Patricia Luhn

National Cancer Institute (USA), Maryland, United States

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Publications (9)29.36 Total impact

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    ABSTRACT: The prognosis of endometrial cancer is strongly associated with stage at diagnosis, suggesting that early detection may reduce mortality. Women who are diagnosed with endometrial carcinoma often have a lengthy history of vaginal bleeding, which offers an opportunity for early diagnosis and curative treatment. We performed DNA methylation profiling on population-based endometrial cancers to identify early detection biomarkers and replicated top candidates in two independent studies. We compared DNA methylation values of 1500 probes representing 807 genes in 148 population-based endometrial carcinoma samples and 23 benign endometrial tissues. Markers were replicated in another set of 69 carcinomas and 40 benign tissues profiled on the same platform. Further replication was conducted in The Cancer Genome Atlas and in prospectively collected endometrial brushings from women with and without endometrial carcinomas. We identified 114 CpG sites showing methylation differences with p-values of ≤10(-7) between endometrial carcinoma and normal endometrium. Eight genes (ADCYAP1, ASCL2, HS3ST2, HTR1B, MME, NPY, and SOX1) were selected for further replication. Age-adjusted odds ratios for endometrial cancer ranged from 3.44 (95%-CI: 1.33-8.91) for ASCL2 to 18.61 (95%-CI: 5.50-62.97) for HTR1B. An area under the curve (AUC) of 0.93 was achieved for discriminating carcinoma from benign endometrium. Replication in The Cancer Genome Atlas and in endometrial brushings from an independent study confirmed the candidate markers. This study demonstrates that methylation markers may be used to evaluate women with abnormal vaginal bleeding to distinguish women with endometrial carcinoma from the majority of women without malignancy. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 03/2014; · 6.20 Impact Factor
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    ABSTRACT: The National Cancer Institute Principles and Practice of Cancer Prevention and Control course is a 4-week course encompassing a variety of cancer prevention and control topics that is open to attendees from medical, academic, government, and related institutions around the world. Themes related to the challenges health disparities present to cancer prevention efforts and potential solutions to these issues emerged from facilitated group discussions among the 2012 course participants. Small-group discussion sessions with participants (n = 85 from 33 different countries) and facilitators (n = 9) were held once per week throughout the 4-week course. Facilitators prepared open-ended questions related to course topics. Participants provided responses reflecting their opinions of topics on the basis of experiences in their countries. A thematic analysis was conducted to explore themes emerging from the discussion groups. The varied influences of health disparities on cancer prevention efforts among > 30 countries represented prominent themes across discussion groups. Participants discussed the interplay of individual characteristics, including knowledge and culture, interpersonal relationships such as family structure and gender roles, community and organizational factors such as unequal access to health care and access to treatment, and national-level factors including policy and government structure. The ideas and solutions presented here are from a geographically and professionally diverse group of individuals. The collective discussion highlighted the pervasiveness of health disparities across all areas represented by course participants and suggested that disparities are the largest impediment to achieving cancer prevention goals.
    Journal of Oncology Practice 10/2013;
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    ABSTRACT: Background. Carcinogenic human papillomaviruses (HPV) cause a large proportion of anal cancers. HIV-infected men who have sex with men (MSM) are at increased risk of HPV infection and anal cancer compared to HIV-negative men. We evaluated risk factors for HPV infection and anal precancer in a population of HIV-infected MSM.Methods. Our study included 305 MSM at an HIV/AIDS clinic in the Kaiser Permanente Northern California Health Maintenance Organization. Logistic regression was used to estimate associations of risk factors comparing (1) men without anal HPV infection, (2) men with anal HPV infection, but no precancer, and (3) men with anal precancer.Results. Low CD4 count (<350 cells/mm(3)) and previous Chlamydia infection were associated with an increased risk of carcinogenic HPV infection (OR 3.65 95%CI 1.28-10.40, OR 4.24 95%CI 1.16-15.51, respectively). History of smoking (OR 2.71 95%CI 1.43-5.14), duration, recency, and dose of smoking, increased the risk of anal precancer among carcinogenic HPV-positive men, but had no association with HPV infection.Conclusions. We found distinct risk factors for anal HPV infection and anal precancer. Risk factors for HPV infection and anal precancer are similar to established risk factors for cervical cancer progression.
