Elizabeth Platz

Publications (11)26.54 Total impact

• Article: Designs combining instrumental variables with case-control: estimating principal strata causal effects.

  Russell T Shinohara, Constantine E Frangakis, Elizabeth Platz, Konstantinos Tsilidis
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  ABSTRACT: The instrumental variables framework is commonly used for the estimation of causal effects from cohort samples. However, the combination of instrumental variables with more efficient designs such as case-control sampling requires new methodological consideration. For example, as the use of Mendelian randomization studies is increasing and the cost of genotyping and gene expression data can be high, the analysis of data gathered from more cost-effective sampling designs is of prime interest. We show that the standard instrumental variables analysis does not appropriately estimate the causal effects of interest when the instrumental variables design is combined with the case-control design. We also propose a method that can estimate the causal effects in such combined designs. We illustrate the method with a study in oncology.
  The International Journal of Biostatistics 01/2012; 8(1). · 1.28 Impact Factor
• Article: Shift from pStat6 to pStat3 predominance is associated with inflammatory bowel disease-associated dysplasia.

  Elizabeth C Wick, Robert E LeBlanc, Guillermo Ortega, Chelsea Robinson, Elizabeth Platz, Drew M Pardoll, Chris Iacobuzio-Donahue, Cynthia L Sears
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  ABSTRACT: Activated Stat3 is an important mediator of oncogenesis in the colon. To test the hypothesis that select Stat activation and/or the pattern of Stat activation serves as a marker for early neoplastic transformation, we examined the distribution of activated Stat1(pStat1), Stat6(pStat6), and Stat3(pStat3) in colitis along the continuum of inactive disease to colitis-associated cancer. Tissue microarrays were constructed using colonoscopy biopsy and surgical specimens from 67 patients with ulcerative colitis or Crohn's colitis and 11 controls. In all, 111 sets of samples were analyzed representing normal tissue, active disease, low-grade dysplasia, high-grade dysplasia, and colitis-associated cancer. Immunohistochemistry to detect pStat1, pStat6, and pStat3 in colonic epithelial and mucosal immune cells was then correlated with clinical and pathological data (tumor location, histologic type, grade, and lymph node involvement). In 50% of colitis-associated cancer samples, pStat3 was detected prominently in epithelial cells, where it was routinely associated with intense pStat3 staining in surrounding immune cells. Stat3 activation was greater in low-grade tumors than in high-grade ones (P < 0.05). pStat6 expression was more common in normal tissues than in colitis-associated cancer (P < 0.05). pStat1 was detected in a small subset of immune cells in patients with chronic inactive and active colitis, low- and high-grade dysplasia, but not in colitis-associated cancer. pStat3 may be a marker for neoplastic transformation in patients with colitis. A shift from predominant immune cell Stat6 activation to Stat3 activation accompanies the onset of dysplasia with concomitant increased epithelial cell Stat3 activation in a subset of patients.
  Inflammatory Bowel Diseases 10/2011; 18(7):1267-74. · 4.86 Impact Factor
• Article: Association between plasma total cholesterol concentration and incident prostate cancer in the CLUE II cohort.

  Alison M Mondul, Sandra L Clipp, Kathy J Helzlsouer, Elizabeth A Platz
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  ABSTRACT: Statin drugs appear to protect against advanced and possibly high-grade prostate cancer, perhaps through cholesterol-lowering. Thus, we evaluated the association between plasma cholesterol and prostate cancer. We conducted a prospective study in the CLUE II cohort of Washington County, MD. Included were 6,816 male county residents aged 35+ years old who did not have a cancer diagnosis at baseline in 1989. Plasma cholesterol, measured enzymatically at baseline, was categorized by clinical cutpoints. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for total (n = 438) and high-grade (Gleason sum > or =7, n = 137) prostate cancer. Compared to men with high cholesterol (> or =240 mg/dl), men with desirable (<200 mg/dl) or borderline (200 to <240 mg/dl) levels were less likely to develop high-grade prostate cancer, particularly when restricting to organ-confined cases (HR: 0.68, 95% CI 0.40-1.18; P trend = 0.12) and among men with higher BMI (HR: 0.36, 95% CI 0.16-0.79; P trend = 0.02). Results were unchanged after excluding cholesterol-lowering drug users. Cholesterol was not associated with total prostate cancer. Our study supports two prior ones suggesting that cholesterol influences risk of high-grade prostate cancer, and indirectly supports the hypothesis that cholesterol-lowering is a mechanism by which statins are protective.
  Cancer Causes and Control 10/2009; 21(1):61-8. · 2.88 Impact Factor
• Article: Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer.

