Publications by authors named "Victoria Cortessis"

69 Publications

Marijuana use and perinatal outcomes in obstetric patients at a safety net hospital.

Eur J Obstet Gynecol Reprod Biol 2021 Sep 16;266:36-41. Epub 2021 Sep 16.

Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Objective: To characterize the association between antepartum marijuana exposure and maternal and neonatal outcomes at our institution.

Study Design: Retrospective chart review identified an obstetric cohort of singleton gestations. Women with self-reported marijuana use were compared with non-users. Demographic characteristics, risk factors, and maternal-fetal outcomes were evaluated. Associations between outcomes and marijuana use were assessed with regression analysis.

Results: Of 2792 deliveries, 5.4% reported marijuana use. Compared to non-users, marijuana users entered prenatal care later, were younger, non-Hispanic, and used other illicit substances. Marijuana users had a higher rate of cesarean delivery (p = 0.01). After adjusting for confounders, marijuana use remained associated with 4.1-fold risk of delivering a small for gestational age (SGA) infant and 2.89-fold risk of neonatal oxygen use.

Conclusion: At a safety net hospital, antepartum marijuana use is significantly associated with cesarean delivery, SGA and supplemental oxygen use at birth. Healthcare disparities associated with marijuana use make this a population of critical interest.
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http://dx.doi.org/10.1016/j.ejogrb.2021.09.015DOI Listing
September 2021

Identification of 22 susceptibility loci associated with testicular germ cell tumors.

Nat Commun 2021 07 23;12(1):4487. Epub 2021 Jul 23.

Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95 percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation.
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http://dx.doi.org/10.1038/s41467-021-24334-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302763PMC
July 2021

What is the optimal timing of intracytoplasmic sperm injection (ICSI) after EGG retrieval? A randomized controlled trial.

J Assist Reprod Genet 2021 Aug 3;38(8):2151-2156. Epub 2021 Jun 3.

Keck School of Medicine, The University of Southern California, 2020 Zonal Avenue Room 534, Los Angeles, CA, 90033, USA.

Purpose: To determine if oocyte denudation and ICSI at 36.5 versus 39 h post HCG and/or Lupron trigger (2.5 h versus 5 h post-oocyte retrieval) influences fertilization and blastulation rates in good prognosis couples METHODS: We performed a prospective, randomized controlled trial of 12 patients undergoing IVF with ICSI at an academic fertility center, resulting in 206 MII oocytes analyzed. At time of retrieval, patients with more than 10 oocytes retrieved had their oocytes randomized into two groups-one group for oocyte denudation and ICSI at 36.5 h post HCG and/or Lupron trigger and the other group for these procedures at 39 h post HCG and/or Lupron trigger (2.5 and 5 h after oocyte retrieval). Primary outcomes were fertilization and blastulation rates.

Results: No difference was observed in fertilization rate, total blastulation rate, or day of blastulation based on timing of denudation and ICSI (all p > 0.05). Multiple regression analyses for fertilization and blastulation controlling for age and BMI revealed no difference in fertilization based on time of ICSI (p = 0.38, 0.71, respectively). A conditional logistic regression to account for multiple oocytes derived from each patient also found no difference in fertilization or blastulation based on timing of ICSI, even when controlling for age and BMI (p = 0.47, 0.59, respectively).

Conclusion(s): In good prognosis couples, we observed no difference in fertilization or blastulation rates based on timing of ICSI within the currently accepted 2- to 6-h window post-retrieval based on a 34-h trigger. The oocyte appears to have a physiological tolerance for fertilization during this window of time, and variability in the timing of ICSI during this window is unlikely to have an impact on cycle outcome.
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http://dx.doi.org/10.1007/s10815-021-02216-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417178PMC
August 2021

Incident testicular cancer in relation to using marijuana and smoking tobacco: A systematic review and meta-analysis of epidemiologic studies.

Urol Oncol 2020 07 12;38(7):642.e1-642.e9. Epub 2020 May 12.

Department of Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA; Department of Obstetrics and Gynecology, Keck School of Medicine of USC, Los Angeles, CA. Electronic address:

Background: Recent epidemiologic studies identified credible associations between marijuana smoking and risk of nonseminomatous testicular germ cell tumors (TGCTs), but did not distinguish exposure to cannabinoid compounds from exposure to other constituents of smoke.

Methods: We implemented a systematic review of scholarly literature followed by random effects meta-analysis to quantitatively synthesize published data relating incident TGCT to each of 2 exposure histories: ever using marijuana, and ever smoking tobacco.

Results: We identified four epidemiologic studies of marijuana use and 12 of tobacco smoking. Summary data concur with earlier reports of a specific association of marijuana use with nonseminoma, summary odds ratio [sOR] = 1.71 (95% confidence interval [CI] 1.12-2.60), and identify a positive association, sOR = 1.18 (95% CI 1.05-1.33), between tobacco smoking and all TGCT.

