bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Statin Use on Breast Density
Authors: Boudreau Denise M. , Rutter Carolyn M. , Buist Diana S.M.
Published: May 2006

Objective: To evaluate if 3-hydroxy-3-methylglutaryl CoA reductase reductase inhibitor use (statins) alters mammography measured breast density.

Methods: Cohort study of women ages 50 to 80 years with two mammography screenings. Changes in BI-RADS breast density between screenings was compared for nonusers, initiators, discontinuers, continuers, and any users of statins.

Results: Statin use was not associated with increases or decreases in breast density compared with nonusers after adjusting for age, body mass index, change in body mass index, hormone therapy use, and time between screenings. Cumulative days of statin use during the year before screening was not associated with changes in breast density in any of the groups of statin users. When hormone therapy users were excluded, any statin use was associated with an increase in breast density compared with nonusers (odds ratio, 1.2; 95% confidence interval, 1.0-1.5).

Conclusions: We found no association between statin use and change in breast density in general, but statin use may be associated with increases in breast density among nonusers of hormone therapy. (Cancer Epidemiol Biomarkers Prev 2006;15(5):1026–9)
Estimating the Effect of Human Base Excision Repair Protein Variants on the Repair of Oxidative DNA Base Damage
Authors: Sokhansanj Bahrad A. , Wilson David M.
Published: May 2006

Epidemiologic studies have revealed a complex association between human genetic variance and cancer risk. Quantitative biological modeling based on experimental data can play a critical role in interpreting the effect of genetic variation on biochemical pathways relevant to cancer development and progression. Defects in human DNA base excision repair (BER) proteins can reduce cellular tolerance to oxidative DNA base damage caused by endogenous and exogenous sources, such as exposure to toxins and ionizing radiation. If not repaired, DNA base damage leads to cell dysfunction and mutagenesis, consequently leading to cancer, disease, and aging. Population screens have identified numerous single-nucleotide polymorphism variants in many BER proteins and some have been purified and found to exhibit mild kinetic defects. Epidemiologic studies have led to conflicting conclusions on the association between single-nucleotide polymorphism variants in BER proteins and cancer risk. Using experimental data for cellular concentration and the kinetics of normal and variant BER proteins, we apply a previously developed and tested human BER pathway model to (i) estimate the effect of mild variants on BER of abasic sites and 8-oxoguanine, a prominent oxidative DNA base modification, (ii) identify ranges of variation associated with substantial BER capacity loss, and (iii) reveal nonintuitive consequences of multiple simultaneous variants. Our findings support previous work suggesting that mild BER variants have a minimal effect on pathway capacity whereas more severe defects and simultaneous variation in several BER proteins can lead to inefficient repair and potentially deleterious consequences of cellular damage. (Cancer Epidemiol Biomarkers Prev 2006;15(5):1000–8)
Difference in the Incidence Trend of Nasopharyngeal and Oropharyngeal Carcinomas in Taiwan: Implication from Age-Period-Cohort Analysis
Authors: Hsu Chiun , Shen Ying-Chun , Cheng Chia-Chi , Hong Ruey-Long , Chang Chee-Jen , Cheng Ann-Lii
Published: May 2006

Lifestyle factors are considered important for the pathogenesis of both nasopharyngeal and oropharyngeal carcinomas. In Taiwan, the incidence of nasopharyngeal carcinoma gradually decreased over the past 20 years, whereas that of oropharyngeal carcinoma increased rapidly. To compare the incidence trends of nasopharyngeal and oropharyngeal carcinomas in Taiwan, the age-period-cohort model was used to analyze epidemiologic data from 1981 to 2000 obtained from the Taiwan Cancer Registry. The calendar time period of 1986 to 1990 and the 1931 to 1940 birth cohort were used as reference groups for estimates of relative risk. For nasopharyngeal carcinoma, the incidence seemed to decrease in most age groups and was more prominent in women (30%) than in men (23%). For oropharyngeal carcinoma, the incidence increased in all age groups and was more prominent in men (391.4%) than in women (59.2%). Cohort effect was found for both nasopharyngeal and oropharyngeal carcinomas. The relative risk of nasopharyngeal carcinoma for the 1971 to 1980 birth cohort was 0.38 for women and 0.68 for men. The relative risk of oropharyngeal carcinoma for the 1971 to 1980 cohort was 45.67 for men and 2.69 for women. Change in lifestyle seemed to be an important factor for the difference in the incidence trend between nasopharyngeal and oropharyngeal carcinomas and between men and women. (Cancer Epidemiol Biomarkers Prev 2006;15(5):856–61)
Human Papillomavirus Testing Following Loop Electrosurgical Excision Procedure Identifies Women at Risk for Posttreatment Cervical Intraepithelial Neoplasia Grade 2 or 3 Disease
Authors: Kreimer Aimée R. , Guido Richard S. , Solomon Diane , Schiffman Mark , Wacholder Sholom , Jeronimo José , Wheeler Cosette M. , Castle Philip E. ,   for the ASCUS-LSIL Triage Study (ALTS) Group
Published: May 2006

Background: Loop electrosurgical excision procedure (LEEP) is the predominant treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN2+) in the United States, yet following treatment ∼10% of women are diagnosed again with CIN2+, necessitating close follow-up of such patients.