  Konstantinos K Tsilidis, Kathy J Helzlsouer, Michael W Smith, Victoriya Grinberg, Judith Hoffman-Bolton, Sandra L Clipp, Kala Visvanathan, Elizabeth A Platz
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  ABSTRACT: The association of 17 candidate single nucleotide polymorphisms (SNPs) in IL10 and other immune response genes (CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and genes related to obesity (PPARG, TCF7L2, ADIPOQ, LEP) with colorectal cancer was investigated. Haplotype tagging SNPs were chosen for IL10, CRP, and TLR4. Incident colorectal cancer cases (n = 208) and matched controls (n = 381) were identified between baseline in 1989 and 2003 among participants in the CLUE II cohort. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression. Compared with the AA genotype at the candidate IL10-1082 locus (rs1800896), carrying one (OR, 0.79; 95% CI, 0.53-1.18) or two (OR, 0.58; 95% CI, 0.35-0.95) G alleles, a known higher producer of the anti-inflammatory cytokine IL-10, was associated with lower risk of colorectal cancer (p trend = 0.03). Statistically significant associations with colorectal cancer were observed for three tagSNPs in IL10 (rs1800890, rs3024496, rs3024498) and one common haplotype, but these associations were due to high linkage disequilibrium with IL10-1082. Two CRP haplotypes (global p = 0.04) and TLR4 tagSNPs (rs7873784, rs11536891), but not TLR4 haplotypes, were associated with colorectal cancer. Our study suggests that polymorphisms in IL10, and also possibly in CRP and other genes related to immune response or obesity may be associated with colorectal cancer.
  Cancer Causes and Control 09/2009; 20(9):1739-51. · 2.88 Impact Factor
• Article: Correlates of sexually transmitted infection histories in a cohort of American male health professionals.

  Siobhan Sutcliffe, Ichiro Kawachi, John F Alderete, Charlotte A Gaydos, Lisa P Jacobson, Frank J Jenkins, Raphael P Viscidi, Jonathan M Zenilman, Elizabeth A Platz
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  ABSTRACT: Several epidemiologic studies have investigated sexually transmitted infections (STIs) and later risk of genitourinary conditions with suggestive positive results. While these results may reflect causal associations, other possible explanations include confounding by factors possibly related to both STI acquisition and genitourinary condition risk such as recognized STI-risk factors/correlates, and other factors not typically considered in relation to STIs (e.g., general health-related behaviors or markers of such behaviors). Very few of these factors have been investigated in older populations in which STIs and genitourinary conditions are typically studied. Therefore, we investigated STI history correlates in one such population, the Health Professionals Follow-up Study. We ascertained histories of potential correlates, gonorrhea, syphilis by questionnaire (n = 36,032), and performed serologic testing for Chlamydia trachomatis, Trichomonas vaginalis, human papillomavirus, and human herpesvirus type 8 infection in a subset (n = 651). Positive correlations were observed for African-American race, foreign birth, southern residence, smoking, alcohol consumption, ejaculation frequency, vasectomy, and high cholesterol. Inverse correlations were observed for social integration and routine health-related examinations. These findings provide useful information on potential confounders for epidemiologic investigations of STIs and chronic diseases, and interesting new hypotheses for STI prevention (e.g., STI counseling before vasectomy).
  Cancer Causes and Control 09/2009; 20(9):1623-34. · 2.88 Impact Factor
• Article: Metabolic syndrome components and colorectal adenoma in the CLUE II cohort.

  Konstantinos K Tsilidis, Frederick L Brancati, Michael N Pollak, Nader Rifai, Sandra L Clipp, Judith Hoffman-Bolton, Kathy J Helzlsouer, Elizabeth A Platz
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  ABSTRACT: Metabolic syndrome components have been associated with colorectal cancer in several studies; however, evidence for colorectal adenomas is limited. Thus, we evaluated the association between markers of the metabolic syndrome with colorectal adenoma development in a nested case-control study. Colorectal adenoma cases (n = 132) and matched controls, who had a negative sigmoidoscopy or a colonoscopy (n = 260), were identified between baseline in 1989 and 2000 among participants in the CLUE II cohort of Washington County, Maryland. Concentrations of C-peptide, insulin-like growth factor binding protein-1, glycosylated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured in baseline blood specimens. Body mass index was calculated using baseline height and weight. Use of medications to treat diabetes mellitus was self-reported at baseline. Blood pressure was measured at baseline. Distributional cutpoints of the latter markers were used to define the metabolic syndrome components (hyperinsulinemia, hyperglycemia, obesity, dyslipidemia, and hypertension) present at baseline. No statistically significant associations with adenomas were observed for the markers of the metabolic syndrome, with the exception of a strong positive association for use of diabetes medications (OR, 8.00; 95% CI, 1.70-37.67), albeit based on small numbers. Our findings do not support that components of the metabolic syndrome influence risk of colorectal adenomas, except possibly for severe diabetes mellitus warranting medical treatment.
  Cancer Causes and Control 09/2009; 21(1):1-10. · 2.88 Impact Factor
• Article: Association of cigarette smoking, alcohol consumption, and physical activity with sex steroid hormone levels in US men.