Conclusions: Available data accord with positive associations between incident TGCT and each exposure, implicating both cannabinoid compounds and other constituents of smoke. Etiologic interpretation awaits epidemiologic studies that assess associations between tobacco smoking and nonseminomatous TGCT, investigating not only these exposures but also both co-use of tobacco and marijuana and smoke-free sources of cannabinoids, while adequately evaluating potential confounding among all of these exposures.
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http://dx.doi.org/10.1016/j.urolonc.2020.03.013DOI Listing
July 2020

A Systematic Review of the Efficacy of Preclinical Models of Lung Cancer Drugs.

Front Oncol 2020 23;10:591. Epub 2020 Apr 23.

Department of Medical Oncology, Norris Comprehensive Cancer Center, Los Angeles, CA, United States.

Preclinical cell models are the mainstay in the early stages of drug development. We sought to explore the preclinical data that differentiated successful from failed therapeutic agents in lung cancer. One hundred thirty-four failed lung cancer drugs and twenty seven successful lung cancer drugs were identified. Preclinical data were evaluated. The independent variable for cell model experiments was the half maximal inhibitory concentration (IC50), and for murine model experiments was tumor growth inhibition (TGI). A logistic regression was performed on quartiles (Q) of IC50s and TGIs. We compared odds of approval among drugs defined by IC50 and TGI quartile. Compared to drugs with preclinical cell experiments in highest IC50 quartile (Q4, IC50 345.01-100,000 nM), those in Q3 differed little, but those in the lower two quartiles had better odds of being approved. However, there was no significant monotonic trend identified (P-trend 0.4). For preclinical murine models, TGI values ranged from -0.3119 to 1.0000, with a tendency for approved drugs to demonstrate poorer inhibition than failed drugs. Analyses comparing success of drugs according to TGI quartile produced interval estimates too wide to be statistically meaningful, although all point estimates accord with drugs in Q2-Q4 (TGI 0.5576-0.7600, 0.7601-0.9364, 0.9365-1.0000) having lower odds of success than those in Q1 (-0.3119-0.5575). There does not appear to be a significant linear trend between preclinical success and drug approval, and therefore published preclinical data does not predict success of therapeutics in lung cancer. Newer models with predictive power would be beneficial to drug development efforts.
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http://dx.doi.org/10.3389/fonc.2020.00591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190806PMC
April 2020

Role of sex steroid hormones in pelvic organ prolapse.

Menopause 2020 08;27(8):941-951

Department of Obstetrics and Gynecology, Keck School of Medicine of the University of Southern California.

Objective: Pelvic organ prolapse (POP) affects a significant percentage of women and contributes to major healthcare costs both in the United States and worldwide. This review examines the current understanding of the role of sex steroid hormones (estrogens, androgens, and progesterone) in POP in premenopausal, perimenopausal, and postmenopausal women.

Methods: We reviewed the relevant studies on POP related to estrogens, androgens, and progesterone in both animal models and humans.

Results: Estrogen has a profound influence on the synthesis and metabolism of pelvic connective tissues, and may have the ability to both prevent POP and improve prognosis if used therapeutically. There is limited research regarding the role of androgens and progesterone and their receptors in POP and results so far have been contradictory, warranting further study to determine whether changes in androgen and progesterone receptor expression are a cause or effect of POP.

Conclusions: Because of the role that estrogen plays in maintaining the integrity of pelvic floor connective tissues, we propose that rigorous and well-controlled studies are needed on the role of exogenous estrogen administration as a form of POP prevention. : Video Summary:http://links.lww.com/MENO/A583.
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http://dx.doi.org/10.1097/GME.0000000000001546DOI Listing
August 2020

Neonatal hypoglycemia after initiation of late preterm antenatal corticosteroids.

J Perinatol 2020 09 14;40(9):1339-1348. Epub 2020 Feb 14.

Division of Neonatology, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Objective: To compare the frequency and severity of neonatal hypoglycemia in pregnancies treated with and without late preterm antenatal corticosteroids.

Study Design: We conducted a retrospective cohort study of late preterm deliveries at LAC + USC (2015-2018). Neonatal outcomes were compared between pregnancies treated with and without corticosteroids.

Results: 93 pregnancies (39.9%) received corticosteroids and 140 (60.1%) did not. Neonates born to women given corticosteroids were more likely to be hypoglycemic (47.3 vs. 29.3%, OR 2.25, p = 0.01). The mean initial glucose (45.6 mg/dL vs. 51.9 mg/dL, p = 0.01) and glucose nadir (39.1 mg/dL vs. 45.4 mg/dL, p < 0.001) were significantly lower if the neonates received corticosteroids. Neonates admitted to the NICU solely for hypoglycemia were more likely to be born to women treated with corticosteroids (OR 4.71, p = 0.01).

