versus 3.2, P = 0.06). The percentage with segmented loss was low and was similar in the two groups. Combining these results, the mean % normal (i.e., with none of the three types of abnormality) was 96.7 in nonneoplasia versus only 73.2 in patients with neoplasia (P = 0.02). It should be noted that a defect in cytochrome c oxidase subunit I immunostaining was not detected in all biopsy samples from each patient for whom some abnormality was found, indicating a “patchiness” in the cytochrome c oxidase subunit I field defect. As a result of this “patchiness,” the increased variability in the incidence of crypt-restricted loss of cytochrome c oxidase subunit I expression was a statistically significant feature of the neoplasia group. Crypt-restricted loss of cytochrome c oxidase subunit I has not been previously reported in colonic mucosa and is presumably the result of a crypt-restricted stem cell mutation. Decreased cytochrome c oxidase subunit I expression also significantly correlated with apoptosis resistance, a factor known to contribute to carcinogenesis. The results suggest, however, that aberrant cytochrome c oxidase subunit I expression may be a better biomarker than loss of apoptosis competence for increased colon cancer risk.
Alcohol, ALDH2, and Esophageal Cancer: A Meta-analysis Which Illustrates the Potentials and Limitations of a Mendelian Randomization Approach
Authors: Lewis Sarah J. , Davey Smith George 
Published: September 2005

Abstract
Mendelian randomization, the use of common polymorphisms as surrogates for measuring exposure levels in epidemiologic studies, provides one method of assessing the causal nature of some environmental exposures. This can be illustrated by looking at the association between the ALDH2 polymorphism and esophageal cancer. Alcohol drinking is considered a risk factor for esophageal cancer, and exposure to high levels of acetaldehyde, the principal metabolite of alcohol, may be responsible for the increased cancer risk. The ability to metabolize acetaldehyde is encoded by the ALDH2 gene, which is polymorphic in some populations. The ALDH2*2 allele produces an inactive protein subunit, which is unable to metabolize acetaldehyde. An individual's genotype at this locus may influence their esophageal cancer risk through two mechanisms, first through influencing alcohol intake and second through influencing acetaldehyde levels. We have carried out a meta-analysis of studies looking at the ALDH2 genotype and esophageal cancer and found that risk was reduced among *2*2 homozygotes [odds ratio (OR), 0.36; 95% confidence interval (95% CI), 0.16-0.80] and increased among heterozygotes (OR, 3.19; 95% CI, 1.86-5.47) relative to *1*1 homozygotes. This provides strong evidence that alcohol intake increases the risk of esophageal cancer and individuals whose genotype results in markedly lower intake, because they have an adverse reaction to alcohol are thus protected. This meta-analysis also provides evidence that acetaldehyde plays a carcinogenic role in esophageal cancer. The two different processes operating as a result of the ALDH2 genotype have implications for the interpretation of studies using the Mendelian randomization paradigm.
Familial Lung Cancer and Aggregation of Smoking Habits: A Simulation of the Effect of Shared Environmental Factors on the Familial Risk of Cancer
Authors: Lorenzo Bermejo Justo , Hemminki Kari 
Published: September 2005

Abstract
Background: Tobacco smoking is the principal cause of lung cancer. The risk of lung cancer in the offspring of lung cancer patients is about twice higher than the risk in the general population. The present study investigated the contribution of shared smoking habits to the familial clustering of lung cancer.
Methods: We estimated the relative risk of lung cancer attributable to smoking according to the extent to which smokers transmit their smoking habits to the offspring (heritability of smoking), the prevalence of smoking in the general population, and the risk of lung cancer for smokers compared with nonsmokers.
Findings: The relative risk of lung cancer for the offspring of lung cancer patients attributable to smoking was 1.19 when published data on smoking practice were modeled (i.e., assuming that the heritability of smoking was 0.5, the smoking prevalence 40%, and the odds ratio of lung cancer for smokers versus nonsmokers was 20).
Interpretation: Most familial cases of lung cancer cannot be attributed to shared smoking habits. The example of smoking can be used for other familial cancers, for which no strong environmental risk factors are usually known, to infer the primary role for heritable genes.