bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Meta-analysis of Diabetes Mellitus and the Risk of Prostate Cancer
Authors: Kasper Jocelyn S. , Giovannucci Edward 
Published: November 2006

AbstractBackground: Studies investigating the association between diabetes mellitus and prostate cancer have reported inconsistent findings. We examined this association by conducting a detailed meta-analysis of the studies published on the subject.Methods: MEDLINE and EMBASE databases and bibliographies of retrieved articles were searched. Studies investigating the relationship between diabetes mellitus and prostate cancer were included in the meta-analysis. Potential sources of heterogeneity between studies were explored and publication bias was evaluated. Pooled relative risk (RR) was calculated using the random-effects model. Numerous relevant subgroup analyses were also done.Results: We included 19 studies, published between 1971 and 2005, in the meta-analysis and found an inverse association between diabetes mellitus and prostate cancer [RR, 0.84, 95% confidence interval (CI), 0.76-0.93, P for heterogeneity ≤ 0.01]. For cohort studies alone, the RR was 0.81 (95% CI, 0.71-0.92, P for heterogeneity ≤ 0.01) and for case-control studies alone, the RR was 0.89 (95% CI, 0.72-1.11, P for heterogeneity = 0.02). The significant heterogeneity was mitigated in some of the subgroup analyses. For studies conducted before prostate-specific antigen screening was introduced as a common procedure, the RR was 0.94 (95% CI, 0.85-1.03, P for heterogeneity = 0.15), and for studies conducted after this time, the RR was 0.73 (95% CI, 0.64-0.83, P for heterogeneity = 0.10). For studies that adjusted for three or more potential confounders, the RR was 0.74 (95% CI, 0.65-0.85, P for heterogeneity = 0.06) and for studies that adjusted for less than three potential confounders, the RR was 0.93 (95% CI, 0.86-1.02, P for heterogeneity = 0.18).Conclusion: This study suggests an inverse relationship between diabetes and prostate cancer. Potential biological mechanisms underlying this association, as well as possible biases, are discussed. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2056–62)
The Epidemiology of Second Primary Cancers
Authors: Travis Lois B. 
Published: November 2006

Abstract
Background: Due to improvements in early detection, supportive care, and treatment, the number of cancer survivors in the United States has tripled since 1971 and is growing by 2% each year. In 2001, there were ∼10 million cancer survivors, representing 3.5% of the population. As survival after a diagnosis of cancer improves, quantification of the late effects of cancer and its therapy become critical. One of the most serious events experienced by cancer survivors is the diagnosis of a new cancer. Second- or higher-order cancers now account for ∼16% of incident cancers reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Subsequent neoplasms may not necessarily be attributable to prior cancer treatment but may also reflect the effect of shared etiologic factors, environmental exposures, host characteristics, and combinations of influences, including gene-environment and gene-gene interactions.
Methods/Results: This review will focus on selected highlights and recent findings in treatment-associated malignancies, with an emphasis on survivors of adult cancer. Current study methods will also be summarized.
Conclusions: Important opportunities for future research include the prospective identification of patient subgroups that might be at heightened susceptibility of developing therapy-associated second cancers to modify planned treatments or select alternative management strategies. For the burgeoning population of cancer survivors treated successfully with past regimens, including those therapies that have been subsequently refined, continued quantification of late effects, including second cancers, remains highly relevant in terms of raising clinician and patient awareness, for informed counseling, and for the development of risk-adapted long-term management strategies. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2020–6)
Chemoprevention of Second Cancers
Authors: Mayne Susan T. , Cartmel Brenda 
Published: November 2006