Conclusion: Administration of late preterm corticosteroids was associated with an increased incidence and severity of neonatal hypoglycemia.
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http://dx.doi.org/10.1038/s41372-020-0589-1DOI Listing
September 2020

Non-prescription cannabis use for symptom management amongst women with gynecologic malignancies.

Gynecol Oncol Rep 2019 Nov 9;30:100497. Epub 2019 Sep 9.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecologic, University of Southern California, Los Angeles, CA, USA.

Objectives: To evaluate interest in and patterns of use of non-prescription cannabis products for symptom management amongst gynecologic cancer patients living in states with legal access to medical and recreational marijuana.

Methods: Cross-sectional study using a novel 35-question survey distributed to women diagnosed with gynecologic cancer within two academic centers in California and Colorado. The survey queries demographic and disease traits, and both objective and subjective issues surrounding use of cannabis products for symptom management. Surveys were distributed to patients actively receiving treatment or under surveillance.

Results: Enrollment began July 16, 2018 and was completed December 1, 2018. Survey return rate was 52.7%. A total of 225 participants met inclusion criteria.Sixty-two percent reported that they have used or would be interested in using cannabis products for symptom management; 60 (26.7%) are using non-prescription cannabis for treatment of cancer related symptoms, and 80 (35.6%) are interested in using cannabis derivatives under direction of their oncologist. Reasons cited for use of cannabis included: pain control (n = 41, 68.3), insomnia (n = 33, 55.0%), anxiety (n = 29, 48.3%), nausea (n = 26, 43.3%), and appetite stimulation (n = 21, 35.0%). Of the women using cannabis products, almost half report decreased prescription narcotic use after initiation of cannabis products (n = 27, 45.0%).

Conclusions: Women with gynecologic cancer report a strong interest in the use of non-prescription cannabis products for management of cancer-related symptoms. Practitioners in the field of gynecologic oncology should be aware of the frequency of use of non-prescription cannabis amongst their patients as well as the growing desire for guidance about the use of cannabis derivatives. A substantial number of patients report decreased reliance on opioids when using cannabis derivatives for pain control.
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http://dx.doi.org/10.1016/j.gore.2019.100497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804884PMC
November 2019

Dysregulation of Placental Functions and Immune Pathways in Complete Hydatidiform Moles.

Int J Mol Sci 2019 Oct 10;20(20). Epub 2019 Oct 10.

Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

Gene expression studies of molar pregnancy have been limited to a small number of candidate loci. We analyzed high-dimensional RNA and protein data to characterize molecular features of complete hydatidiform moles (CHMs) and corresponding pathologic pathways. CHMs and first trimester placentas were collected, histopathologically examined, then flash-frozen or paraffin-embedded. Frozen CHMs and control placentas were subjected to RNA-Seq, with resulting data and published placental RNA-Seq data subjected to bioinformatics analyses. Paraffin-embedded tissues from CHMs and control placentas were used for tissue microarray (TMA) construction, immunohistochemistry, and immunoscoring for galectin-14. Of the 14,022 protein-coding genes expressed in all samples, 3,729 were differentially expressed (DE) in CHMs, of which 72% were up-regulated. DE genes were enriched in placenta-specific genes (OR = 1.88, = 0.0001), of which 79% were down-regulated, imprinted genes (OR = 2.38, = 1.54 × 10), and immune genes (OR = 1.82, = 7.34 × 10), of which 73% were up-regulated. DNA methylation-related enzymes and histone demethylases were dysregulated. "Cytokine-cytokine receptor interaction" was the most impacted of 38 dysregulated pathways, among which 17 were immune-related pathways. TMA-based immunoscoring validated the lower expression of galectin-14 in CHM. In conclusion, placental functions were down-regulated, imprinted gene expression was altered, and immune pathways were activated, indicating complex dysregulation of placental developmental and immune processes in CHMs.
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http://dx.doi.org/10.3390/ijms20204999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829352PMC
October 2019

Systematic Review and Meta-analysis of Testicular Germ Cell Tumors Following In Utero Exposure to Diethylstilbestrol.

JNCI Cancer Spectr 2019 Sep 28;3(3):pkz045. Epub 2019 Jun 28.

See the Notes section for the full list of authors' affiliations.

Background: Early exposure to estrogen-like compounds has been implicated in the etiology of testicular cancer, but individual level epidemiologic data addressing this hypothesis are scarce. The synthetic estrogen diethylstilbestrol (DES) was administered during pregnancy from 1948 to 1971, but sequelae of in utero exposure have been more extensively characterized in females than in males.

Methods: By systematic review, we sought to identify all epidemiologic research relating testicular cancer to a history of in utero exposure to diethylstilbestrol. Identified studies were critically appraised to assemble a set of nonredundant data in which any in utero exposure to DES was compared between men with incident testicular cancer and cancer-free men. These data were synthesized using random effects meta-analysis to estimate the summary association between in utero DES exposure and testicular cancer.

Results: By meta-analysis of data from the six qualifying studies, the summary odds ratio estimate of the in utero DES-testicular cancer association was 2.98 (95% confidence interval = 1.15 to 7.67).