Methods: Surveillance strategies using cytology and/or human papillomavirus (HPV) testing were compared among women who underwent LEEP (n = 610) in the Atypical Squamous Cells of Undetermined Significance (ASCUS) Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. Cervical specimens, collected at 6-month visits for 2 years, were used for cytology, Hybrid Capture 2 (HC2) detection of carcinogenic HPVs, and PCR for genotyping of carcinogenic and noncarcinogenic HPV types. At exit, women had colposcopy for safety and disease ascertainment.

Results: At the visit post-LEEP (median time: 4.5 months after LEEP), 36.9% [95% confidence interval (95% CI), 32.7-41.1%] of women were positive for carcinogenic HPV by PCR and 33.7% (95% CI, 29.7-37.9) had ASCUS or more severe (ASCUS+) cytology. The overall 2-year cumulative incidence of histologically confirmed posttreatment CIN2+ was 7.0%; this could be further stratified by the HPV risk category detected at the 6-month visit after LEEP. The 2-year risk associated with HPV16 positivity was 37.0%, significantly higher than for other carcinogenic HPV types (10.8%, P < 0.001), noncarcinogenic types (1.5%, P < 0.001), or testing HPV negative (0%). Post-LEEP cytology (using a positive threshold of ASCUS+) was 78.1% (95% CI, 60.0-90.7%) sensitive for detection of posttreatment CIN2+. By comparison, PCR for carcinogenic HPV and combination testing (using a positive result from carcinogenic HPV testing or cytology as the test threshold with HPV-negative ASCUS not referred) were significantly more sensitive (96.9% for each, P = 0.03); HC2 alone was nonsignificantly more sensitive (90.6%, P = 0.3). Specificity was similar for ASCUS+ cytology (69.1%, 95% CI, 64.6-73.3%) and PCR for carcinogenic HPV (67.1%, P = 0.5), yet was lower for HC2 (63.8%, P = 0.048) and combination testing (62.9%, P = 0.02).

Conclusion: Women who tested positive after LEEP for carcinogenic HPV types, especially HPV16, had high risk of subsequent CIN2+. HPV-based detection methods, alone or in combination with cytology, may be useful to incorporate in post-LEEP management strategies. (Cancer Epidemiol Biomarkers Prev 2006;15(5):908–14)
Reproducibility of Plasma Steroid Hormones, Prolactin, and Insulin-like Growth Factor Levels among Premenopausal Women over a 2- to 3-Year Period
Authors: Missmer Stacey A. , Spiegelman Donna , Bertone-Johnson Elizabeth R. , Barbieri Robert L. , Pollak Michael N. , Hankinson Susan E.
Published: May 2006

Few studies have evaluated whether a single blood hormone measurement, as is available in most epidemiologic studies, sufficiently characterizes a premenopausal woman's long-term hormone levels; there is particular concern whether sex steroid hormones, which fluctuate during the menstrual cycle, are reliable. We conducted a prospective study within the Nurses' Health Study II to examine the reproducibility of plasma estrogens, androgens, progesterone, prolactin, sex hormone binding globulin, insulin-like growth factor–I (IGF-I), and IGF binding protein–3 (IGFBP-3). One blood sample per year over 3 years was collected from 113 premenopausal women during both the follicular and luteal phases of the menstrual cycle. We calculated intraclass correlation coefficients (ICC) across the three samples for all women. Among estrogens, ICCs ranged from 0.38 (estradiol) to 0.60 (estrone sulfate) in the follicular phase and from 0.44 (estrone) to 0.69 (estrone sulfate) in the luteal phase. Among androgens, ICCs ranged from 0.58 (androstenedione) to 0.94 [dehydroepiandrostenedione sulfate (DHEAS)] in the follicular phase and from 0.56 (testosterone) to 0.81 (DHEAS) in the luteal phase. When values were averaged across the follicular and luteal phases, the ICC for prolactin was 0.64 whereas ICCs for IGF-I and IGFBP-3 were 0.86 and 0.82, respectively. The ICC for progesterone in the luteal phase was only 0.29. These data suggest that for androgens, estrone sulfate, prolactin, IGF-I, and IGFBP-3, a single measurement can reliably categorize average levels over at least a 3-year period in premenopausal women. For estrone and estradiol, where ICCs were relatively low, it is important to use reproducibility data such as those to correct for measurement error in epidemiologic studies. (Cancer Epidemiol Biomarkers Prev 2006;15(5):972–8)
Gender-Specific Protective Effect of Hemoglobin on Arsenic-Induced Skin Lesions
Authors: Breton Carrie V. , Houseman E. Andres , Kile Molly L. , Quamruzzaman Quazi , Rahman Mahmuder , Mahiuddin Golam , Christiani David C.
Published: May 2006

Chronic arsenic poisoning remains a public health crisis in Bangladesh. As arsenic has been shown to bind to human hemoglobin (Hb), hematologic mechanisms may play a role in the pathway through which arsenic exerts its toxicity. Two separate studies, a case-control and a cohort, were conducted to investigate the role of Hb in the development of arsenic-induced skin lesions. In the first, conditional logistic regression was used to investigate the effect of Hb on skin lesions among 900 case-control pairs from Pabna, Bangladesh, in which individuals were matched on gender, age, and location. In the second, mixed linear regression models were used to examine the association between toenail arsenic, urinary arsenic, and Hb within a cohort of 184 individuals from 50 families in the same region who did not have arsenic-induced skin lesions. Hb was significantly associated with skin lesions but this association was gender specific. In males, a 40% reduction in the odds of skin lesions occurred for every 1 g/dL increase in Hb (odds ratio, 0.60; 95% confidence interval, 0.49-0.73). No effect was observed for females (odds ratio, 1.16; 95% confidence interval, 0.92-1.46). In the cohort of 184 individuals, no associations between toenail arsenic or urinary arsenic species and Hb levels were observed. Low Hb levels may exacerbate the detrimental health effects of chronic arsenic poisoning. Whereas providing clean water remains the optimal solution to Bangladesh's problem of arsenic poisoning, improving nutrition and reducing iron-deficiency anemia may ameliorate negative health effects, such as skin lesions in individuals who have been exposed. (Cancer Epidemiol Biomarkers Prev 2006;15(5):902–7)
Body Mass Index and Adenocarcinomas of the Esophagus or Gastric Cardia: A Systematic Review and Meta-analysis
Authors: Kubo Ai , Corley Douglas A.
Published: May 2006

