bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin versus Lipid Emulsion in a Rabbit Model of Severe Propranolol Toxicity: A Pilot Study
Authors: Harvey Martyn , Cave Grant , Lahner Daniel , Desmet Jan , Prince Gaynor , Hopgood Gary
Published: March 2011

Background and objective. Beta-blocker overdose may result in intractable cardiovascular collapse despite conventional antidotal treatments. High dose insulin/glucose (ING), and more recently intravenous lipid emulsion (ILE), have been proposed as potentially beneficial therapies in beta blocker intoxication. We compare efficacy of the novel antidotes ING, with ILE, in a rabbit model of combined enteric/intravenous propranolol toxicity.Methods. Sedated, mechanically ventilated and invasively monitored New Zealand White rabbits underwent mini-laparotomy and enterostomy formation with 40 mg/kg propranolol instilled into the proximal small bowel. At 30 minutes propranolol infusion was commenced at 4 mg/kg/hr and continued to a target mean arterial pressure (MAP) of 50% baseline MAP. Animals were resuscitated with insulin at 3 U/kg plus 0.5 g/kg glucose (ING group), or 10 mL/kg 20% Intralipid (ILE group).Results. Rate pressure product (RPP; RPP = heart rate × mean arterial pressure) was greatest in the ING group at 60 minutes (P<.05). A trend toward greater heart rate was observed in the ING group (P=.06). No difference was observed in survival between groups (4/5 ING versus 2/5 ILE;P=.524).Conclusions. High dose insulin resulted in greater rate pressure product compared with lipid emulsion in this rabbit model of severe enteric/intravenous propranolol toxicity.
Flourensia cernua: Hexane Extracts a Very Active Mycobactericidal Fraction from an Inactive Leaf Decoction against Pansensitive and Panresistant Mycobacterium tuberculosis
Authors: Molina-Salinas Gloria María , Peña-Rodríguez Luis Manuel , Mata-Cárdenas Benito David , Escalante-Erosa Fabiola , González-Hernández Silvia , Torres de la Cruz Víctor Manuel , Martínez-Rodríguez Herminia Guadalupe , Said-Fernández Salvador
Published: March 2011

The efficacy of decoction in extracting mycobactericidal compounds from Flourensia cernua (Hojasé) leaves and fractionation with solvents having ascending polarity was compared with that of (i) ethanol extraction by still maceration, extraction with a Soxhlet device, shake‐assisted maceration, or ultrasound‐assisted maceration, followed by fractionation with n‐hexane, ethyl acetate, and n‐butanol; (ii) sequential extraction with n‐hexane, ethyl acetate, and n‐butanol, by still maceration, using a Soxhlet device, shake‐assisted maceration, or ultrasound‐assisted maceration. The in vitro mycobactericidal activity of each preparation was measured against drug‐sensitive (SMtb) and drug‐resistant (RMtb) Mycobacterium tuberculosis strains. The results of which were expressed as absolute mycobactericidal activity (AMA). These data were normalized to the ΣAMA of the decoction fraction set. Although decoction was inactive, the anti‐RMtb normalized ΣAMA (NAMA) of its fractions was comparable with the anti‐RMtb NAMA of the still maceration extracts and significantly higher than the anti‐SMtb and anti‐RMtb NAMAs of every other ethanol extract and serial extract and fraction. Hexane extracted, from decoction, material having 55.17% and 92.62% of antituberculosis activity against SMtb and RMtb, respectively. Although the mycobactericidal activity of decoction is undetectable; its efficacy in extracting F. cernua active metabolites against M. tuberculosis is substantially greater than almost all pharmacognostic methods.
A q-Weibull Counting Process through a Fractional Differential Operator
Authors: Muralidharan Kunnummal , Nair Seema S.
Published: March 2011

We use the q-Weibull distribution and define a new counting process using the fractional order. As a consequence, we introduce a q-process with q-Weibull interarrival times. Some interesting special cases are also discussed which leads to a Mittag-Leffler form.
Hamilton‐Poisson Realizations for the Lü System
Authors: Pop Camelia , Petrişor Camelia , Bălă Dumitru
Published: March 2011

The Hamilton‐Poisson geometry has proved to be an interesting approach for a lot of dynamics arising from different areas like biology (Gümral and Nutku, 1993), economics (Dănăiasă et al., 2008), or engineering (Ginoux and Rossetto, 2006). The Lü system was first proposed by Lü and Chen (2002) as a model of a nonlinear electrical circuit, and it was studied from various points of view. We intend to study it
from mechanical geometry point of view and to point out some of its geometrical and dynamical properties.
Fabrication of Biodegradable Polyester Nanocomposites by Electrospinning for Tissue Engineering
Authors: Xing Zhi-Cai , Han Seung-Jin , Shin Yong-Suk , Kang Inn-Kyu
Published: March 2011

Recently, nanocomposites have emerged as an efficient strategy to upgrade the structural and functional properties of synthetic polymers. Polyesters have attracted wide attention because of their biodegradability and biocompatibility. A logic consequence has been the introduction of natural extracellular matrix (ECM) molecules, organic or inorganic nanostructures to biodegradable polymers to produce nanocomposites with enhanced properties. Consequently, the improvement of the interfacial adhesion between biodegradable polymers and natural ECM molecules or nanostructures has become the key technique in the fabrication of nanocomposites. Electrospinning has been employed extensively in the design and development of tissue engineering scaffolds to generate nanofibrous substrates of synthetic biodegradable polymers and to simulate the cellular microenvironment. In this paper, several types of biodegradable polyester nanocomposites were prepared by electrospinning, with the aim of being used as tissue engineering scaffolds. The combination of biodegradable nanofibrous polymers and natural ECM molecules or nanostructures opens new paradigms for tissue engineering applications.
BD-ProExC as Adjunct Molecular Marker for Improved Detection of CIN2+ after HPV Primary Screening
Authors: Depuydt Christophe E. , Makar Amin P. , Ruymbeke Maya J. , Benoy Ina H. , Vereecken Annie J. , Bogers Johannes J.
Published: March 2011