Conclusions: Results of this comprehensive meta-analysis accord with a threefold increase in testicular cancer risk among men who were exposed in utero to DES, implicating early hormonal exposures in etiology of testicular cancer. Because use of DES ceased in 1971, this work may provide the most comprehensive estimate of this association that will be made.
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http://dx.doi.org/10.1093/jncics/pkz045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748667PMC
September 2019

ASGE guideline on the role of endoscopy in the evaluation and management of choledocholithiasis.

Gastrointest Endosc 2019 06 9;89(6):1075-1105.e15. Epub 2019 Apr 9.

Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA. Electronic address:

Each year choledocholithiasis results in biliary obstruction, cholangitis, and pancreatitis in a significant number of patients. The primary treatment, ERCP, is minimally invasive but associated with adverse events in 6% to 15%. This American Society for Gastrointestinal Endoscopy (ASGE) Standard of Practice (SOP) Guideline provides evidence-based recommendations for the endoscopic evaluation and treatment of choledocholithiasis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to rigorously review and synthesize the contemporary literature regarding the following topics: EUS versus MRCP for diagnosis, the role of early ERCP in gallstone pancreatitis, endoscopic papillary dilation after sphincterotomy versus sphincterotomy alone for large bile duct stones, and impact of ERCP-guided intraductal therapy for large and difficult choledocholithiasis. Comprehensive systematic reviews were also performed to assess the following: same-admission cholecystectomy for gallstone pancreatitis, clinical predictors of choledocholithiasis, optimal timing of ERCP vis-à-vis cholecystectomy, management of Mirizzi syndrome and hepatolithiasis, and biliary stent therapy for choledocholithiasis. Core clinical questions were derived using an iterative process by the ASGE SOP Committee. This body developed all recommendations founded on the certainty of the evidence, balance of risks and harms, consideration of stakeholder preferences, resource utilization, and cost-effectiveness.
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http://dx.doi.org/10.1016/j.gie.2018.10.001DOI Listing
June 2019

Availability of long-acting reversible contraceptives in Los Angeles County clinics through a Medicaid state plan amendment program.

Contraception 2018 12 1;98(6):471-475. Epub 2018 Aug 1.

Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, California; Keck School of Medicine, University of Southern California, Los Angeles, California.

Objective: To assess the availability of long acting reversible contraceptive (LARC) methods in Los Angeles County through providers participating in a California State Medicaid State Plan Amendment Program called Family Planning, Access, Care and Treatment (Family PACT).

Study Design: This was a cross-sectional telephone survey utilizing "secret shopper" methodology. From 855 Family PACT providers in Los Angeles County in 2015, a representative sample of 400 providers was selected for study. Young female researchers posing as potential patients called each sampled clinic to ask a scripted series of questions about LARC availability for Family PACT patients in that practice.

Results: All but one eligible practice (99.7%) responded to our questions. Among the 336 responding practices, 284 said they accepted Family PACT. Of those accepting Family PACT, staff answering the telephone call at 61% said they did not provide any LARC method onsite, 2% provided all currently available LARC methods, and 6% provided same-day placement of any LARC.

Conclusion: The majority of Family PACT practices surveyed said that they did not provide any LARC onsite, and very few provided same-day LARC placement despite easy patient enrollment procedures, relatively reasonable reimbursement and concerted efforts to increase LARC use. Substantial barriers to greater uptake may rest at the provider level with either actual unavailability of LARC or staff perception of unavailability.

Implications: Only a minority of Family PACT practices said that LARC methods were available onsite, which imposes substantial restriction to access for women who are entitled to have access without cost. Other states developing programs should be aware of this challenge.
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http://dx.doi.org/10.1016/j.contraception.2018.07.138DOI Listing
December 2018

Integrated Molecular Characterization of Testicular Germ Cell Tumors.

Cell Rep 2018 06;23(11):3392-3406

The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.

We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance-KIT, KRAS, and NRAS-exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma. Striking differences in global DNA methylation and microRNA expression between histology subtypes highlight a likely role of epigenomic processes in determining histologic fates in TGCTs. We also identified a subset of pure seminomas defined by KIT mutations, increased immune infiltration, globally demethylated DNA, and decreased KRAS copy number. We report potential biomarkers for risk stratification, such as miRNA specifically expressed in teratoma, and others with molecular diagnostic potential, such as CpH (CpA/CpC/CpT) methylation identifying embryonal carcinomas.
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http://dx.doi.org/10.1016/j.celrep.2018.05.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6075738PMC
June 2018

Comprehensive meta-analysis reveals association between multiple imprinting disorders and conception by assisted reproductive technology.

J Assist Reprod Genet 2018 Jun 25;35(6):943-952. Epub 2018 Apr 25.

Department of Preventive Medicine, Keck School of Medicine at USC, 1441 Eastlake Avenue, MC-9175, Los Angeles, CA, 90089-9175, USA.