Background: The incidence of esophageal adenocarcinoma has increased markedly in recent decades in many countries. Obesity is a potential risk factor, although the results of individual studies differ. We did a systematic review and statistical synthesis of studies that evaluated the association between body mass index (BMI) and the risk of esophageal adenocarcinoma or the adjacent gastric cardia adenocarcinoma.

Methods: We identified potential studies using Medline, the Web of Science database, a manual review of the literature and expert bibliographies. Studies were included if they reported (a) a measure of body mass; (b) the occurrence of esophageal or cardia adenocarcinoma diagnosis; and (c) a relative risk or odds ratio (OR) with confidence intervals (CI) or provided sufficient data to permit their calculation.

Results: We identified 14 studies (2 cohort, 12 case-control; 2,488 esophageal and 2,509 cardia adenocarcinomas). A high BMI (>25) was associated with an increased risk of esophageal adenocarcinoma (males, OR, 2.2; 95% CI, 1.7-2.7; females, OR, 2.0; 95% CI, 1.4-2.9). Higher levels of BMI were associated with increased risk (overweight males, OR, 1.8; 95% CI, 1.5-2.2; obese males, OR, 2.4; 95% CI, 1.9-3.2). The overall associations with cardia cancer were heterogeneous, although stratification by study location provided homogeneous results for populations from the United States or Europe. A high BMI was weakly associated with the risk of cardia adenocarcinoma (OR, 1.5; 95% CI, 1.3-1.8; Pheterogeneity = 0.38).

Conclusions: Pooled results from observational studies support a positive association between high BMI and the risk for esophageal and possibly for cardia adenocarcinoma. (Cancer Epidemiol Biomarkers Prev 2006;15(5):872–8)
Statin Use and Risk of Lymphoid Neoplasms: Results from the European Case-Control Study EPILYMPH
Authors: Fortuny Joan , de Sanjosé Sílvia , Becker Nikolaus , Maynadié Marc , Cocco Pier Luigi , Staines Anthony , Foretova Lenka , Vornanen Martine , Brennan Paul , Nieters Alexandra , Alvaro Tomàs , Boffetta Paolo
Published: May 2006

Background: Statins, drugs used to treat dyslipidemia, may have anticancer properties. We have evaluated lymphoma risk associated with regular statin use in an international case-control study.

Methods: This case-control study included 2,362 cases of incident B- and T-cell lymphoma from Czech Republic, France, Germany, Ireland, Italy, and Spain and 2,206 hospital or population controls. Information on drug use, diagnosis at admission (for hospital controls), and putative risk factors for lymphoma was collected with personal interviews. Hospital controls admitted for diseases possibly entailing use of statins were excluded from the analysis.

Results: The odds ratio for regular statin use was 0.61 (95% confidence interval, 0.45-0.84); all major lymphoma subtypes showed similarly decreased risks. Decreased risks were observed in all centers. Duration of statin use was not associated with a greater reduction in the risk of lymphoma. Use of other lipid lowering drugs, such as fibrates, did not significantly modify the risk of lymphoma (odds ratio, 0.75; 95% confidence interval, 0.44-1.27).

Conclusion: Statin use was associated with an important reduction in lymphoma risk, adding to the growing evidence of anticancer properties of this group of drugs. These results are reassuring for the increasing number of patients taking statins on a regular basis. (Cancer Epidemiol Biomarkers Prev 2006;15(5):921–5)
Sequence Variants in Toll-Like Receptor 10 Are Associated with Nasopharyngeal Carcinoma Risk
Authors: Zhou Xin-Xi , Jia Wei-Hua , Shen Guo-Ping , Qin Hai-de , Yu Xing-Juan , Chen Li-Zhen , Feng Qi-Sheng , Shugart Yin Yao , Zeng Yi-Xin
Published: May 2006

