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Sökning: WFRF:(Mucci LA)

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  • Mucci, LA, et al. (författare)
  • Environmental and heritable factors in the etiology of oral diseases--a population-based study of Swedish twins
  • 2005
  • Ingår i: Journal of dental research. - : SAGE Publications. - 0022-0345 .- 1544-0591. ; 84:9, s. 800-805
  • Tidskriftsartikel (refereegranskat)abstract
    • A population-based twin study is a useful design for quantification of the effects of genes and environmental factors in disease etiology. We used data from 10,000 Swedish twin pairs to quantify genetic and environmental contributions to tooth loss and periodontal health. Oral health information was obtained from telephone interviews. Structural equation models measured the relative importance of genetic and environmental factors. Genetic factors contributed to 14% of variation in tooth loss among women, and 39% among men. Non-shared environmental factors accounted for one-quarter of risk; environmental factors shared by twins comprised the remainder. Heritability estimates of periodontal disease were 39% and 33% for women and men, respectively, while non-shared environmental factors accounted for the remaining variation. Heritability for both conditions varied as a function of age and smoking status. Analysis of data from this large, population-based study demonstrates a moderate role of genetic factors in oral diseases, and suggests potential gene-environment interactions.
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  • Mucci, LA, et al. (författare)
  • Precision prevention of TMPRSS2: ERG prostate cancer.
  • 2016
  • Ingår i: JOURNAL OF CLINICAL ONCOLOGY. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 34:2
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • 78 Background: Increased integration of tumor biomarker data into prostate cancer epidemiology studies is needed to identify molecular subtypes that underlie its etiology and progression. We hypothesize that the TMPRSS2:ERG gene fusion is a unique prostate cancer subtype that is etiologically distinct from cancers lacking TMPRSS2:ERG. Methods: We leveraged the Physicians’ Health Study and Health Professionals Follow-up Study cohort data on pre- and post-diagnostic lifestyle factors, inherited genetic variants, circulating biomarkers, and clinical data and follow-up for 30 years. We have a tumor repository of men with prostate cancer and tumor tissue microarrays. Using immunohistochemistry, we characterized TMPRSS2:ERG status for 1,491 incident prostate cancer cases in these cohorts, and also have biomarker data on a range of additional markers from immunohistochemistry and mRNA expression profiling. Results: Fifty percent of prostate cancer cases were ERG-positive. ERG-positive cancers show much higher expression of insulin/IGF signaling, PTEN loss, higher VDR expression, as well as expression of mismatch repair genes. In contrast, ERG-negative prostate cancer is characterized by increased presence of chronic inflammation and atrophy. We found higher pre-diagnostic free testosterone levels, but not other sex hormones, were associated with increased risk of ERG-positive (OR = 1.4, 95% CI = 1.0-1.8) but not ERG-negative disease (OR = 0.9, 95% CI = 0.7-1.2). Of 39 known genetic risk loci, six were significantly associated (p < 0.05) with ERG+ versus ERG- cancer (2 expected by chance). Prostate cancer risk factors such as taller height (an indicator of growth factors in puberty) are uniquely associated with ERG-positive prostate cancer. Moreover, we observe a complex interaction of components of insulin/IGF and ERG-status on prostate cancer mortality. Conclusions: TMPRSS2:ERG is a highly prevalent somatic event in prostate cancer that likely defines a unique molecular subtype of this common disease. Understanding the differences between these two prostate cancer subtypes may enhance opportunities for prevention.
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