Purpose: To determine whether a history of conception by assisted reproductive technology (ART) is associated with occurrence of one or more imprinting disorders of either maternal or paternal origin.

Methods: We implemented a systematic review of scholarly literature followed by comprehensive meta-analysis to quantitatively synthesize data from reports relating to use of ART to occurrence of any imprinting disorder of humans, including Beckwith-Wiedemann (BWS), Angelman (AS), Prader-Willi (PWS), and Silver-Russell (SRS) syndromes, as well as transient neonatal diabetes mellitus (TNDB) and sporadic retinoblasoma (RB).

Results: The systematic review identified 13 reports presenting unique data from 23 studies that related conception following ART to occurrence of imprinting disorders. Multiple studies of four disorder were identified, for which meta-analysis yielded the following summary estimates of associations with a history of ART: AS, summary odds ratio (sOR) = 4.7 (95% confidence interval (CI) 2.6-8.5, 4 studies); BWS, sOR = 5.8 (95% CI 3.1-11.1, 8 studies); PWS, sOR = 2.2 (95% CI 1.6-3.0, 6 studies); SRS, sOR = 11.3 (95% CI 4.5-28.5, 3 studies). Only one study reported on each of TNDB and RB.

Conclusion: Published data reveal positive associations between history of ART conception and each of four imprinting disorders. Reasons for these associations warrant further investigation.
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http://dx.doi.org/10.1007/s10815-018-1173-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030010PMC
June 2018

The use of a low-literacy version of the Medicaid sterilization consent form to assess sterilization-related knowledge in Spanish-speaking women: results from a randomized controlled trial.

Contraception 2018 06 26;97(6):546-551. Epub 2018 Mar 26.

Keck School of Medicine, University of Southern California, Los Angeles, California.

Objective: To learn whether a version of the Medicaid Sterilization Consent Form (SCF) adapted for populations of low-literacy can help Spanish-speaking women better understand the process and consequences of tubal sterilization.

Study Design: We randomly assigned Spanish-speaking women, ages 21-45 years, to review either a "standard" or "low-literacy" version of the Medicaid SCF. We assessed sterilization-related knowledge using items from the Postpartum Tubal Sterilization Knowledge questionnaire, using as the primary outcome correct identification of least four or more knowledge items and as secondary outcome participants' preferred version of the SCF.

Results: Overall sterilization-related knowledge was low in both groups, with 33% of women (n=100) who reviewed the standard SCF form and 42% of those who reviewed the low-literacy form (n=100) correctly identifying four or more knowledge-related items (p=.19). Regarding specific items, women in the low-literacy SCF group were more likely than those in the standard SCF group to understand the permanence of sterilization (69% versus 49%, p<.01) and the time requirement between signing the consent document and undergoing sterilization (79% versus 59%, p<.01). The groups were similar in appreciating availability of equally effective nonpermanent contraceptive options (71% versus 64%, p=.29), time from signing to expiration (33% versus 38%, p=.46), or non-binding nature of sterilization consent (55% versus 62%, p=.32). Overall, 71% of participants from both groups preferred the low-literacy form.

Conclusion: In our patient population, characterized by low educational attainment and inadequate health literacy skills, a low-literacy SCF did not improve overall sterilization-related knowledge when compared to the standard SCF. The low-literacy version did improve understanding of the permanence of sterilization and time requirements to undergo the procedure.

Implications: Neither form conveyed an adequate level of knowledge to this vulnerable Spanish-speaking population. Therefore, a considerable need persists for detailed education regarding availability of equally effective reversible contraceptive options, procedure-related risks, and permanence of sterilization throughout the process of informed consent.
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http://dx.doi.org/10.1016/j.contraception.2018.02.005DOI Listing
June 2018

Intrauterine Device Use and Cervical Cancer Risk: A Systematic Review and Meta-analysis.

Obstet Gynecol 2017 12;130(6):1226-1236

Departments of Obstetrics and Gynecology and Preventive Medicine, Keck School of Medicine of USC, and the Suzanne Dworak-Peck School of Social Work, University of Southern California, Los Angeles, California.

Objective: To estimate the association between use of an intrauterine device (IUD) and risk of cervical cancer by subjecting existing data to critical review, quantitative synthesis, and interpretation.

Data Sources: We searched PubMed, Web of Science, ClinicalTrials.gov, and catalogs of scientific meetings and abstracts, theses, and dissertations queried from inception through July 2016.

Methods Of Study Selection: Examination of abstracts from 225 reports identified 34 studies with individual-level measures of use of an IUD and incident cervical cancer. By critically assessing the full text of these reports, independent reviewers identified 17 studies conducted without recognized sources of systematic error, of which 16 could be harmonized for meta-analysis.