Nasopharyngeal carcinoma (NPC) is a common malignancy in southern China and Southeast Asia. Genetic susceptibility is a major factor in determining the individual risk of NPC in these areas. To test the association between NPC and variants in Toll-like receptor 10 (TLR10), we conducted a hospital-based case-control study in a Cantonese-speaking population in Guangdong province. Seven single nucleotide polymorphisms in TLR10, selected with a tagging algorithm, were genotyped. When assessing each unique haplotype compared with the most common haplotype, “GAGTGAA,” with the expectation-maximization algorithm in Haplo.stats, the risk of developing NPC was significantly elevated among men who carried the haplotype “GCGTGGC” (P = 0.005). After adjusting for age, gender, and VCA-IgA antibody titers, this association was more significant (P = 0.0007). To further assess the overall differences of haplotype frequency profiles between cases and healthy controls, the global score test, considering all haplotypes and adjusting for age, gender, and VCA-IgA antibody titers, gave a haplo score of 27.52 with P = 0.002. The haplotype specific odds ratio was 2.66 (confidence interval, 1.34-3.82) for GCGTGGC. We concluded that in this Cantonese population–based study, haplotype GCGTGGC with frequency of 11.4% in TLR10 was found to be associated with NPC and this association was statistically significant after adjusting for age, gender, and VCA-IgA antibody titers. It is possible that this is not a causal haplotype for NPC; rather, it is in strong linkage disequilibrium with a causal single nucleotide polymorphism in close proximity. (Cancer Epidemiol Biomarkers Prev 2006;15(5):862–6)
Relationship between Established Breast Cancer Risk Factors and Risk of Seven Different Histologic Types of Invasive Breast Cancer
Authors: Li Christopher I. , Daling Janet R. , Malone Kathleen E. , Bernstein Leslie , Marchbanks Polly A. , Liff Jonathan M. , Strom Brian L. , Simon Michael S. , Press Michael F. , McDonald Jill A. , Ursin Giske , Burkman Ronald T. , Deapen Dennis , Spirtas Robert
Published: May 2006

Background: Important differences in the contributions of certain exposures to the risks of ductal versus lobular breast carcinomas have been observed, but few studies have evaluated the relationships between established breast cancer risk factors and other histologic types.

Methods: Information on family history of cancer and reproductive, hormonal, anthropometric, and lifestyle characteristics were collected in a multicenter population-based case-control study consisting of 3,463 ductal, 274 lobular, 261 ductal-lobular, 91 medullary, 77 tubular, 70 comedo, and 61 mucinous invasive breast carcinoma cases (ages 35-64 years, newly diagnosed 1994-1998) and 4,682 controls. Associations between each of these histologic types and various exposures were evaluated using polytomous regression.

Results: Heterogeneity in the risks of different histologic types of breast cancer was observed for three exposures: menopausal hormone use, body mass index (BMI), and alcohol consumption. Specifically, current use of unopposed estrogen was associated with a reduced risk of ductal carcinoma and increased risk of comedocarcinoma, and current use of estrogen and progestin was associated with elevated risks of ductal-lobular and tubular carcinomas. Among postmenopausal women, BMI was only inversely related to risk of ductal-lobular carcinoma, and alcohol use was only positively related to risk of lobular carcinoma.

Conclusions: Variations in the associations between known breast cancer risk factors and risk of different breast cancer histologies were observed. Although these findings require confirmation, and the analyses of some histologic groups were limited by small sample sizes, they provide some insight into the different etiologies of various histologic subtypes of breast cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(5):946–54)
Tobacco Smoking and Colorectal Hyperplastic and Adenomatous Polyps
Authors: Ji Bu-Tian , Weissfeld Joel L. , Chow Wong-Ho , Huang Wen-Yi , Schoen Robert E. , Hayes Richard B. ,   for the Prostate, Lung, Colorectal, and Ovarian Trial Team
Published: May 2006

Colorectal adenomas and possibly some hyperplastic polyps are precursors of colorectal cancer. Tobacco use is associated in epidemiologic studies with these polyps, although links between smoking and colorectal cancer are less consistent. To characterize the role of tobacco in early colorectal carcinogenesis, we compared tobacco use among 4,383 subjects with histologically verified benign (hyperplastic or adenomatous) polyps of the distal colon (descending colon, sigmoid, and rectum) with tobacco use among 33,667 subjects who were endoscopy negative for distal colon tumors, in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Trial, a randomized trial of flexible sigmoidoscopy. Risks, estimated by the odds ratio (OR), associated with current cigarette use were OR = 4.4 [95% confidence interval (95% CI), 3.7-5.2] for hyperplastic polyps only, OR = 1.8 (95% CI, 1.5-2.1) for adenomas only, and OR = 6.2 (95% CI, 4.7-8.3) for subjects with both hyperplastic and adenomatous polyps concurrently. Effects were weaker among ex smokers; the smoking-associated ORs remained consistently higher for hyperplastic polyps. This pattern was also seen in relation to cigarettes smoked per day, smoking duration, and pack-years. Tobacco-associated risks for multiple polyps were also stronger when hyperplastic disease was involved. In conclusion, tobacco use, particularly recent use, increases risk for both adenomatous and hyperplastic polyps, but the risks are substantially greater for hyperplastic lesions. (Cancer Epidemiol Biomarkers Prev 2006;15(5):897–901)
Common Genetic Variation at PTEN and Risk of Sporadic Breast and Prostate Cancer
Authors: Haiman Christopher A. , Stram Daniel O. , Cheng Iona , Giorgi Elena E. , Pooler Loreall , Penney Kathryn , Le Marchand Loïc , Henderson Brian E. , Freedman Matthew L.
Published: May 2006