Abstract
Background: “Second cancers” can be thought of in two general categories: (a) those occurring as a consequence of cancer treatment and (b) primary cancers that are thought to develop largely as a consequence of prior lifestyle habits (e.g., chronic smoking, drinking, sun exposures), genetic susceptibility, or interactions of the two. Because there has been limited work on chemoprevention of treatment-related secondary cancers, this minireview will focus on chemoprevention of second cancers with lifestyle/genetic origins.
Methods/Results: Trials aimed at preventing second cancers in patients with tobacco-related cancers (head and neck, lung), skin cancers, breast cancer, and colorectal adenomatous polyps have been completed with some success. However, one finding that has emerged is that, across several cancer sites, subgroups are found with differential response to the chemopreventive agent. For example, smoking status, alcohol consumption, nutritional status, and host tumor characteristics seem to modify chemopreventive efficacy. Stratum-specific (subgroup) findings may occur by chance, requiring a need for supportive evidence from observational epidemiologic studies of the agent (where available), mechanistic studies, or results of other related trials.
Conclusions: Although chemoprevention of second cancers has been realized, it has become increasingly apparent that not all benefit equally. The finding of subgroup effects in completed trials results in the need to consider such subgroup effects in the design of future trials, by either restricting enrollment to particular subgroups (e.g., never or former smokers), or by increasing sample size requirements to allow for variation in response in subgroups in a statistically powerful way. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2033–7)
Higher Methylation Levels in Gastric Mucosae Significantly Correlate with Higher Risk of Gastric Cancers
Authors: Nakajima Takeshi , Maekita Takao , Oda Ichiro , Gotoda Takuji , Yamamoto Seiichiro , Umemura Satoshi , Ichinose Masao , Sugimura Takashi , Ushijima Toshikazu , Saito Daizo 
Published: November 2006

Abstract
Background: Helicobacter pylori infection potently induces methylation of CpG islands in gastric mucosae, which is considered to decrease to a certain level after active H. pylori infection discontinues. Noncancerous gastric mucosae of H. pylori–negative cases with a gastric cancer had higher methylation levels than those of H. pylori–negative healthy individuals. Here, using cases with multiple gastric cancers, we analyzed whether the higher methylation levels correlated with the higher risk of gastric cancers.
Methods: Twenty-six healthy volunteers (HV), 30 cases with a single well-differentiated gastric cancer (S cases), and 32 cases with multiple well-differentiated gastric cancers (M cases) were recruited. H. pylori infection status was analyzed by the culture method. Methylation levels were quantified by real-time methylation-specific PCR of seven CpG islands.
Results: In H. pylori–negative individuals, significant increasing trends were present in the order of HV, S cases, and M cases for FLNc and HAND1 methylation levels (P &lt; 0.01, Spearman's rank-order test). Furthermore, the FLNc methylation level of M cases was significantly higher than that of S cases (P &lt; 0.01, t test). Even adjusted by the extent of gastric atrophy, the FLNc methylation level retained a significant increasing trend (P = 0.03). In contrast, methylation levels in H. pylori–positive individuals were increased to various degrees in all the three groups.
Conclusions: In H. pylori–negative individuals, methylation levels in gastric mucosae significantly increased in cases with a single gastric cancer and more in cases with multiple gastric cancers. Quantitative analysis of methylation levels is a promising risk marker for gastric cancers. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2317–21)
Interleukin-6-Related Genotypes, Body Mass Index, and Risk of Multiple Myeloma and Plasmacytoma
Authors: Cozen Wendy , Gebregziabher Mulugeta , Conti David V. , Van Den Berg David J. , Coetzee Gerhard A. , Wang Sophia S. , Rothman Nathaniel , Bernstein Leslie , Hartge Patricia , Morhbacher Ann , Coetzee Simon G. , Salam Muhammad T. , Wang Wei , Zadnick John , Ingles Sue A. 
Published: November 2006

AbstractInterleukin-6 (IL-6) promotes normal plasma cell development and proliferation of myeloma cells in culture. We evaluated IL-6 genotypes and body mass index (BMI) in a case-control study of multiple myeloma and plasmacytoma. DNA samples and questionnaires were obtained from incident cases of multiple myeloma (n = 134) and plasmacytoma (n = 16; plasma cell neoplasms) ascertained from the Los Angeles County population-based cancer registry and from siblings or cousins of cases (family controls, n = 112) and population controls (n = 126). Genotypes evaluated included IL-6 promoter gene single nucleotide polymorphisms (SNP) at positions −174, −572, and −597; one variable number of tandem repeats (−373 AnTn); and one SNP in the IL-6 receptor (IL-6rα) gene at position −358. The variant allele of the IL-6 promoter SNP −572 was associated with a roughly 2-fold increased risk of plasma cell neoplasms when cases were compared with family [odds ratio (OR), 1.8; 95% confidence interval (95% CI), 0.7-4.7] or population controls (OR, 2.4; 95% CI, 1.2-4.7). The −373 9A/9A genotype was associated with a decreased risk compared with the most common genotype (OR for cases versus family controls, 0.4; 95% CI, 0.1-1.7; OR for cases versus population controls, 0.3; 95% CI, 0.1-0.9). No other SNPs were associated with risk. Obesity (BMI ≥ 30 kg/m2) increased risk nonsignificantly by 40% and 80% when cases were compared with family controls or population controls, respectively, relative to persons with a BMI of &lt;25 kg/m2. These results suggest that IL-6 promoter genotypes may be associated with increased risk of plasma cell neoplasms. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2285–91)
Genetic Variation in the Nucleotide Excision Repair Pathway and Colorectal Cancer Risk
Authors: Berndt Sonja I. , Platz Elizabeth A. , Fallin M. Daniele , Thuita Lucy W. , Hoffman Sandra C. , Helzlsouer Kathy J. 
Published: November 2006