Tabulation, Integration, And Results: Point and interval estimates of the association between use of an IUD and incident cervical cancer were extracted from original reports into a structured database along with key features of study design and implementation. A random-effects meta-analysis was implemented to quantitatively synthesize extracted estimates and assess likely influence of publication bias, residual confounding, heterogeneity of true effect size, and human papillomavirus prevalence and cervical cancer incidence in source populations. Women who used an IUD experienced less cervical cancer (summary odds ratio 0.64, 95% CI 0.53-0.77). Neither confounding by recognized risk factors nor publication bias seems a plausible explanation for the apparent protective effect, which may be stronger in populations with higher cervical cancer incidence.

Conclusion: Invasive cervical cancer may be approximately one third less frequent in women who have used an IUD. This possible noncontraceptive benefit could be most beneficial in populations with severely limited access to screening and concomitantly high cervical cancer incidence.
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http://dx.doi.org/10.1097/AOG.0000000000002307DOI Listing
December 2017

Winner's Curse Correction and Variable Thresholding Improve Performance of Polygenic Risk Modeling Based on Genome-Wide Association Study Summary-Level Data.

PLoS Genet 2016 Dec 30;12(12):e1006493. Epub 2016 Dec 30.

Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, United States of America.

Recent heritability analyses have indicated that genome-wide association studies (GWAS) have the potential to improve genetic risk prediction for complex diseases based on polygenic risk score (PRS), a simple modelling technique that can be implemented using summary-level data from the discovery samples. We herein propose modifications to improve the performance of PRS. We introduce threshold-dependent winner's-curse adjustments for marginal association coefficients that are used to weight the single-nucleotide polymorphisms (SNPs) in PRS. Further, as a way to incorporate external functional/annotation knowledge that could identify subsets of SNPs highly enriched for associations, we propose variable thresholds for SNPs selection. We applied our methods to GWAS summary-level data of 14 complex diseases. Across all diseases, a simple winner's curse correction uniformly led to enhancement of performance of the models, whereas incorporation of functional SNPs was beneficial only for selected diseases. Compared to the standard PRS algorithm, the proposed methods in combination led to notable gain in efficiency (25-50% increase in the prediction R2) for 5 of 14 diseases. As an example, for GWAS of type 2 diabetes, winner's curse correction improved prediction R2 from 2.29% based on the standard PRS to 3.10% (P = 0.0017) and incorporating functional annotation data further improved R2 to 3.53% (P = 2×10-5). Our simulation studies illustrate why differential treatment of certain categories of functional SNPs, even when shown to be highly enriched for GWAS-heritability, does not lead to proportionate improvement in genetic risk-prediction because of non-uniform linkage disequilibrium structure.
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http://dx.doi.org/10.1371/journal.pgen.1006493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201242PMC
December 2016

Does the type of progestin influence the production of clotting factors?

Contraception 2017 02 13;95(2):113-116. Epub 2016 Jul 13.

Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA; Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.

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http://dx.doi.org/10.1016/j.contraception.2016.07.007DOI Listing
February 2017

Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry.

Hum Mol Genet 2016 Mar 4;25(6):1203-14. Epub 2016 Jan 4.

Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD, USA.

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.
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http://dx.doi.org/10.1093/hmg/ddv492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817084PMC
March 2016

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types.

J Natl Cancer Inst 2015 Dec 12;107(12):djv279. Epub 2015 Oct 12.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (JNS, OP, SIB, QL, CCA, LTA, JDF, MTL, LM, SAS, PRT, KAM, PR, DA, DB, BAB, AB, LBr, WHC, CCC, JSC, JFFJr, NDF, LEBF, MGC, AMG, RNH, NH, WH, PDI, BTJ, CK, CMK, LML, MSL, LEM, LPO, RSSS, WeiT, MT, CWa, SW, NW, KY, PH, LMM, NEC, NR, DTS, SJC, NC); Information Management Services, Silver Spring, MD (WAW, CG); Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD (MY, ZW, LBu, AH, CLi); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (IDV, KAB, BMB, CoC, MCB, CF, EG, SL, JP, MSt, DJH); Department of Epidemiology, Harvard School of Public Health, Boston, MA (IDV, OA, KAB, CoC, MCB, EG, RSK, SL, JP, HDS, MSt, DTr, DJH, PK); Ontario Health Study, Toronto, Ontario, Canada (MPP); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (HOA, EWe); Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (AA, MF); UCL Cancer Institute, London, UK (MFA, AMF, DH); Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, UK (MFA, AMF, DH, RT); Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China (SJA, JS, YLW, XCZ); Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden (UA, RH, BSM); Division of Urologic Surgery, Washington University School of Medicine, Saint Louis, MO (GAJr, RGIII); Litwin Centre for Cancer Genetics, University of Toronto, Ontario, Canada (ILA, NG, JSW); Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada (ILA, SG, NG, JSW); Hematology Unit, Ospedale Oncologico di Riferimento Regionale A. Businco, Cagliari, Italy (EA); Department of Medicin

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.

Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.

Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.

Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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http://dx.doi.org/10.1093/jnci/djv279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806328PMC
December 2015

The Influence of Screening for Precancerous Lesions on Family-Based Genetic Association Tests: An Example of Colorectal Polyps and Cancer.

Am J Epidemiol 2015 Oct 24;182(8):714-22. Epub 2015 Aug 24.

Unintended consequences of secondary prevention include potential introduction of bias into epidemiologic studies estimating genotype-disease associations. To better understand such bias, we simulated a family-based study of colorectal cancer (CRC), which can be prevented by resecting screen-detected polyps. We simulated genes related to CRC development through risk of polyps (G1), risk of CRC but not polyps (G2), and progression from polyp to CRC (G3). Then, we examined 4 analytical strategies for studying diseases subject to secondary prevention, comparing the following: 1) CRC cases with all controls, without adjusting for polyp history; 2) CRC cases with controls, adjusting for polyp history; 3) CRC cases with only polyp-free controls; and 4) cases with either CRC or polyps with controls having neither. Strategy 1 yielded estimates of association between CRC and each G that were not substantially biased. Strategies 2-4 yielded biased estimates varying in direction according to analysis strategy and gene type. Type I errors were correct, but strategy 1 provided greater power for estimating associations with G2 and G3. We also applied each strategy to case-control data from the Colon Cancer Family Registry (1997-2007). Generally, the best analytical option balancing bias and power is to compare all CRC cases with all controls, ignoring polyps.
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http://dx.doi.org/10.1093/aje/kwv128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4597802PMC
October 2015

The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease.

Cancer Res 2014 Oct;74(20):5808-18

Ramón y Cajal Hospital, Madrid, Spain.

A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) ≥ 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 × 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P(trend) = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models.
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http://dx.doi.org/10.1158/0008-5472.CAN-14-1531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203382PMC
October 2014

Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.

Hum Mol Genet 2014 Dec 15;23(24):6616-33. Epub 2014 Jul 15.

Department of Preventive Medicine, Biostatistics Division, Keck School of Medicine and.

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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http://dx.doi.org/10.1093/hmg/ddu363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240198PMC
December 2014

Validation of Surveillance, Epidemiology, and End Results TNM staging for testicular germ cell tumor.

Urol Oncol 2014 Nov 23;32(8):1341-6. Epub 2014 May 23.

USC Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA. Electronic address:

Objectives: To evaluate the accuracy of testicular germ cell tumor category in the Surveillance, Epidemiology, and End Results (SEER) database following the 2010 American Joint Committee of Cancer revision of the TNM staging criteria.

Methods: We performed a retrospective review of our testicular cancer database from January 2010 to July 2011. Registrar extracted data on 76 patients were entered into the Cancer Surveillance Program database from 2 hospitals. We reviewed the SEER coding for each patient, including T, N, M, and S and overall stage group, as well as the range and S value given for tumor markers (lactate dehydrogenase, beta-human chorionic gonadotropin, and α-fetoprotein) both preorchiectomy and postorchiectomy. We then compared these values with the actual staging and tumor markers determined by patient medical record review by a single urologist.

Results: A high proportion of registry records were found to have inaccurate values of category: 71% of S category entries and 34% of N category entries, leading to an overall group stage inaccuracy of 77% in SEER data. Accuracy of overall combined stage group was significantly different between hospitals, with a higher percentage of errors at Hospital A (P< 0.05).

Conclusion: Despite improvements made to the SEER criteria for extracting data used to code testicular germ cell tumor TNM stage, considerable errors were identified, most notably in tumor marker and nodal status, resulting in an overwhelming number of errors in overall stage. Our findings suggest caution when utilizing SEER data for review of patients with testicular cancer and their staging.
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http://dx.doi.org/10.1016/j.urolonc.2014.04.004DOI Listing
November 2014

Genome-wide interaction study of smoking and bladder cancer risk.

Carcinogenesis 2014 Aug 24;35(8):1737-44. Epub 2014 Mar 24.

Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.

Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 × 10(-) (5) were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20-1.50, P value = 5.18 × 10(-) (7)]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67-0.84, P value = 6.35 × 10(-) (7)). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers-including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer.
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http://dx.doi.org/10.1093/carcin/bgu064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123644PMC
August 2014

Three authors reply.

Am J Epidemiol 2014 Apr 19;179(8):1037. Epub 2014 Mar 19.

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.

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http://dx.doi.org/10.1093/aje/kwu042DOI Listing
April 2014

Comprehensive analyses of DNA repair pathways, smoking and bladder cancer risk in Los Angeles and Shanghai.

Int J Cancer 2014 Jul 13;135(2):335-47. Epub 2014 Jan 13.

Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA.