PTEN frequently shows loss of heterozygosity in breast and prostate cancers, and mutations in this gene are responsible for Cowden disease, a rare Mendelian syndrome that includes breast cancer as part of its phenotype. Thus, PTEN serves as a candidate susceptibility gene for both breast and prostate cancer risk. Whether common inherited variation (either coding or noncoding) at the PTEN locus contribute to nonfamilial, sporadic breast and prostate cancer risk is not known. In this study, we employed a linkage disequilibrium–based approach to test for association between common genetic variation at the PTEN locus and breast and prostate cancer risk in African-American, Native Hawaiian, Japanese, Latina, and White men and women in the Multiethnic Cohort Study. We genotyped 17 common single nucleotide polymorphisms (SNP; ≥5% frequency in at least one ethnic group) spanning the PTEN gene to define the common alleles in these populations. These SNPs were in strong linkage disequilibrium, indicating that our survey captured most of the common sequence variation across this locus. Eight tagging SNPs were selected to predict the common PTEN haplotypes (≥0.05 frequency) in these populations (two additional tagging SNPs were required for African Americans). These SNPs were evaluated in a breast cancer case-control study (cases, n = 1,615; controls, n = 1,962) and prostate cancer case-control study (cases, n = 2,320; controls, n = 2,290) nested within the Multiethnic Cohort Study. Multiple testing was explicitly accounted for by applying a permutation-based framework. We found no strong association with any common haplotype in relation to breast or prostate cancer risk. In summary, our results show that common variants in PTEN do not substantially influence risk of these two common cancers. (Cancer Epidemiol Biomarkers Prev 2006;15(5):1021-1024)
NAD(P)H:Quinone Oxidoreductase 1 (NQO1) Pro187Ser Polymorphism and the Risk of Lung, Bladder, and Colorectal Cancers: a Meta-analysis
Authors: Chao Chun , Zhang Zuo-Feng , Berthiller Julien , Boffetta Paolo , Hashibe Mia
Published: May 2006

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme that catalyzes the two-electron reduction of quinoid compounds into hydroquinones, their less toxic form. A sequence variant at position 609 (C → T) in the NQO1 gene encodes an enzyme with reduced quinone reductase activity in vitro and thus was hypothesized to affect cancer susceptibility. We conducted meta-analyses focusing on three cancer sites (lung, bladder, and colorectum) to summarize the findings from the current literature and to explore sources of heterogeneity.

Results: There is no clear association between the NQO1 Pro187Ser polymorphism and lung cancer risk in the three ethnic groups examined: odds ratio (ORWhite) C/T + T/T versus C/C = 1.04 [95% confidence interval (95% CI), 0.96-1.13], ORAsian = 0.99 (95% CI, 0.72-1.34), and ORBlacks = 0.95 (95% CI, 0.66-1.36). However, a modestly increased risk was suggested for the variant homozygotes in whites (OR T/T versus C/C, 1.19; 95% CI, 0.94-1.50). Analysis excluding one outlier study suggested the variant allele may be associated with reduced lung cancer risk in Asians. Meta-analyses for bladder and colorectal cancer suggested a statistically significant association with the variant genotypes in whites. In stratified analyses, the NQO1 Pro187Ser variant genotypes were associated with slightly increased lung cancer risk in white ever smokers but not in white never smokers and were mainly associated with a reduced risk of lung adenocarcinoma but not squamous cell carcinoma in Asians.

Conclusions: Results from our meta-analyses suggest that the variant NQO1 Pro187Ser genotype may affect individual susceptibility to lung, bladder, and colorectal cancer. Such effects of the NQO1 polymorphism seem to be modified by ethnicity and smoking status. (Cancer Epidemiol Biomarkers Prev 2006;15(5):979–87) (Cancer Epidemiol Biomarkers Prev 2006;15(5):979-986)
Role of the Nijmegen Breakage Syndrome 1 Gene in Familial and Sporadic Prostate Cancer
Authors: Hebbring Scott J. , Fredriksson Henna , White Kirsten A. , Maier Christiane , Ewing Charles , McDonnell Shannon K. , Jacobsen Steven J. , Cerhan James , Schaid Daniel J. , Ikonen Tarja , Autio Ville , Tammela Teuvo L.J. , Herkommer Kathleen , Paiss Thomas , Vogel Walther , Gielzak Marta , Sauvageot Jurga , Schleutker Johanna , Cooney Kathleen A. , Isaacs William , Thibodeau Stephen N.
Published: May 2006

The Nijmegen breakage syndrome 1 (NBS1) gene, which participates in DNA double strand break repair, has been postulated to be a susceptibility factor for a number of cancers, including prostate cancer. Numerous mutations have been identified in NBS1, including the founder mutation 657del5. In this study, a number of analyses were done to determine whether mutations in NBS1 are associated with an increased risk for prostate cancer. The frequency of the 657del5 mutation in both familial prostate cancer cases (1,819 affected men among 909 families) and sporadic prostate cancer cases (1,218 affected men) collected from five centers participating in the International Consortium for Prostate Cancer Genetics were compared with that found in 697 normal controls. Seven individuals were identified to carry the mutation among the 3,037 cases screened: four in the familial group (three from one family and one from another) and three in the sporadic cases. The carrier frequency was 0.22% (2 of 909) for the probands and 0.25% (3 of 1,218) for the sporadic cases of prostate cancer. The 657del5 mutation was not detected in either the 293 unaffected members of the prostate cancer families or in the 697 control samples tested. The entire NBS1 gene was also sequenced in 20 of the youngest affected individuals from the Finnish group of familial cases to identify the presence of possible mutations in this high-risk group. One rare (D95N) and one common (E185Q) missense alteration was identified. More detailed analyses of the E185Q polymorphism, along with a third rare variant (R215W), failed to show an association with prostate cancer. Because the 657del5 mutation was absent from the control population, we are unable to determine if this alteration predisposes to prostate cancer. However, our data does suggest that mutations within NBS1, and in particular, 657del5, do not significantly contribute to the overall prostate cancer burden within our patient samples. (Cancer Epidemiol Biomarkers Prev 2006;15(5):935–8)
Alcohol Dehydrogenase 2 His47Arg Polymorphism Influences Drinking Habit Independently of Aldehyde Dehydrogenase 2 Glu487Lys Polymorphism: Analysis of 2,299 Japanese Subjects
Authors: Matsuo Keitaro , Wakai Kenji , Hirose Kaoru , Ito Hidemi , Saito Toshiko , Tajima Kazuo
Published: May 2006