Background and Methods: We investigated the efficacy of 8 cervical cancer screening strategies relative to cytology with emphasis on immunocytochemical detection of high-risk human papillomavirus (hrHPV)-induced cell transformation (BD-ProExC) as a tool of triage following primary cytology or hrHPV testing. 3,126 women were tested with BD-SurePath liquid-based cytology, hrHPV PCR genotyping and BD-ProExC immunostaining, and colposcopy verification to calculate sensitivity and positive predictive value (PPV) in detecting cervical intraepithelial neoplasia (CIN2+).

Results: Compared to cytology screening, double testing with cytology and hrHPV resulted in the same sensitivity with a significant increase in the PPV (relative PPV: 1.83). However, twice as many tests were needed. Cytology with atypical squamous cells of undetermined significance (ASC-US) triage and hrHPV testing showed comparative results to double testing requiring only a small increase in number of tests. Screening for hrHPV subtypes 16/18, and ASC-US triage with hrHPV16/18 resulted in significant reductions in sensitivity (ratio: 0.74 and 0.96, respectively). Primary hrHPV/BD-ProExC screening was significantly more sensitive (ratio: 1.63/1.33), but had a significantly lower PPV (ratio: 0.64/0.88). ASC-US triage by BD-ProExC increased the PPV (ratio: 1.90) but decreased the sensitivity (ratio: 0.96). Primary hrHPV screening followed by BD-ProExC triage, led to significant increases in sensitivity (ratio: 1.30) and PPV (ratio: 2.89), and resulted in 55% fewer referrals for colposcopy.

Conclusions: From the investigated screening strategies, primary hrHPV DNA-based screening followed by BD-ProExC triage was determined to be the best screening strategy.

Impact: Immunocytological triage could be used to perfect hrHPV primary screening. Cancer Epidemiol Biomarkers Prev; 20(4); 628–37. ©2011 AACR.
Ultraviolet Exposure and Mortality among Women in Sweden
Authors: Yang Ling , Lof Marie , Veierød Marit Bragelien , Sandin Sven , Adami Hans-Olov , Weiderpass Elisabete
Published: March 2011

Background: Ecological studies have reported possible effects of sunlight on the risk of several diseases. Little evidence is available on the association between mortality and solar and artificial UV exposure by individual level from prospective studies.

Methods: The Swedish Women's Lifestyle and Health cohort study included women aged 30 to 49 years in 1991–1992. Participants completed a questionnaire and were followed-up through linkages to national registries until the end of 2006. Cox models were used to estimate adjusted HRs and 95% CIs for all-cause mortality and for cancer and cardiovascular disease (CVD) mortality.

Results: During 15 years of follow-up, among the 38,472 women included in the present study, 754 deaths occurred: 457 due to cancer and 100 due to CVD. When combining the information on sun exposure from age 10 to 39 years, women who got sunburned twice or more per year during adolescence had a reduced all-cause mortality, compared with women who had been sunburned once or less. A reduced risk for all-cause and CVD mortality was observed in women who went on sunbathing vacations more than once a year over three decades. Solarium use once or more per month for at least one decade increased the risk of all-cause mortality, when compared with women who never used a solarium.

Conclusions: Solar UV exposure was associated with reduced overall and CVD mortality, whereas artificial UV exposure was associated with increased overall and cancer mortality among Swedish women.

Impact: Moderate sun exposure may protect against cause-specific mortality. Cancer Epidemiol Biomarkers Prev; 20(4); 683–90. ©2011 AACR.
A Sex-Specific Association between a 15q25 Variant and Upper Aerodigestive Tract Cancers
Authors: Chen Dan , Truong Therese , Gaborieau Valerie , Byrnes Graham , Chabrier Amelie , Chuang Shu-chun , Olshan Andrew F. , Weissler Mark C. , Luo Jingchun , Romkes Marjorie , Buch Shama , Nukui Tomoko , Franceschi Silvia , Herrero Rolando , Talamini Renato , Kelsey Karl T. , Christensen Brock , McClean Michael D. , Lacko Martin , Manni Johannes J. , Peters Wilbert H. M. , Lubiński Jan , Trubicka Joanna , Lener Marcin , Muscat Joshua E. , Lazarus Philip , Wei Qingyi , Sturgis Erich M. , Zhang Zuo-Feng , Chang Shen-Chih , Wang Renyi , Schwartz Stephen M. , Chen Chu , Benhamou Simone , Lagiou Pagona , Holcátová Ivana , Richiardi Lorenzo , Kjaerheim Kristina , Agudo Antonio , Castellsagué Xavier , Macfarlane Tatiana V. , Barzan Luigi , Canova Cristina , Thakker Nalin S. , Conway David I. , Znaor Ariana , Healy Claire M. , Ahrens Wolfgang , Zaridze David , Szeszenia-Dabrowska Neonila , Lissowska Jolanta , Fabianova Eleonora , Bucur Alexandru , Bencko Vladimir , Foretova Lenka , Janout Vladimir , Curado Maria Paula , Koifman Sergio , Menezes Ana , Wünsch-Filho Victor , Eluf-Neto José , Fernandez Leticia , Boccia Stefania , Hashibe Mia , Hayes Richard B. , Boffetta Paolo , Brennan Paul , McKay James D.
Published: March 2011

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35).

Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case–control studies.

Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08–1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95–1.09, P = 0.66; P-heterogeneity (Phet) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12–1.34, P = 7 × 10−6) but not males (OR = 1.02, 95% CI = 0.97–1.08, P = 0.35; Phet = 6 × 10−4). There was little evidence for a sex

difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (Phet = 0.86).

Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers.

Impact: Further research is warranted to elucidate the mechanisms underlying these observations. Cancer Epidemiol Biomarkers Prev; 20(4); 658–64. ©2011 AACR.
Increased Plasma Soluble uPAR Level Is a Risk Marker of Respiratory Cancer in Initially Cancer-Free Individuals
Authors: Langkilde Anne , Hansen Tine W. , Ladelund Steen , Linneberg Allan , Andersen Ove , Haugaard Steen B. , Jeppesen Jørgen , Eugen-Olsen Jesper
Published: March 2011

Background: Soluble urokinase plasminogen activator receptor (suPAR) is a stable plasma biomarker associated with inflammation and disease. This study tested the association between suPAR levels and incident respiratory, gastrointestinal, or other types of cancer in initially cancer-free individuals from a general population-based prospective study.

Methods: Baseline plasma samples, baseline characteristics, and follow-up data were available from 2,656 individuals from the population-based Danish MONICA10 (MONItoring trends and determinants of CArdiovascular disease) study, followed for a median of 12.6 years. Cancer was diagnosed according to international classification of diseases (ICD) 8 and ICD-10 codes and suPAR levels were measured using a commercially available ELISA. The association of suPAR levels with incident cancer during follow-up was analyzed using Cox regression, adjusted for established risk factors and the inflammatory markers C-reactive protein (CRP) and leukocyte numbers.

Results: suPAR levels ranged from 0.6 to 22 ng/mL and median suPAR level was 4.01 ng/mL. An increase of 1 ng/mL in baseline suPAR was associated with adjusted HR of 1.61 (95% CI: 1.23–2.11, P < 0.001), 0.92 (95% CI: 0.69–1.24, P = 0.59), and 1.33 (95% CI: 1.13–1.58, P < 0.001) of being diagnosed with respiratory, gastrointestinal, and other cancer types, respectively.

Conclusion: Elevated suPAR levels were associated with increased risk of incident respiratory cancer and other types of cancer, but not gastrointestinal cancers, independently of established risk factors, CRP, and leukocyte numbers.

Impact: These findings suggest that inflammation is involved in cancer development. Risk algorithms based on established risk factors and risk-associated biomarkers should be developed and evaluated in large, general population-based studies. We suggest suPAR as a candidate for evaluation in cancer risk algorithms. Cancer Epidemiol Biomarkers Prev; 20(4); 609–18. ©2011 AACR.
Expression of SLCO Transport Genes in Castration-Resistant Prostate Cancer and Impact of Genetic Variation in SLCO1B3 and SLCO2B1 on Prostate Cancer Outcomes
Authors: Wright Jonathan L. , Kwon Erika M. , Ostrander Elaine A. , Montgomery R. Bruce , Lin Daniel W. , Vessella Robert , Stanford Janet L. , Mostaghel Elahe A.
Published: March 2011

Background: Metastases from men with castration-resistant prostate cancer (CRPC) harbor increased tumoral androgens versus untreated prostate cancers. This may reflect steroid uptake by OATP (organic anion transporting polypeptide)/SLCO transporters. We evaluated SLCO gene expression in CRPC metastases and determined whether prostate cancer outcomes are associated with single nucleotide polymorphisms (SNP) in SLCO2B1 and SLCO1B3, transporters previously shown to mediate androgen uptake.

Methods: Transcripts encoding eleven SLCO genes were analyzed in untreated prostate cancer and in metastatic CRPC tumors obtained by rapid autopsy. SNPs in SLCO2B1 and SLCO1B3 were genotyped in a population-based cohort of 1,309 Caucasian prostate cancer patients. Median survival follow-up was 7.0 years (0.77–16.4). The risk of prostate cancer recurrence/progression and prostate cancer–specific mortality (PCSM) was estimated with Cox proportional hazards analysis.

Results: Six SLCO genes were highly expressed in CRPC metastases versus untreated prostate cancer, including SLCO1B3 (3.6-fold; P = 0.0517) and SLCO2B1 (5.5-fold; P = 0.0034). Carriers of the variant alleles SLCO2B1 SNP rs12422149 (HR: 1.99; 95% CI: 1.11–3.55) or SLCO1B3 SNP rs4149117 (HR: 1.76; 95% CI: 1.00–3.08) had an increased risk of PCSM.

Conclusions: CRPC metastases show increased expression of SLCO genes versus primary prostate cancer. Genetic variants of SLCO1B3 and SLCO2B1 are associated with PCSM. Expression and genetic variation of SLCO genes which alter androgen uptake may be important in prostate cancer outcomes.

Impact: OATP/SLCO genes may be potential biomarkers for assessing risk of PCSM. Expression and genetic variation in these genes may allow stratification of patients to more aggressive hormonal therapy or earlier incorporation of nonhormonal-based treatment strategies. Cancer Epidemiol Biomarkers Prev; 20(4); 619–27. ©2011 AACR.
A Prospective Assessment of Racial/Ethnic Differences in Future Mammography Behavior among Women Who had Early Mammography
Authors: Kapp Julie M. , Walker Rod , Haneuse Sebastien , Yankaskas Bonnie C.
Published: March 2011

Background: Twenty-nine percent of women, aged 30 to 39, report having had a mammogram, though sensitivity and specificity are low. We investigate racial/ethnic differences in future mammography behavior among women who had a baseline screening mammogram prior to age 40.