    The Journal of Infectious Diseases 08/2013; · 5.85 Impact Factor
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    ABSTRACT: OBJECTIVE: Chromosomal gains at 3q26, 5p15 and 20q13 have been described in cervical precancer and cancer. We evaluated a novel fluorescence in situ hybridization (FISH) assay that detects gains at these three loci simultaneously as a possible biomarker for detecting cervical precancer. METHODS: Chromosomal copy numbers at 3q26 (3q), 5p15 (5p), 20q13 (20q) and the centromere of chromosome7 (cen7) in liquid-based cytology specimens from 168 women enrolled in the Biopsy Study were determined by FISH. The number of cells with ≥3 or ≥4 signals for a genomic locus was enumerated and diagnostic test performance measures were calculated using receiver operating characteristic (ROC) analyses. Sensitivity and specificity values were determined for the detection of CIN2+ and/or HSIL. RESULTS: The median number of cells with ≥3 signals increased with the severity of cervical lesion for each genomic locus (p-trend<0.02 for each locus). ROC analysis for the number of cells with ≥3 signals resulted in area under the curve values of 0.70 (95% CI: 0.54-0.86), 0.67 (0.52-0.83), 0.67 (0.51-0.83) and 0.78 (0.64-0.92) for 3q, 5p, 20q and cen7, respectively, for the detection of CIN2+ and/or HSIL. Positivity for gains at multiple loci resulted in only slightly better test performance measures than those for the individual probes for four distinct combinations of probes. CONCLUSIONS: Chromosomal gains at 3q, 5p, 20q and cen7 are associated with severity of cervical lesions. Further studies are required to quantify risk stratification of FISH assays for cervical cancer screening.
    Gynecologic Oncology 06/2013; · 3.93 Impact Factor
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    Patricia Luhn, Nicolas Wentzensen
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    ABSTRACT: Current cervical cancer screening programs are changing due to the development of tests that detect the presence of human papillomavirus (HPV), the cause of cervical cancer. These tests are more sensitive than cytology-based methods for detecting cervical precancer and a negative test offers long-term assurance that cervical cancer will not develop and therefore longer screening intervals can be achieved. In screening programs, HPV-based tests have been approved to triage women with equivocal cytology results and as a primary testing method in conjunction with cytology. HPV-based tests also have a role in determining risk of recurrence after treatment for cervical precancer as well as in surveillance for vaccine-related changes in HPV genotype prevalence.
    Current obstetrics and gynecology reports. 06/2013; 2(2):76-85.
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    ABSTRACT: BACKGROUND: Circulating adipokine levels may be associated with endometrial cancer risk, yet few studies have evaluated these markers prospectively. METHODS: We conducted a nested case-control study of postmenopausal women in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (n=78,216), including 167 incident endometrial cancer cases and 327 controls that were matched on age, study center, race, study year of diagnosis, year of blood draw, time of day of blood draw and menopausal hormone therapy (MHT) use. Adipokine and estradiol levels were categorized into tertiles (T). Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of adiponectin, leptin and visfatin with endometrial cancer risk were estimated by conditional logistic regression, adjusting for known endometrial cancer risk factors, including body mass index (BMI) and circulating estradiol levels. RESULTS: Adiponectin levels were inversely associated with risk of endometrial cancer [OR T3vsT1=0.48 (95%CI: 0.29-0.80); p-trend<0.01], whereas elevated leptin levels showed a positive association [2.77 (1.60-4.79); p-trend<0.01]. These results remained significant after adjustment for estradiol, but not after further adjustment for BMI. When analyses were restricted to non-MHT users, associations of adiponectin and leptin were stronger and remained significant after adjustment for estradiol and BMI [0.27 (0.09-0.80); p-trend=0.01 and 4.29 (1.07-17.15); p-trend=0.02, respectively]. Non-significant positive associations were observed for visfatin. CONCLUSION: Adipokines may influence endometrial cancer risk through pathways other than estrogen-mediated cell growth in postmenopausal women not currently on MHT. Impact: Understanding how adipokines influence endometrial cancer risk may help to elucidate biological mechanisms important for the observed obesity-endometrial cancer association.
    Cancer Epidemiology Biomarkers &amp Prevention 05/2013; · 4.56 Impact Factor