Although the functional effect of alcohol dehydrogenase 2 (ADH2) His47Arg polymorphism has been elucidated, its effect on habitual drinking remains unknown. Here, we conducted a cross-sectional study in 2,299 nonalcoholic Japanese subjects (989 men and 1,310 women). Drinking status, ethanol consumption, and physical reaction to one glass of beer were examined with regard to ADH2 and aldehyde dehydrogenase 2 (ALDH2) polymorphism. Strength of associations were assessed by age-, sex-, smoking status-, and genotype-adjusted odds ratios and their 95% confidence intervals. ADH2 His/Arg and Arg/Arg genotypes showed higher risk for habitual drinking. Among men, ALDH2 genotype- and confounder-adjusted odds ratios (95% confidence intervals) were 1.30 (0.89-1.89) and 3.16 (1.03-9.70), and this trend was significant (P = 0.024). A similar trend was observed among women. The combination genotypes of two polymorphisms revealed the clear effect of the ADH2 Arg allele among those with ALDH2 Glu/Lys in both sexes (Ptrend = 0.007 for men and 0.024 for women). Physical reactions, such as flushing and palpitation, were significantly less common in those with Arg/Arg compared with other ADH2 genotypes, and this was marked when combined with ALDH2 Glu/Lys. Heavy drinker status was also strongly associated with ADH2 Arg alleles. In conclusion, this study showed the strong effect of ADH2 His47Arg polymorphism on habitual drinking regardless of ALDH2 genotype. (Cancer Epidemiol Biomarkers Prev 2006;15(5):1009–13)
Smokers at Higher Risk for Undetected Antibody for Oncogenic Human Papillomavirus Type 16 Infection
Authors: Wiley Dorothy J. , Wiesmeier Edward , Masongsong Emmanuel , Gylys Karen H. , Koutsky Laura A. , Ferris Daron G. , Barr Eliav , Yu Rao Jian ,   The Proof of Principle Study Investigative Group
Published: May 2006

Objective: To determine the association between tobacco smoking and serologic evidence of human papillomavirus type 16 (HPV16)–specific antibodies among HPV16 DNA–positive women.

Design, Setting, and Participants: Baseline health history, physical examination, and laboratory data for 205 HPV16 DNA–positive women with no prior cytologic evidence of squamous intraepithelial lesions who were enrolled subsequently in a randomized clinical trial.

Main Outcome Measure: HPV16-L1 antibody (anti-HPV16 antibody) detected from serum using RIA or ELISA.

Results: Eighty-seven percent (179 of 205) of women tested positive for HPV16 DNA using cervicovaginal swabs or lavage specimens, and 26 women showed similar results using swab specimens of external genitalia alone. HPV16-infected women who reported increasingly greater levels of daily cigarette smoking were less likely to test positive for anti-HPV16 antibodies than nonsmoking women (P = 0.02). Smokers were twice as likely as nonsmokers to test negative for anti-HPV16 antibodies, even after controlling for the effects of other covariates in the analyses (adjusted odds ratio, 0.5; 95% confidence limits, 0.2-0.9). Although Papanicolaou test findings and smoking characteristics were poorly correlated (r2 = 0.01), women who showed atypical cells of unknown significance or squamous intraepithelial lesion were twice as likely to test anti-HPV16 antibody positive as women who showed normal Papanicolaou tests (adjusted odds ratio, 2.0; 95% confidence limits, 1.1-3.7).

Conclusion: These data suggest that smoking may influence the long-term risk for cancer by perturbing early immune responses to the virus and may increase the likelihood of persistent infection. Patient education messages should alert women to this additional risk of smoking. A clinical trial of smoking cessation should be explored as a therapeutic intervention for primary HPV16 infection. (Cancer Epidemiol Biomarkers Prev 2006;15(5):915–20)
The Association of Plasma DHEA and DHEA Sulfate with Breast Cancer Risk in Predominantly Premenopausal Women
Authors: Tworoger Shelley S. , Missmer Stacey A. , Eliassen A. Heather , Spiegelman Donna , Folkerd Elizabeth , Dowsett Mitch , Barbieri Robert L. , Hankinson Susan E.
Published: May 2006