Methods: Using 1994–2008 data from the Breast Cancer Surveillance Consortium (BCSC), we identified 29,390 women aged 35 to 39 with a baseline screening mammogram. We followed this cohort for 2 outcomes: (i) future BCSC mammography between ages 40 and 45; and (2) among those, delay in screening mammography until ages 43 to 45 compared with ages 40 to 42. Using adjusted log-linear models, we estimated the relative risk (RR) of these outcomes by race/ethnicity, while also considering the impact of false-positive/true-negative (FP/TN) baseline mammography results on these outcomes.

Results: Relative to non-Hispanic white women, Hispanic women had an increased risk of no future BCSC mammography (RR: 1.21, 95% CI: 1.13–1.30); Asian women had a decreased risk (RR: 0.67, 95% CI: 0.61–0.74). Women with a FP result, compared with a TN result, had a decreased risk of no future BCSC mammography (RR: 0.89, 95% CI: 0.85–0.95). Among those with future BCSC screening mammography, African American women were more likely to delay the timing (RR: 1.26, 95% CI: 1.09–1.45). The interaction between race/ethnicity and FP/TN baseline results was not significant.

Conclusions: Race/ethnicity is differentially associated with future BCSC mammography and the timing of screening mammography after age 40.

Impact: These findings introduce the need for research that examines disparities in lifetime mammography use patterns from the initiation of mammography screening. Cancer Epidemiol Biomarkers Prev; 20(4); 600–8. ©2011 AACR.
Early Natural History of Incident, Type-Specific Human Papillomavirus Infections in Newly Sexually Active Young Women
Authors: Winer Rachel L. , Hughes James P. , Feng Qinghua , Xi Long Fu , Cherne Stephen , O'Reilly Sandra , Kiviat Nancy B. , Koutsky Laura A.
Published: March 2011

Background: Characterizing short-term detection patterns of young women's incident α-genus human papillomavirus (HPV) infections may further our understanding of HPV transmission.

Methods: Between 2000 and 2007, we followed 18- to 22-year-old female university students with triannual HPV DNA and Papanicolaou testing. Using Kaplan–Meier methods, we estimated duration of detectable, type-specific incident infections; time to redetection (among infections that became undetectable); and time to cervical lesion development after incident infection. We evaluated risk factors for short-term persistent versus transient infection with logistic regression.

Results: Three hundred three incident, type-specific infections were detected in 85 sexually active women. Median time to first negative test after incident infection was 9.4 (95% CI: 7.8–11.2) months; 90.6% of infections became undetectable within 2 years. About 19.4% of infections that became undetectable were redetected within 1 year. Cervical lesions were common and 60% were positive for multiple HPV types in concurrent cervical swabs. Incident HPV detection in the cervix only (vs. the vulva/vagina only or both sites) was associated with short-term transience.

Conclusions: Although most incident infections became undetectable within 2 years, redetection was common. Cervical lesions were a common early manifestation of HPV infection.

Impact: It remains unclear whether potentially modifiable risk factors can be identified to reduce infection duration (and transmission likelihood). Cancer Epidemiol Biomarkers Prev; 20(4); 699–707. ©2011 AACR.
Increased Risk of Lung Cancer in Men with Tuberculosis in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study
Authors: Shiels Meredith S. , Albanes Demetrius , Virtamo Jarmo , Engels Eric A.
Published: March 2011

Background: Lung cancer and tuberculosis cause significant morbidity and mortality worldwide. Tuberculosis may increase lung cancer risk through substantial and prolonged pulmonary inflammation. However, prospective data on tuberculosis and lung cancer risk are limited.

Methods: Our study included 29,133 Finnish male smokers followed prospectively in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1985–2005). Lung cancers were identified through linkage with the Finnish Cancer Registry, and hospital-treated tuberculosis cases were ascertained from the National Hospital Discharge Register. We assessed the association between tuberculosis and lung cancer risk with proportional hazards regression models, adjusting for age and cigarette smoking.

Results: Forty-four lung cancer cases occurred among 273 men with tuberculosis (incidence rate = 1,786 per 100,000 person-years). Tuberculosis was associated with a two-fold elevation in lung cancer risk (HR = 1.97; 95% CI = 1.46–2.65) with significant associations observed for both incident (HR = 2.05; 95% CI = 1.42–2.96) and prevalent tuberculosis (HR = 1.82; 95% CI = 1.09–3.02). Lung cancer risk was greatest in the 2-year window after tuberculosis diagnosis (HR = 5.01; 95% CI = 2.96–8.48) but remained elevated at longer latencies (HR = 1.53; 95% CI = 1.07–2.20). Though tuberculosis was associated with an increased risk of squamous cell carcinoma (HR = 3.71), adenocarcinoma (HR = 1.71), small cell carcinoma (HR = 1.72), and lung cancer of other (HR = 1.23) and unknown histologies (HR = 1.35), only the association for squamous cell carcinoma was statistically significant.

Conclusions: Tuberculosis is associated with increased lung cancer risk in male smokers.