  Meredith S Shiels, Sabine Rohrmann, Andy Menke, Elizabeth Selvin, Carlos J Crespo, Nader Rifai, Adrian Dobs, Manning Feinleib, Eliseo Guallar, Elizabeth A Platz
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  ABSTRACT: We evaluated the associations of smoking, alcohol consumption, and physical activity with sex steroid hormone concentrations among 1,275 men > or =20 years old who participated in the Third National Health and Nutrition Examination Survey (NHANES III). Serum concentrations of testosterone, estradiol, and sex hormone-binding globulin (SHBG) were measured. We compared geometric mean concentrations across levels of smoking, alcohol, and physical activity using multiple linear regression. Current smokers had higher total testosterone (5.42, 5.10, and 5.26 ng/ml in current, former, and never smokers), free testosterone (0.110, 0.102, and 0.104 ng/ml), total estradiol (40.0, 34.5, and 33.5 pg/ml), and free estradiol (1.05, 0.88, and 0.84 pg/ml) compared with former and never smokers (all p < or = 0.05). Men who consumed > or =1 drink/day had lower SHBG than men who drank less frequently (31.5 vs. 34.8 nmol/l, p = 0.01); total (p-trend = 0.08) and free testosterone (p-trend = 0.06) increased with number of drinks per day. Physical activity was positively associated with total (p-trend = 0.01) and free testosterone (p-trend = 0.05). In this nationally representative sample of men, smoking, alcohol, and physical activity were associated with hormones and SHBG, thus these factors should be considered as possible confounders or upstream variables in studies of hormones and men's health, including prostate cancer.
  Cancer Causes and Control 03/2009; 20(6):877-86. · 2.88 Impact Factor
• Article: Temporal stability and age-related prevalence of loss of imprinting of the insulin-like growth factor-2 gene.

  Marcia Cruz-Correa, Ronghua Zhao, Myriam Oviedo, Raul D Bernabe, Mercedes Lacourt, Alberto Cardona, Reynold Lopez-Enriquez, Steven Wexner, Carmen Cuffari, Linda Hylind, Elizabeth Platz, Hengmi Cui, Andrew P Feinberg, Francis M Giardiello
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  ABSTRACT: Loss of genomic imprinting (LOI) of the insulin-like growth factor-2 gene (IGF2) is an epigenetic change involving abnormal activation of the normally silent maternally inherited allele. LOI of IGF2 gene is found in tumor tissue, normal adjoining mucosa and peripheral blood lymphocytes (PBL) of some patients with colorectal cancer (CRC), suggesting that this alteration precedes and is a risk factor for CRC. However, whether LOI of IGF2 is transitory or remains a permanent epigenetic alteration is unknown. Four-hundred patients, mean age 60.7 years (range 15-95), 287 (80%) Caucasian were studied. This included 210 (51.4%) patients with no colorectal neoplasia, and 190 (48.6) with colorectal neoplasia. LOI of IGF2 was present in all age strata examined, and no statistically significant association across age strata (p trend > 0.05) was noted. Forty-nine patients had repeat analysis of blood imprinting status at a mean follow up time of 38.2 +/- 12.9 months. All but three patients had the same imprinting status at follow up (94% agreement, kappa 0.79, p < 0.001). Genomic imprinting was stable for patients with and without colorectal neoplasia. Standard RT-PCR assays for imprinting analysis of IGF2 were performed on PBL from ApaI informative individuals recruited at baseline and repeated 1 to 3 years later. Prevalence of LOI of IGF2 was also evaluated according to age strata. LOI of the IGF2 gene in PBL appears to be a stable epigenetic phenomenon in most patients. Furthermore, LOI of IGF2 was not associated with age, suggesting an inherited or congenital epigenetic event. These findings support the concept that LOI of IGF2 may be a useful risk factor for CRC predisposition.
  Epigenetics: official journal of the DNA Methylation Society 03/2009; 4(2):114-8. · 4.58 Impact Factor
• Source

  Available from: epi-ucsf.org

  Article: Risk factors for hearing loss in US adults: data from the National Health and Nutrition Examination Survey, 1999 to 2002.