Concentrations of adrenal androgens are positively associated with postmenopausal breast cancer risk; however, results in premenopausal women are conflicting. Therefore, we conducted a prospective nested case-control study within the Nurses' Health Study II cohort to examine the relationship of DHEA and DHEA sulfate (DHEAS) with breast cancer risk in predominantly premenopausal women. Blood samples were collected from 1996 to 1999. The analysis included 317 cases of breast cancer diagnosed after blood collection and before June 1, 2003; for each case, two controls were matched on age, fasting status, time of day and month of blood collection, race/ethnicity, and timing of blood draw within the menstrual cycle. No associations were observed between DHEA or DHEAS levels and breast cancer risk overall [in situ and invasive; DHEA relative risk (RR), top versus bottom quartile, 1.2; 95% confidence interval (95% CI), 0.8-1.8, Ptrend = 0.53; DHEAS RR, 1.3; 95% CI, 0.9-2.0; Ptrend = 0.07]. However, both DHEA and DHEAS were positively associated with estrogen receptor–positive/progesterone receptor–positive breast cancer (DHEA RR, 1.6; 95% CI, 0.9-2.8, Ptrend = 0.09; DHEAS RR, 1.9; 95% CI, 1.1-3.3, Ptrend = 0.02). We observed a significant interaction by age, with an RR for DHEAS of 0.8 (95% CI, 0.4-1.5, Ptrend = 0.62) for women <45 years old and 2.0 (95% CI, 1.2-3.5, Ptrend = 0.003) for women ≥45 years old; results were similar for DHEA. Our results suggest that adrenal androgens are positively associated with breast cancer among predominately premenopausal women, especially for estrogen receptor–positive/progesterone receptor–positive tumors and among women over age 45 years. (Cancer Epidemiol Biomarkers Prev 2006;15(5):967–71)
Selenomethionine Treatment Does Not Alter Gene Expression in Normal Squamous Esophageal Mucosa in a High-Risk Chinese Population
Authors: Joshi Nina , Johnson Laura Lee , Wei Wen-Qiang , Abnet Christian C. , Dong Zhi-Wei , Taylor Philip R. , Limburg Paul J. , Dawsey Sanford M. , Hawk Ernest T. , Qiao You-Lin , Kirsch Ilan R.
Published: May 2006

Selenium is a promising cancer chemoprevention agent. A recent randomized controlled chemoprevention trial found that selenomethionine (SeMet) supplementation for 10 months favorably effected a change in esophageal dysplasia grade among participants who started the trial with mild dysplasia. To further explore the role of SeMet in this trial, we compared gene expression profiles by treatment group using Affymetrix HU 133A chips in before/after supplementation paired normal esophageal biopsies from a subset of 29 trial participants, 16 who received SeMet, and 13 who received placebo. Using P < 0.001 as a cutoff, 11 differentially expressed genes were found in the SeMet supplementation group but these genes did not include either known selenoprotein genes or genes previously shown to be modulated by selenium treatment. Because the number of differentially expressed genes (n = 11) was less than expected by chance (n = 18), we concluded that SeMet supplementation had no measurable effect on gene expression in the normal squamous esophagus of these subjects with dysplasia. (Cancer Epidemiol Biomarkers Prev 2006;15(5):1046-7)
Understanding Population and Individual Risk Assessment: The Case of Polychlorinated Biphenyls
Authors: Shields Peter G.
Published: May 2006

Decisions about how to improve or protect the public health can be, and sometimes necessarily are, made on imprecise science. The regulation of potential human carcinogens in the environment entails a population-risk assessment process intended to reduce risks to less than one additional cancer in 100,000 or 1,000,000 persons. These risk assessment processes, however, may be miscommunicated or misinterpreted in the context of individual cancer risks by scientists, regulators, the lay media, and the public. This commentary will review methods for establishing a causal relationship between carcinogen exposures and cancer risk. It will use the case of polychlorinated biphenyls (PCB) as an example of how to place scientific data into the context of human exposure and cancer risk. PCBs are widespread environmental contaminants and most people have detectable levels of PCBs in their bodies. The primary source for exposure in the general population is through the diet. PCBs are carcinogens in experimental animal models, but how this information can be extrapolated to human risk remains uncertain. PCB experimental studies provide data that are used to regulate and control human exposure, although the epidemiologic evidence fails to establish PCBs as human carcinogens. Thus, what is used for population-risk assessment may not be appropriate for individual-risk assessment or concluding that a causal relationship exists between PCB exposure and cancer risk. The hazards from a carcinogen designated by regulatory and review agencies as a “probable” human carcinogen is often misunderstood out of context about the magnitude of the risk and in what settings. How scientists communicate their results in scientific articles can strongly influence how others interpret their data. Misunderstandings from both the use of regulatory and review-agency opinions and the conclusions espoused by scientists occur in the media, among private physicians counseling their patients about cancer risk, and in the legal settings where plaintiffs seek compensation for exposure and alleged harm (or future harm). This can lead to false conclusions about what caused a cancer in a specific patient, undue anxiety about future cancer risk, inappropriate cancer screening, and attendant increased morbidity due to increased uses of the medical system and complication rates from medical procedures. The communication of research findings by scientists must be presented with caution, resisting the temptation to extrapolate, inappropriately, research data to the general population. (Cancer Epidemiol Biomarkers Prev 2006;15(5):830–9)
Outcomes of Children Bridged to Heart Transplantation With Ventricular Assist Devices
Authors: Blume Elizabeth D. , Naftel David C. , Bastardi Heather J. , Duncan Brian W. , Kirklin James K. , Webber Steven A.
Published: May 2006

Background—

Current ventricular assist devices (VADs) in the United States are designed primarily for adult use. Data on VADs as a bridge to transplantation in children are limited.