Abstract
Nucleotide excision repair (NER) enzymes are critical for the removal of bulky DNA adducts caused by environmental carcinogens, such as heterocyclic amines and polycyclic aromatic hydrocarbons, which are found in two putative risk factors for colorectal cancer, tobacco smoke and meat cooked at high temperature. To examine the association between common genetic variants in NER genes and the risk of colorectal cancer, we conducted a case-cohort study within the CLUE II cohort. Twenty-two single nucleotide polymorphisms in 11 NER genes were genotyped in 250 colorectal cancer cases and a subcohort of 2,224 participants. Incidence rate ratios (RR) and 95% confidence intervals (95% CI) were estimated using a modified Cox regression model and robust variance estimate. The ERCC6 1213G variant, which is thought to reduce NER capacity, was associated with an increased risk of colorectal cancer compared with the homozygous wild type (RR, 1.36; 95% CI, 1.00-1.86 and RR, 2.64; 95% CI, 1.53-4.58 for the RG and GG genotypes respectively with Ptrend = 0.0006). Having at least one XPC 492H allele was also associated with an increased risk of colorectal cancer (RR, 1.75; 95% CI, 1.20-2.57). When the combined effects of ERCC6 R1213G and XPC R492H were examined, the risk of colorectal cancer significantly increased with increasing number of variant alleles (Ptrend = 0.00003). Our study suggests that genetic polymorphisms in the NER genes, ERCC6 and XPC, may be associated with an increased risk of colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2263–9)
Genetic Polymorphisms of the CYP19A1 Gene and Breast Cancer Survival
Authors: Long Ji-Rong , Kataoka Nobuhiko , Shu Xiao-Ou , Wen Wanqing , Gao Yu-Tang , Cai Qiuyin , Zheng Wei 
Published: November 2006

Abstract
The CYP19A1 protein (aromatase) plays a critical role in estrogen biosynthesis and thus may be related to the progression of breast cancer. We examined the association between CYP19A1 genetic polymorphisms and breast cancer survival in a cohort of 1,136 patients who were recruited as part of a population-based case-control study in Shanghai, China from 1996 to 1998 and who has donated a DNA sample to the study. Patients were followed for cancer recurrence and mortality through July 2005. Nineteen haplotype tagging single-nucleotide polymorphisms (SNP) in the CYP19A1 gene were evaluated. For each of the five SNPs located in haplotype block 2, patients homozygous for the minor alleles had a reduced 5-year disease-free survival rate compared with those carrying the major allele. The age-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were 1.5 (1.1-2.1), 2.1 (1.2-3.6), 1.5 (1.1-2.0), 1.4 (1.0-2.0), and 1.4 (1.0-2.0) for hCV1664178, rs12900137, rs730154, rs936306, and rs1902586, respectively. Haplotype analyses showed that the haplotype CCCTA (all minor alleles of the five SNPs in block 2) was associated with decreased disease-free survival (HR, 1.9; 95% CI, 1.1-3.3). The nonsynonymous SNP, rs700519 (Arg264Cys), located in haplotype block 4, was also associated with breast cancer survival. The age-adjusted HR for the Cys/Cys (T/T) genotype was 2.2 (95% CI, 1.2-4.1) for overall survival and 2.1 (95% CI, 1.1-3.9) for disease-free survival, compared with those carrying the Arg (C) allele. These results suggest that polymorphisms in the CYP19A1 gene may have effects on breast cancer prognosis. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2115–22)
Physical Activity and Risk of Endometrial Cancer: A Population-Based Prospective Cohort Study
Authors: Friberg Emilie , Mantzoros Christos S. , Wolk Alicja 
Published: November 2006