Impact: Our results add to the growing body of evidence implicating chronic inflammation and pulmonary scarring in the etiology of lung cancer. Cancer Epidemiol Biomarkers Prev; 20(4); 672–8. ©2011 AACR.
U.S. Geographic Distribution of Prevaccine Era Cervical Cancer Screening, Incidence, Stage, and Mortality
Authors: Horner Marie-Josèphe , Altekruse Sean F. , Zou Zhaohui , Wideroff Louise , Katki Hormuzd A. , Stinchcomb David G.
Published: March 2011

Background: Cervical cancer prevention programs are being reconfigured to incorporate human papillomavirus (HPV) testing and vaccination. To define priority areas for prevention efforts, we examined the geographic distribution of cervical cancer screening, incidence, stage, and mortality in the United States, prior to the introduction of HPV-based prevention technologies.

Methods: County-level cervical cancer incidence data from 37 central registries were obtained from Surveillance, Epidemiology, and End Results and North American Association of Central Cancer Registries. A spatial–temporal model that accounted for demographic and behavioral attributes was used to generate a complete view of county-level incidence from 1995 to 2004, including counties with missing data. Distribution of stage at diagnosis was examined by registry. Counties with high mortality and infrequent screening were identified using vital statistics and newly available county-level screening estimates.

Results: Compared with non-Hispanic whites and Asian and Pacific Islanders, incidence rates were higher among non-Hispanic black, American Indian and Alaska Native, and Hispanic women. Counties with infrequent screening often experienced elevated incidence and mortality rates and were located in states with suboptimal stage at diagnosis profiles. Affected areas included Appalachia, the southeastern Atlantic states, and the lower Mississippi Valley. Elevated death rates were experienced in central counties of large metropolitan areas.

Conclusions: Geographic and racial/ethnic variability were evident in cervical cancer incidence and mortality. Women living in areas with endemic poverty would benefit from access to HPV-based prevention technologies.

Impact: These findings provide a baseline for monitoring progress in cervical cancer control in the era of HPV-based prevention. Cancer Epidemiol Biomarkers Prev; 20(4); 591–9. ©2011 AACR.
Jewish Ethnicity and Pancreatic Cancer Mortality in a Large U.S. Cohort
Authors: Eldridge Ronald C. , Gapstur Susan M. , Newton Christina C. , Goodman Michael , Patel Alpa V. , Jacobs Eric J.
Published: March 2011

Background: An association between Jewish ethnicity and pancreatic cancer risk was suggested by analyses comparing pancreatic cancer mortality rates between Jews and non-Jews in New York in the 1950s. These analyses lacked information on potential confounding factors and the association between Jewish ethnicity and pancreatic cancer has not been examined in any contemporary U.S. population or in any cohort study.

Methods: We examined the association between Jewish ethnicity and pancreatic cancer mortality among approximately 1 million participants in the Cancer Prevention Study II cohort. Participants completed a questionnaire at enrollment in 1982 which included information on religion, smoking, obesity, and diabetes. During follow-up through 2006, there were 6,727 pancreatic cancer deaths, including 480 among Jewish participants. Proportional hazards modeling was used to calculate multivariable rate ratios (RR).

Results: After adjusting for age, sex, smoking, body mass index, and diabetes, pancreatic cancer mortality was higher among Jewish participants than among non-Jewish whites (RR = 1.43; 95% CI, 1.30–1.57). In analyses by birthplace, RRs were 1.59 (95% CI, 1.31–1.93) for North American–born Jews with North American–born parents, 1.43 (95% CI, 1.27–1.61) for North American–born Jews with 1 or more parents born outside North America, and 1.03 (0.73, 1.44) for Jews born outside North America (Pheterogeneity = 0.07).

Conclusions: These results support a higher risk of developing pancreatic cancer among U.S. Jews that is not explained by established risk factors.

Impact: Future studies may clarify the role of specific environmental or genetic factors responsible for higher risk among U.S. Jews. Cancer Epidemiol Biomarkers Prev; 20(4); 691–8. ©2011 AACR.
Serum Lycopene Concentration and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial
Authors: Kristal Alan R. , Till Cathee , Platz Elizabeth A. , Song Xiaoling , King Irena B. , Neuhouser Marian L. , Ambrosone Christine B. , Thompson Ian M.
Published: March 2011

Background: Lycopene has been promoted for prostate cancer prevention, despite the inconsistency of scientific evidence.

Methods: This nested case-control study examined whether serum lycopene was associated with prostate cancer risk among participants in the Prostate Cancer Prevention Trial, a placebo-controlled trial of finasteride for prostate cancer prevention. Presence or absence of cancer was determined by prostate biopsy, recommended during the trial due to elevated prostate specific antigen (PSA) level or abnormal digital rectal examination (DRE) and offered to all men at the trial end. There were 1,683 cases (461 Gleason score ≥ 7, 125 Gleason score ≥ 8) and 1,751 controls.

Results: There were no associations of lycopene with prostate cancer risk. The odds ratios for a linear increase in lycopene (per 10 μg/dL) were 0.99 (95% CI: 0.94–1.04), 1.01 (0.94–1.08), and 1.02 (0.90–1.15) for Gleason 2 to 6, 7 to 10, and 8 to 10, respectively. In the placebo arm, a 10 μg/dL increase in lycopene was associated with a 7% (95% CI: 14–0) reduced risk of cancer diagnosed following an elevated PSA or abnormal DRE, which are cancers that best match those detected in screened populations. However, a 10 μg/dL increase in lycopene was also associated with an 8% (95% CI: 1–16) increased risk of cancer diagnosed without a biopsy prompt, which are cancers generally not detected. These findings were similar for low- and high-grade cancer.

Conclusion: This study does not support a role for lycopene in prostate cancer prevention.