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    ABSTRACT: OBJECTIVE: Co-factors for cervical cancer, including oral contraceptive (OC) use, smoking and multiparity have been identified; however, the stage at which they act in cervical carcinogenesis is not clear. We compared established risk factors among women with CIN2 and CIN3 to evaluate the heterogeneity of these factors in precancer and also assessed their role during cervical carcinogenesis. METHODS: The current analysis included 2783 women with various stages of cervical disease who were enrolled in the Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED) and the Biopsy Study. Associations of co-factors within cervical precancer and at different stages of cervical carcinogenesis were estimated using logistic regression. RESULTS: Long-term OC use (10+ years vs. never: OR=2.42, 95% CI: [1.13-5.15]), multiparity (3+ births vs. nulliparous: OR=1.54 [1.04-2.28]), smoking (ever vs. never: OR=1.95 [1.48-2.58]), and no Pap test in the previous five years (2.05 [1.32-3.17]) were positively associated with CIN3 compared to CIN2. We observed that long-term OC use, parity and smoking were associated with an increased risk of CIN3 compared to <CIN2 (1.97 [1.12-3.46]; 2.233 [1.59-3.11]; 2.60 [2.04-3.30], respectively), whereas associations were not significantly different (OC use, parity) or showed decreased risk (smoking) comparing cancer to CIN3. CONCLUSIONS: Differences in established risk factors suggest that CIN3 is a more specific definition of precancer than CIN2. Hormonally-related factors and smoking play a role in the transition from human papillomavirus infection to precancer.
    Gynecologic Oncology 11/2012; · 3.93 Impact Factor
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    ABSTRACT: The Principles and Practice of Cancer Prevention and Control course (Principles course) is offered annually by the National Cancer Institute Cancer Prevention Fellowship Program. This 4-week postgraduate course covers the spectrum of cancer prevention and control research (e.g., epidemiology, laboratory, clinical, social, and behavioral sciences) and is open to attendees from medical, academic, government, and related institutions across the world. In this report, we describe a new addition to the Principles course syllabus, which was exclusively a lecture-based format for over 20 years. In 2011, cancer prevention fellows and staff designed and implemented small group discussion sessions as part of the curriculum. The goals of these sessions were to foster an interactive environment, discuss concepts presented during the Principles course, exchange ideas, and enhance networking among the course participants and provide a teaching and leadership opportunity to current cancer prevention fellows. Overall, both the participants and facilitators who returned the evaluation forms (n = 61/87 and 8/10, respectively) reported a high satisfaction with the experience for providing both an opportunity to explore course concepts in a greater detail and to network with colleagues. Participants (93 %) and facilitators (100 %) stated that they would like to see this component remain a part of the Principles course curriculum, and both groups provided recommendations for the 2012 program. The design, implementation, and evaluation of this initial discussion group component of the Principles course are described herein. The findings in this report will not only inform future discussion group sessions in the Principles course but may also be useful to others planning to incorporate group learning into large primarily lecture-based courses.
    Journal of Cancer Education 06/2012; 27(3):428-35. · 0.88 Impact Factor
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    ABSTRACT: While organized screening programs in industrialized countries have significantly reduced cervical cancer incidence, cytology-based screening has several limitations. Equivocal or mildly abnormal Pap tests require costly retesting or diagnostic work-up by colposcopy and biopsy. In low-resource countries, it has been difficult to establish and sustain cytology-based programs. Advances in understanding human papillomavirus biology and the natural history of human papillomavirus-related precancers and cancers have led to the discovery of a range of novel biomarkers in the past decade. In this article, we will discuss the potential role of new biomarkers for primary screening, triage and diagnosis in high-resource countries and their promise for prevention efforts in resource constrained settings.
    Future Microbiology 09/2011; 6(9):1083-98. · 4.02 Impact Factor

Publication Stats

32 Citations
29.36 Total Impact Points

Institutions

  • 2013–2014
    • National Cancer Institute (USA)
      • Division of Cancer Epidemiology and Genetics
      Maryland, United States
  • 2011–2013
    • National Institutes of Health
      • Division of Cancer Epidemiology and Genetics
      Bethesda, MD, United States