  Yuri Agrawal, Elizabeth A Platz, John K Niparko
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  ABSTRACT: To evaluate and compare the effects of cardiovascular risk factors (hypertension, smoking, diabetes) and noise exposure (occupational, recreational, firearm) on frequency-specific audiometric thresholds among US adults while assessing synergistic interactions between these exposures. National cross-sectional survey. United States adults aged 20 to 69 years who participated in the 1999 to 2002 National Health and Nutrition Examination Survey (N = 3,527). Air-conduction thresholds at 0.5 to 8 kHz (dB) in the poorer-hearing ear. Multivariate models adjusted for age, sex, race/ethnicity, and educational level. : Exposure to firearm noise was significantly associated with high-frequency (4-8 kHz) hearing loss (HL), whereas smoking and diabetes were associated with significantly increased hearing thresholds across the frequency range (0.5-8 kHz). A significant interaction was observed between exposure to firearm noise and heavy smoking such that firearm noise was associated with a mean 8-dB hearing loss in heavy smokers compared with a mean 2-dB hearing loss in nonsmokers at 8 kHz. We also observed significant interactions between firearm noise exposure and diabetes. Noise exposure was associated with high-frequency HL, whereas cardiovascular risk generated by smoking and diabetes was associated with both high- and low-frequency HL. The frequency-specific effects of these exposures may offer insight into mechanisms of cochlear damage. We demonstrated an interaction between cardiovascular risk and noise exposures, possibly as a result of cochlear vulnerability due to microvascular insufficiency. Such significant interactions provide proof of principle that certain preexisting medical conditions can potentiate the effect of noise exposure on hearing. Data-based stratification of risk should guide our counseling of patients regarding HL.
  Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 01/2009; 30(2):139-45. · 1.44 Impact Factor
• Article: The association of urinary cadmium with sex steroid hormone concentrations in a general population sample of US adult men

  Andy Menke, Eliseo Guallar, Meredith Shiels, Sabine Rohrmann, Shehzad Basaria, Nader Rifai, William Nelson, Elizabeth Platz
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  ABSTRACT: Abstract Background Studies investigating the association of cadmium and sex steroid hormones in men have been inconsistent, but previous studies were relatively small. Methods In a nationally representative sample of 1,262 men participating in the morning examination session of phase I (1998–1991) of the third National Health and Nutrition Examination Survey, creatinine corrected urinary cadmium and serum concentrations of sex steroid hormones were measured following a standardized protocol. Results After adjustment for age and race-ethnicity, higher cadmium levels were associated with higher levels of total testosterone, total estradiol, sex hormone-binding globulin, estimated free testosterone, and estimated free estradiol (each p-trend < 0.05). After additionally adjusting for smoking status and serum cotinine, none of the hormones maintained an association with urinary cadmium (each p-trend > 0.05). Conclusion Urinary cadmium levels were not associated with sex steroid hormone concentrations in a large nationally representative sample of US men.
  BMC Public Health. 01/2008;
• Article: Prostate-specific antigen, sexual behavior, and sexually transmitted infections in US men 40–59 years old, 2001–2004: a cross – sectional study

  David Werny, Mona Saraiya, Xiao Chen, Elizabeth Platz
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  ABSTRACT: Abstract Background Sexually transmitted infections (STIs) are hypothesized to play a role in the development of prostate cancer, perhaps due to inflammation-induced oncogenesis. We assessed in a nationally representative population of middle-aged men whether sexual behavior indicators for an increased risk of genital infection were associated with serum prostate-specific antigen (PSA) concentration, a marker of prostatic disease and inflammation. Results The percentage of men between the ages of 40 and 59 with a PSA ≥ 4.0 ng/ml was 2.6% (95% confidence interval [CI], 1.8% – 3.8%). The percentage of men between the ages of 40 and 59 self-reporting a past diagnosis of genital warts or genital herpes, or a recent diagnosis of gonorrhea or chlamydia is estimated to be 7.3% (95% CI, 6.2% – 8.6%). Men self-reporting that they had had sex without using a condom in the past month had a lower PSA concentration and higher %fPSA than those who did not. There were no associations between any of the other sexual activity or laboratory measures and PSA or %fPSA. Conclusion In this nationally representative sample of middle-aged American men, we did not find consistent evidence for an association between sexual behavior or a history of STIs and PSA levels. Therefore, sexual factors are unlikely to lead to falsely elevated PSA tests in this population. We cannot rule out the role of these factors in causing false positive PSA tests in subgroups of the population that have a higher prevalence of high-risk sexual behavior, and more protracted or recent exposures to these agents.
  Infectious Agents and Cancer. 01/2007;