Impact: Scientists and the public should understand that early studies supporting an association of dietary lycopene with reduced prostate cancer risk have not been replicated in studies using serum biomarkers of lycopene intake. Recommendations of professional societies to the public should be modified to reflect the likelihood that increasing lycopene intake will not affect prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 20(4); 638–46. ©2011 AACR.
Vitamin D: Marker or Mechanism of Action?
Authors: Jacobs Elizabeth T. , Martínez María Elena , Jurutka Peter W.
Published: March 2011

The field of vitamin D and cancer research has been moving forward quickly. However, some challenges remain regarding the interpretation and integration of data collected from epidemiological investigations and laboratory experiments. These include consideration of vitamin D biology, a better understanding of characteristics that affect concentrations of the biomarker of vitamin D status, 25(OH)D, and elucidation of variation in response to vitamin D supplementation. To further the field of vitamin D and cancer prevention, future studies will need to bridge the gap between the epidemiology and molecular biology of vitamin D activity in carcinogenesis. Cancer Epidemiol Biomarkers Prev; 20(4); 585–90. ©2011 AACR.
Plasma Coenzyme Q10 Levels and Prostate Cancer Risk: The Multiethnic Cohort Study
Authors: Chai Weiwen , Cooney Robert V. , Franke Adrian A. , Caberto Christian P. , Wilkens Lynne R. , Le Marchand Loïc , Goodman Marc T. , Henderson Brian E. , Kolonel Laurence N.
Published: March 2011

Background: Coenzyme Q10 (CoQ10) is considered to be a potential anticancer agent, but epidemiologic evidence regarding CoQ10 and prostate cancer risk is lacking. We examined the association of circulating CoQ10 levels with prostate cancer risk, using prediagnostic blood samples.

Methods: Each of the 307 cases was individually matched to approximately 2 controls, for a total of 596 controls, on age, ethnicity, geographic location, date/time of specimen collection, and hours of fasting. Logistic regression was used to compute ORs and 95% CIs.

Results: There was no overall statistically significant association of plasma CoQ10 levels with prostate cancer risk (Ptrend = 0.50). However, after matched sets in which controls who had possible undiagnosed prostate cancer (prostate specific antigen value >4.0) were excluded, the ORs for quintiles 2 to 5 were all less than 1.0.

Conclusions: The results suggest the possibility that moderate levels of circulating CoQ10 may be optimal for the reduction of prostate cancer risk; however, the findings were weak and not statistically significant. Because this is the first epidemiologic study of the association between CoQ10 and prostate cancer, further research on this topic is needed.

Impact: If a nutritional factor such as CoQ10 were determined to reduce prostate cancer risk, it would have considerable public health significance because of the very high incidence of this cancer. Cancer Epidemiol Biomarkers Prev; 20(4); 708–10. ©2011 AACR.
Nutrients, Food Groups, Dietary Patterns, and Risk of Pancreatic Cancer in Postmenopausal Women
Authors: Inoue-Choi Maki , Flood Andrew , Robien Kim , Anderson Kristin
Published: March 2011

Introduction: Identifying modifiable risk factors for pancreatic cancer is important because of its poor prognosis. Previous findings on diet are inconsistent.

Methods: Associations between intake of nutrients, food groups, dietary patterns, and pancreatic cancer risk were examined among 34,642 postmenopausal women in the Iowa Women's Health Study (IWHS).

Results: No significant associations were observed between intake of nutrients and food groups or dietary patterns and pancreatic cancer.

Conclusion: Our findings do not support the hypothesis that fruits, vegetables, and red meat are associated with risk of pancreatic cancer.

Impact: Dietary intake, assessed in multiple aspects in a large prospective cohort study, was not associated with pancreatic cancer. Cancer Epidemiol Biomarkers Prev; 20(4); 711–4. ©2011 AACR.
The Association between Prognostic Demographic and Tumor Characteristics of Breast Carcinomas with Serum 25-OH Vitamin D Levels
Authors: Peppone L , Rickles A , Huston A , Sprod L , Hicks D , Mustian K , Skinner K
Published: March 2011

Objective: Epidemiologic studies show that women with low 25-OH vitamin D levels have an increased risk of breast cancer incidence and mortality. However, there is a lack of research examining vitamin D levels and prognostic variables in breast cancer patients. The aim of this study is to identify the associations between 25-OH vitamin D levels, demographic variables, and prognostic pathological and genetic characteristics of breast cancers.

Method: This study cohort consists of 155 women who underwent breast cancer surgery at the University of Rochester between 1/2009 and 9/2010. Vitamin D levels were obtained in the 1-year period before and after surgery (74% of vitamin D levels within 6 months). Prognostic variables included age, race, menopausal status, Oncotype DX score, TNM staging, ER/PR status, and HER2 expression. ANCOVA, linear regression, and logistic regression were used to determine the association between prognostic variables and 25-OH vitamin D levels, while controlling for relevant covariates (age, race, and month of blood draw).

Results: Non-Caucasian (OR = 3.8; P < 0.01) and premenopausal (OR = 3.5; P < 0.01) breast cancer patients were significantly more likely to have suboptimal 25-OH vitamin D levels than Caucasian and postmenopausal patients, respectively. Women with invasive breast tumors were more likely to have suboptimal vitamin D levels (invasive OR = 2.4; P = 0.10) and lower mean 25-OH vitamin D levels (invasive: 30.5 ng/mL vs. in situ: 36.9 ng/mL; P = 0.04). A significant correlation (r = −0.42; P = 0.04) between decreasing vitamin D levels and increasing Oncotype score was noted. Breast cancer patients who had ER- and triple-negative breast tumors were more likely to have suboptimal levels of 25-OH vitamin D (ER-OR = 2.4; P = 0.07; triple-negative OR = 2.6; P = 0.09).