Tobacco smoking is a bladder cancer risk factor and a source of carcinogens that induce DNA damage to urothelial cells. Using data and samples from 988 cases and 1,004 controls enrolled in the Los Angeles County Bladder Cancer Study and the Shanghai Bladder Cancer Study, we investigated associations between bladder cancer risk and 632 tagSNPs that comprehensively capture genetic variation in 28 DNA repair genes from four DNA repair pathways: base excision repair (BER), nucleotide excision repair (NER), non-homologous end-joining (NHEJ) and homologous recombination repair (HHR). Odds ratios (ORs) and 95% confidence intervals (CIs) for each tagSNP were corrected for multiple testing for all SNPs within each gene using pACT and for genes within each pathway and across pathways with Bonferroni. Gene and pathway summary estimates were obtained using ARTP. We observed an association between bladder cancer and POLB rs7832529 (BER) (pACT = 0.003; ppathway = 0.021) among all, and SNPs in XPC (NER) and OGG1 (BER) among Chinese men and women, respectively. The NER pathway showed an overall association with risk among Chinese males (ARTP NER p = 0.034). The XRCC6 SNP rs2284082 (NHEJ), also in LD with SREBF2, showed an interaction with smoking (smoking status interaction pgene = 0.001, ppathway = 0.008, poverall = 0.034). Our findings support a role in bladder carcinogenesis for regions that map close to or within BER (POLB, OGG1) and NER genes (XPC). A SNP that tags both the XRCC6 and SREBF2 genes strongly modifies the association between bladder cancer risk and smoking.
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http://dx.doi.org/10.1002/ijc.28693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016180PMC
July 2014

Genome-wide association study identifies multiple loci associated with bladder cancer risk.

Hum Mol Genet 2014 Mar 24;23(5):1387-98. Epub 2013 Oct 24.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10(-5) was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10(-9)) and rs907611 on 11p15.5 (P = 4.11 × 10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10(-7)) and rs4510656 on 6p22.3 (P = 6.98 × 10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.
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http://dx.doi.org/10.1093/hmg/ddt519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919005PMC
March 2014

Null association between histology of first and second primary malignancies in men with bilateral testicular germ cell tumors.

Am J Epidemiol 2013 Oct 8;178(8):1240-5. Epub 2013 Aug 8.

Testicular germ cell tumors (TGCTs), the most common neoplasms of young men, are categorized histologically as either seminomas or nonseminomas/mixed germ cell tumors. These subtypes differ by age at diagnosis and clinical course, but little is known about etiological distinctions. To test the hypothesis that histological subtypes have distinct sets of unrecognized etiological factors, we used a recently described approach, estimating the association between histological types of first and second tumors of men with 2 primary TGCTs. The study population of 488 men each with 2 primary TGCTs was ascertained through population-based cancer registries in the United States between 1972 and 2006. Univariate logistic regression analysis revealed that the histology of second primary TGCTs was associated with the histology of first TGCTs (odds ratio = 1.70, 95% confidence interval: 1.14, 2.52); however, the association did not persist in analyses adjusted for age at diagnosis of first TGCT (odds ratio = 1.09, 95% confidence interval: 0.71, 1.70). These results would be expected if the subtypes share etiology but experience different rates of progression to diagnosis or if the histological fate of TGCTs is influenced by age-related processes. Men with 2 primary TGCTs provide novel opportunities to learn whether histological subtypes are likely to share etiology, so results may inform research designed to identify causes.
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http://dx.doi.org/10.1093/aje/kwt100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792726PMC
October 2013

Dietary sources of N-nitroso compounds and bladder cancer risk: findings from the Los Angeles bladder cancer study.

Int J Cancer 2014 Jan 15;134(1):125-35. Epub 2013 Jul 15.

Department of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA.

N-Nitroso compounds (NOCs) have been proposed as possible bladder carcinogens. The main sources of exogenous exposure to NOCs are cigarette smoke and diet, particularly processed (i.e., nitrite-treated) meats. Perhaps more importantly, NOCs can be formed endogenously from dietary precursors such as nitrate, nitrite and amines. Heme has been shown to increase endogenous nitrosation. We examined the role of dietary sources of NOCs and NOC precursors as potential bladder cancer risk factors using data from the Los Angeles Bladder Cancer Study, a population-based case-control study. Dietary and demographic information was collected from 1,660 bladder cancer cases and 1,586 controls via a structured questionnaire. Intake of liver and of salami/pastrami/corned beef, were both statistically significantly associated with risk of bladder cancer in this study, particularly among nonsmokers. Heme intake was also statistically significantly associated with risk of bladder cancer among nonsmokers only. When considering NOC precursors, risk was consistently higher among subjects with concurrent high intake of nitrate and high intake of the different meats (sources of amines and nitrosamines). Results of this study are consistent with a role of dietary sources of NOC precursors from processed meats in bladder cancer risk, suggesting consumption of meats with high amine and heme content such as salami and liver as a risk factor for bladder cancer. In addition, any effect of consuming these meats may be greater when accompanied by high nitrate intake.
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http://dx.doi.org/10.1002/ijc.28331DOI Listing
January 2014
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