Abstract
Physical activity is involved in the regulation of metabolic and hormonal pathways and is one of the factors important for the maintenance of body weight; obesity is a risk factor for endometrial cancer. A connection between physical activity and endometrial cancer risk through hormonal mechanisms, possibly mediated by body weight, is biologically plausible. Only one study has investigated total physical activity, and no previous study has examined leisure time inactivity directly. We investigated the association of total physical activity and different types of physical activity with risk of endometrial cancer in the Swedish Mammography Cohort, a population-based prospective cohort, including 33,723 women and 199 endometrial cancer cases. After adjustments for potential confounders (age, body mass index, parity, history of diabetes, total fruit and vegetable intake, and education), the relative risks for endometrial cancer for the second to fourth quartile of total physical activity compared with the lowest one were 0.80 [95% confidence interval (95% CI), 0.54-1.18], 0.87 (95% CI, 0.59-1.28), and 0.79 (95% CI, 0.53-1.17). High leisure time inactivity (watching TV/sitting ≥5 hours daily) compared with low was associated with increased risk of endometrial cancer (relative risk, 1.66; 95% CI, 1.05-2.61). The associations were not modified by body mass index. Findings from this study suggest that total physical activity is weakly inversely associated with endometrial cancer risk and that leisure time inactivity is statistically significantly associated with increased risk for endometrial cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2136–40)
Mammographic Breast Density, Dense Area, and Breast Area Differences by Phase in the Menstrual Cycle
Authors: Buist Diana S.M. , Aiello Erin J. , Miglioretti Diana L. , White Emily 
Published: November 2006

Abstract
Background: Mammographic breast density may be greater in the luteal phase (days 15-30) than the follicular phase (days 1-14) of the menstrual cycle; this may have implications for when mammography screening should occur.
Objective: Examine whether percent breast density, breast area, or dense area differ by menstrual phase.
Methods: We identified 204 premenopausal women with regular periods who were &lt;55 years (mean = 45.0 years) and had two screening mammograms within 9 to 18 months, with one screening between days 9 and 14, and one screening between days 22 and 35 of the menstrual cycle. We measured percent breast density, breast area, and dense area using the Cumulus software. We used linear regression to test for differences in breast density, breast area, and dense area from follicular to luteal phase, adjusting for change in weight and time between exams.
Results: The mean (SD) percent breast density was 35.8% (21.3) in the follicular phase and 36.7% (21.3) in the luteal phase. Multivariable analyses showed small but not statistically significant increases in percent density [1.1%; 95% confidence interval (95% CI), −0.2% to 2.3%] and breast area (16.7 cm2; 95% CI, −2.8 to 36.2) and a statistically significant increase in dense area (13.1 cm2; 95% CI, 0.1-26.1) in the luteal compared with the follicular phase.
Conclusions: Breast density, breast area, and dense area have small, but probably not clinically meaningful, increases in the luteal phase of the menstrual cycle. However, there are other factors that may differ by menstrual cycle phase that we were unable to assess (e.g., breast compression), which may ultimately influence mammographic sensitivity by menstrual cycle phase. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2303–6)
The Human Leukocyte Antigen Class I Region Is Associated with EBV-Positive Hodgkin's Lymphoma: HLA-A and HLA Complex Group 9 Are Putative Candidate Genes
Authors: Niens Marijke , van den Berg Anke , Diepstra Arjan , Nolte Ilja M. , van der Steege Gerrit , Gallagher Alice , Taylor G. Malcolm , Jarrett Ruth F. , Poppema Sibrand , te Meerman Gerard J. 
Published: November 2006