Conclusions: Breast cancer patients with suboptimal vitamin D levels were more likely to have tumors with more aggressive tumor profiles, worse prognostic markers (ER- and triple-negative tumors), and higher recurrence risk (Oncotype scores), lending support to previous research that found decreased breast cancer survival among vitamin D deficient individuals. Further research is needed to elucidate the biological relationship between vitamin D and prognostic breast cancer markers.
The Association of Serum Phthalates and Parabens with Mammographic Breast Density
Authors: Sprague B , Trentham-Dietz A , Hedman C , Hemming J , Hampton J , Buist D , Aiello Bowles E , Burnside E , Sisney G
Published: March 2011

Humans are exposed to a large number of environmental chemicals which have estrogenic activity, raising concern regarding potential effects on breast tissue and breast cancer risk. Phthalates are commonly found in personal care products, such as shampoos, lotions, and shaving products, and are present in many consumer plastics, adhesives, detergents, and pharmaceuticals. Parabens are also found in personal care products, and are additionally used as antimicrobials in foods. In vitro studies have demonstrated that many phthalates and parabens can bind to the estrogen receptor and initiate estrogenic cellular pathways, and a recent case-control study found that urinary concentrations of mono-ethyl-phthalate were positively associated with breast cancer risk. We examined the cross-sectional association of circulating serum levels of phthalates and parabens with mammographic breast density (a marker for breast cancer risk). A total of 261 postmenopausal women (ages 55–70, with no history of postmenopausal hormone use) were recruited from mammography clinics in Madison, Wisconsin. Patients completed a questionnaire regarding known breast cancer risk factors and provided a blood sample that was analyzed for mono-ethyl-phthalate, mono-butyl-phthalate, mono-benzyl-phthalate, butyl paraben, and propyl paraben. Percent breast density was measured from patients' mammograms as a continuous variable using a computer-assisted thresholding method (Cumulus software). After adjusting for age and body mass index, mono-ethyl-phthalate was positively associated with percent breast density. Women with detectable mono-ethyl-phthalate levels (>0.4 ng/mL; N = 36) had higher percent breast density than women with no detectable mono-ethyl-phthalate (N = 225) in their serum (16.8% vs. 12.8%; P = 0.03). Serum levels of mono-butyl-phthalate and mono-benzyl-phthalate were generally below the limits of detection. Serum levels of butyl-paraben and propyl-paraben were higher (detectable in 55% and 67% of patients, respectively), but neither was associated with breast density (P > 0.20). These results suggest that further investigation into the potential influence of mono-ethly-phthalate (and its parent compound diethyl-phthalate) on breast tissue is warranted.
Cervical Cancer Screening Efficacy in Older Women
Authors: Kamineni A , Weinmann S , Shy KK , Mandelson MT , Glass AG , Weiss NS
Published: March 2011

Although the effectiveness of cervical cancer screening, by means of the Pap smear, has been firmly established in reproductive-age women, the usefulness of cytologic screening in older women is unclear. We sought to assess the degree to which such screening in older women can reduce the incidence of cervical cancer. We conducted a case-control study to evaluate the efficacy of cervical cancer screening in older women enrolled in one of two large health maintenance organizations in the northwestern United States. Cases (n = 69) consisted of those women, 55 to 79 years of age, who were diagnosed with invasive cervical cancer during 1980 to 1999 as enumerated by regional cancer registries. Controls (n = 208) were women sampled from among enrollees who had not previously had a hysterectomy and were similar to cases in terms of age and length of enrollment in the health plan. We reviewed medical records to ascertain demographic, reproductive, and cervical screening history information during the 7 years before the reference date. Only tests which occurred during the presumed detectable preinvasive phase (DPP) of the disease, when screening could be beneficial, were considered and we evaluated results for a series of plausible estimates of this interval. Compared to cases, controls were more likely to have had a Pap test during the DPP, regardless of the estimate used. After adjustment for age and current smoking status, screening was associated with a substantial reduction in the risk of invasive cervical cancer (DPP = 72 months: OR, 0.23; 95% CI, 0.11–0.44). We observed only small differences in the odds ratio across the various estimates of the DPP that were employed. Analysis of the relative incidence of invasive cervical cancer in relation to the time following a negative screening test suggested a large reduction during the first year (OR, 0.09; 95% CI, 0.03–0.24). The incidence remained low for several years thereafter, returning to the incidence among unscreened women after 5 to 7 years. Cervical cancer screening is highly efficacious in older women. This needs to be explicitly considered in weighing the benefits and costs of such screening beyond the reproductive years.
MicroRNA-Related Genetic Variants as Predictors of Early Stage Non–Small Cell Lung Cancer Clinical Outcomes
Authors: Pu X , Lu C , Stewart DJ , Gu J , Hildebrandt MAT , Lin J , Lippman SM , Xifeng W
Published: March 2011

Purpose: MicroRNAs (miRNA) can function as oncogenes or tumor suppressors. In this study, we test the hypothesis that genetic variation within miRNA processing genes or miRNA binding sites in cancer-related genes may alter clinical outcomes for non–small cell cancer (NSCLC) patients.

Methods: We genotyped 72 single nucleotide polymorphisms (SNPs) from eight miRNA processing genes and 168 SNPs from 133 predicted miRNA binding sites in 535 patients with early stage (stages I, IIA, and IIB) NSCLC to determine the effect of these variations on progression risk and overall survival. We further conducted a subset analysis to exclude potential bias due to different treatment regimens.