Methods and Results—

A multi-institutional, prospectively maintained database of outcomes in children after listing for heart transplantation (n=2375) was used to analyze outcomes of VAD patients (n=99, 4%) listed between January 1993 and December 2003. Median age at VAD implantation was 13.3 years (range, 2 days to 17.9 years); diagnoses were cardiomyopathy (78%) and congenital heart disease (22%). Mean duration of support was 57 days (range, 1 to 465 days). Seventy-three percent were supported with a long-term device, with 39% requiring biventricular support. Seventy-seven patients (77%) survived to transplantation, 5 patients were successfully weaned from support and recovered, and 17 patients (17%) died on support. In the recent era (2000 to 2003), successful bridge to transplantation with VAD was achieved in 86% of patients. Peak hazard for death while waiting was the first 2 weeks after VAD placement. Risk factors for death while awaiting a transplant included earlier era of implantation (
P
=0.05), female gender (
P
=0.02), and congenital disease diagnosis (
P
=0.05). There was no difference in 5-year survival after transplantation for patients on VAD at time of transplantation as compared with those not requiring VAD.

Conclusions—

VAD support in children successfully bridged 77% of patients to transplantation, with posttransplantation outcomes comparable to those not requiring VAD. These encouraging results emphasize the need to further understand patient selection and to delineate the impact of VAD technology for children.
Biogeography of Neurergus strauchii barani Öz, 1994 and N. s. strauchii (Steindachner, 1887) (Amphibia: Salamandridae) assessed using morphological and molecular data
Authors: Woeltjes Tonnie , Bogaerts Sergé , Carranza Salvador , Pasmans Frank
Published: May 2006

Five new locations of N. strauchii are reported from Turkey, closing the gap between the two subspecies N. s. barani and N. s. strauchii. A molecular analysis based on 829 base pairs from two mitochondrial ribosomal genes (12S and 16S rRNA), together with geographical data from the area concerned, indicate all new populations found are very closely related to the mitochondrial sequences from specimens of N. s. strauchii from its type locality and suggest the river Euphrates might have acted as a natural barrier separating the only populations of N. s. barani known to date from all other populations of N. s. strauchii. A morphological analysis of all N. strauchii populations sampled for this study indicates that belly patterns are not a good diagnostic character to differentiate between N. s. barani and N. s. strauchii, suggesting the only reliable morphological taxonomic character that allows their identification is the different number of yellow spots in adult specimens, which is significantly higher in N. s. strauchii. The analyses also indicate that the number of spots is similar between sub-adult and adult N. s. barani but significantly different between sub-adult and adult specimens of N. s. strauchii, suggesting there is also a difference between both subspecies in increase in the number of spots during maturation.Listed by IUCN as vulnerable and protected by the Bern Convention (1979), our findings indicate N. s. strauchii is more widely distributed than previously thought, while N. s. barani would be restricted to just a few localities. Disturbance of its prime habitat, mountain brooks, and uncontrolled illegal collection, especially of N. s. barani, are still the main threats to the Anatolia newt throughout its known distribution range.
Home range area may vary considerably in relation to habitat contamination in two African terrapins from pristine and oil polluted habitats
Authors: Bello  , Ude  , Luiselli  , Akani  , Angelici
Published: May 2006

Home range and nesting habitat were studied in two sympatric pelomedusid terrapins (Pelusios niger and Pelusios castaneus) from two study areas in the Niger Delta (Nigeria, West Africa), one with pristine habitat conditions and one which was polluted by a oil spill event some years before. Seventy-seven individuals (38 P. niger and 39 P. castaneus) were radiotracked, each for more than 60 days, and their home range was calculated by the minimum convex polygon method, with 95% of the point locations per individual. The mean home range size of females was significantly larger in the polluted area than in the pristine area in both P. niger and P. castaneus, and the mean home range size of female P. niger was significantly larger than that of female P. castaneus in the polluted area, but not in the pristine area. The mean home range size of males was significantly larger in the polluted area than in the pristine area in P. niger but not in P. castaneus, and the mean home range size of male P. niger was significantly larger than that of male P. castaneus in the polluted area but not in the pristine area. Radiotracked females of both species showed a clear preference for nesting sites situated along ponds and not along the banks of the river, on sandy soil, often with abundant vegetation around. Some females of both species deposited their eggs at greater distances from water bodies in the polluted area than in the pristine area. The comparative evidence of these patterns indicates consistent responses of the two species to the altered habitat, which further supports the general hypothesis that habitat pollution has seriously affected the ecological strategies of these terrapin species.
Improving data analysis in herpetology: using Akaike's Information Criterion (AIC) to assess the strength of biological hypotheses
Authors: Mazerolle Marc
Published: May 2006

In ecology, researchers frequently use observational studies to explain a given pattern, such as the number of individuals in a habitat patch, with a large number of explanatory (i.e., independent) variables. To elucidate such relationships, ecologists have long relied on hypothesis testing to include or exclude variables in regression models, although the conclusions often depend on the approach used (e.g., forward, backward, stepwise selection). Though better tools have surfaced in the mid 1970's, they are still underutilized in certain fields, particularly in herpetology. This is the case of the Akaike information criterion (AIC) which is remarkably superior in model selection (i.e., variable selection) than hypothesis-based approaches. It is simple to compute and easy to understand, but more importantly, for a given data set, it provides a measure of the strength of evidence for each model that represents a plausible biological hypothesis relative to the entire set of models considered. Using this approach, one can then compute a weighted average of the estimate and standard error for any given variable of interest across all the models considered. This procedure, termed model-averaging or multimodel inference, yields precise and robust estimates. In this paper, I illustrate the use of the AIC in model selection and inference, as well as the interpretation of results analysed in this framework with two real herpetological data sets. The AIC and measures derived from it is should be routinely adopted by herpetologists.