Abstract
Various studies have indicated that the human leukocyte antigen (HLA) region is associated with Hodgkin's lymphoma. We recently showed a specific association of the HLA class I region with EBV-positive Hodgkin's lymphoma cases. One haplotype of two consecutive microsatellite markers (D6S265 and D6S510) was overrepresented in the patient group, whereas another haplotype was underrepresented. Here, we did fine mapping of this region of ∼400 kb as a next step to find the causative single-nucleotide polymorphism(s) (SNP). To select candidate SNPs for screening the total study population, several known SNPs were determined by sequencing two individuals homozygous for either of the above-mentioned associated haplotypes. Seven SNPs displayed different alleles in these two individuals and were therefore analyzed in the total study population, including 238 Hodgkin's lymphoma patients and 365 family-based controls. All seven SNPs showed significant association with the EBV-positive patient group. Two of these SNPs were analyzed in a Scottish Hodgkin's lymphoma population and revealed significant associations as well. The associated SNPs are located nearby two putative candidate genes: HLA-A and HLA complex group 9. HLA-A represents the most interesting target because of its consistent expression in EBV-positive Hodgkin's lymphoma cases and its ability to present EBV-derived peptides to cytotoxic T cells. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2280–4)
Glutathione S-Transferase Polymorphisms and the Synergy of Alcohol and Tobacco in Oral, Pharyngeal, and Laryngeal Carcinoma
Authors: Peters Edward S. , McClean Michael D. , Marsit Carmen J. , Luckett Brian , Kelsey Karl T. 
Published: November 2006

Abstract
Investigations of the ability of polymorphisms in the GSTM1, GSTT1, and GSTP1 genes to alter susceptibility to head and neck squamous cell carcinoma (HNSCC) have examined gene-environment interaction in their detoxification of tobacco-associated carcinogens. Little work has been done to ask if these variant genes also modify the interaction of tobacco and alcohol in the development of HNSCC. To test this hypothesis, we conducted a case-control study, enrolling 692 incident cases of HNSCC and 753 population controls. Information about lifetime tobacco and alcohol use was ascertained through questionnaires, and genotypes for GSTM1, GSTT1, and GSTP1 were determined from constitutional DNA. Genotype frequencies were compared among cases and controls, and the association between genotypes and tobacco use was evaluated on cancer risk through logistic regression. Deletion of GSTM1 was associated with an increased risk for HNSCC [odds ratio (OR), 1.3; 95% confidence interval (95% CI), 1.0-1.6]. GSTT1 deletion was associated with a slight decreased HNSCC risk (OR, 0.8; 95% CI, 0.6-1.0). Among those with GSTM1 present, the OR of cancer for heavy smoking was 2.6 (95% CI, 1.6-4.3) compared with 4.2 for those with the GSTM1 deleted (95% CI, 2.6-6.7). The combination of consuming 10 to 20 alcohol drinks weekly and smoking &gt;45 pack-years was associated with a 13-fold elevated risk (OR, 12.6; 95% CI, 4.0-40.2) among the GSTM1 deleted subjects compared with an OR of 3.6 (95% CI, 1.5-8.7) among the GSTM1 present individuals. These data (showing that the GSTM1 deletion affects on the tobacco and alcohol synergy) suggest that the interaction of these carcinogens is, at least in part, driven by alcohol, enhancing the carcinogenic action of tobacco smoke. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2196–202)
APC E1317Q Is Not Associated with Colorectal Cancer in a Population-Based Case-Control Study in Northern Israel
Authors: Rozek Laura S. , Rennert Gad , Gruber Stephen B. 
Published: November 2006

Abstract
A variant in the adenomatous polyposis coli gene, APC E1317Q, has been inconsistently associated with risk of colorectal cancer. We used data collected as a part of the Molecular Epidemiology of Colorectal Cancer study, a population-based study of colorectal cancer in northern Israel (1,834 matched cases and controls), to evaluate the relationship between this variant and risk of sporadic colorectal cancer. There was no association between E1317Q and colorectal cancer [odds ratio (OR), 1.15; 95% CI, 0.65-2.02]. When the control sample was restricted to polyp-free controls, the OR was 0.87 (95% CI, 0.36-2.14), indicating that this result is unlikely to be due to nondifferential misclassification due to undiagnosed polyps. A meta-analysis including these data and prior published reports found a nonsignificant summary OR nearly identical to the association reported here in the Molecular Epidemiology of Colorectal Cancer case-control study. Although there are previously published reports addressing this question, due to the low frequency of the variant, many of these studies lack the power to estimate the risk in a meaningful way. Given the substantial size of our study and the consistency of our findings with the results of our meta-analyses, we conclude that it is unlikely that APC E1317Q is associated with a clinically meaningful risk of colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2325–7)