Results: In the analysis of overall survival, an FAS SNP remained significant for decreased risk after multiple comparisons in all early patients (HR: 0.59, 95% CI: 0.44–0.77; GG: MST = 58 mos, GA + AA: MST = 118 mos) and surgery plus chemotherapy subgroup (HR: 0.19, 95% CI: 0.07–0.46, P = 1.84 × 10−5; GG: MST = 65 mos, GA + AA: MST = 137 mos). In the surgery-only patients, an FZD4 SNP (HR: 0.46, 95% CI: 0.32–0.65; GG: MST = 59 mons, GA + AA: MST = 117 mos) had a significant protective effect after multiple comparisons adjustment. For progression risk, following multiple comparison, an SP1 SNP (HR: 2.19, 95% CI: 1.45–3.32; GG: MST > 270 mos, GA + AA: MST = 45 mos) and an MBD1 SNP (HR: 2.41, 95% CI: 1.45–4.0; AA: MST > 270 mos, C + CC: MST = 90 mos) remained significant increased progression risk in the entire and surgery only population respectively. All the associations significant after adjusting for multiple comparisons were validated by Bootstrap resampling method. A strong cumulative effect of these variant genotypes to increase risk and dramatically decrease median event-free time was consistently observed. We also identified potential higher-order gene–gene interactions among these SNPs.

Conclusions: We identified significant association between miRNA-related genetic variants and early stage NSCLC patient clinical outcomes. With validation, our result can be used in the prognosis of clinical outcomes for early stage NSCLC patients.
The Impact of Detection and Treatment of Carcinoma In Situ on Breast Cancer Mortality
Authors: Trentham-Dietz A , Sprague BL , Alagoz O , Reaidi P , Rosenberg M , Gangnon RE , Stout NK
Published: March 2011

Purpose: Ductal carcinoma in situ (DCIS), a nonobligate precursor to invasive breast cancer, makes up 20% of new breast cancer diagnoses. DCIS is primarily detected by mammography and has excellent prognosis regardless of therapy choice. We aim to quantify the impact of detection and treatment of DCIS on breast cancer mortality using computer modeling.

Methods: We used a validated microsimulation model to replicate U.S. trends in breast cancer incidence and mortality from 1975 to 2000. All breast cancer tumors began in the in situ stage and progressed through more advanced stages with increasing tumor size and lymph node involvement, with a fraction of tumors assumed as nonlethal. Age-adjusted breast cancer mortality was examined under historical U.S. screening and treatment patterns and three alternative scenarios: (1) only women 50 years and older received screening and all breast cancer cases received treatment according to historical patterns, (2) all women received screening according to historical patterns but DCIS was untreated unless later detected at an invasive stage, and (3) historical screening was used but DCIS was never treated.

Results: The model predicts breast cancer mortality rates declined during the 1990s to a low of 39.9 per 100,000 in 2000, which is consistent with observed mortality based on the SEER program (38.0 per 100,000 in 2000). Delaying mammography until age 50 or postponing treatment until DCIS progressed to invasive cancer increased mortality to 42.4 and 43.2 per 100,000, respectively, by 2000. If DCIS patients did not receive any treatment, mortality remained steady (∼51.2 per 100,000) through 2000.

Conclusions: Our model results suggested detection and treatment of DCIS in the U.S. reduced breast cancer deaths in the year 2000 by about 28%. Most of this benefit (92%–94%) could also be achieved if instead mammography began at age 50 or treatment was reserved for invasive breast cancers only.
Perceived Treatment Assignment and Smoking Cessation in a Clinical Trial of Bupropion
Authors: Buchanan TS , Cox LS , Nollen NL , Thomas JL , Berg CJ , Mayo MS , Ahluwalia JS
Published: March 2011

Research on tobacco cessation pharmacotherapy often relies on double-blind, placebo-controlled randomized trials. These studies are designed to control for the placebo effect (i.e., the influence of participants' expectations on treatment outcome). Psychoactive effects of smoking cessation medications such as bupropion may allow participants to correctly guess their treatment assignment at rates greater than chance. Perceived treatment assignment could potentially impact smoking cessation rates. The aim of this study was to determine the impact of perceived treatment assignment on end-of-treatment cotinine-verified smoking abstinence among African-American light smokers [≤10 cigarettes per day (cpd)] enrolled in a double-blind, placebo-controlled study of bupropion. Participants were randomized to bupropion (150 mg bid) or placebo and received identical written materials and health education counseling. Participants (n = 390) included in this study reported their perceived treatment assignment on the end-of-treatment (week 7) survey. They were predominantly female (63.1%), 48.1 years (SD = 11.2), and smoked 8 cpd (SD = 2.5). The majority (81.3%) smoked menthol cigarettes. Participants given bupropion were more likely to correctly guess their treatment assignment (69%; 140/203) than those assigned to placebo (51.3%; 96/187). Quit rates by treatment assignment were 31.5% (bupropion) versus 13.9% (placebo) (OR = 2.78, 95% CI 1.61–5.43, P < 0.01). After adjusting for treatment, participants who perceived assignment to bupropion versus placebo were not more likely to be abstinent (OR = 1.37; 95% CI 0.71–2.64, P = 0.35).The interaction between treatment and perceived treatment assignment was also nonsignificant. Consistent with two previous studies with bupropion, there was evidence of blinding failure for the treatment group. However, in our study, perceived treatment assignment did not significantly impact cotinine-verified cessation outcome at end-of-treatment (week 7). These findings suggest that the role of perceived treatment assignment on smoking cessation with bupropion may differ for light smokers compared to heavier smokers (>10 cpd) sampled in the two earlier studies. Current findings might indicate that expectations of pharmacotherapy are less salient for light smokers.