Anika Hüsing

Publications (24) View all

• Article: Prediction of breast cancer risk by genetic risk factors, overall and by hormone receptor status.

  Anika Hüsing, Federico Canzian, Lars Beckmann, Montserrat Garcia-Closas, W Ryan Diver, Michael J Thun, Christine D Berg, Robert N Hoover, Regina G Ziegler, Jonine D Figueroa, [......], Shumin Zhang, Sara Lindström, Susan E Hankinson, Elio Riboli, David J Hunter, Brian E Henderson, Stephen J Chanock, Christopher A Haiman, Peter Kraft, Rudolf Kaaks
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  ABSTRACT: OBJECTIVE: There is increasing interest in adding common genetic variants identified through genome wide association studies (GWAS) to breast cancer risk prediction models. First results from such models showed modest benefits in terms of risk discrimination. Heterogeneity of breast cancer as defined by hormone-receptor status has not been considered in this context. In this study we investigated the predictive capacity of 32 GWAS-detected common variants for breast cancer risk, alone and in combination with classical risk factors, and for tumours with different hormone receptor status. MATERIAL AND METHODS: Within the Breast and Prostate Cancer Cohort Consortium, we analysed 6009 invasive breast cancer cases and 7827 matched controls of European ancestry, with data on classical breast cancer risk factors and 32 common gene variants identified through GWAS. Discriminatory ability with respect to breast cancer of specific hormone receptor-status was assessed with the age adjusted and cohort-adjusted concordance statistic (AUROC(a)). Absolute risk scores were calculated with external reference data. Integrated discrimination improvement was used to measure improvements in risk prediction. RESULTS: We found a small but steady increase in discriminatory ability with increasing numbers of genetic variants included in the model (difference in AUROC(a) going from 2.7% to 4%). Discriminatory ability for all models varied strongly by hormone receptor status. DISCUSSION AND CONCLUSIONS: Adding information on common polymorphisms provides small but statistically significant improvements in the quality of breast cancer risk prediction models. We consistently observed better performance for receptor-positive cases, but the gain in discriminatory quality is not sufficient for clinical application.
  Journal of Medical Genetics 09/2012; 49(9):601-608. · 6.36 Impact Factor
• Article: Serum enterolactone and prognosis of postmenopausal breast cancer.

  Katharina Buck, Alina Vrieling, Aida Karina Zaineddin, Susen Becker, Anika Hüsing, Rudolf Kaaks, Jakob Linseisen, Dieter Flesch-Janys, Jenny Chang-Claude
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  ABSTRACT: Lignans--plant-derived compounds with estrogen-dependent and -independent anticarcinogenic properties--have been associated with postmenopausal breast cancer risk, but data are limited regarding their effect on survival. Dietary lignans are metabolized to enterolignans, which are subsequently absorbed and become bioavailable. We assessed the prognosis of 1,140 postmenopausal patients with breast cancer age 50 to 74 years who were diagnosed between 2002 and 2005. Vital status through the end of 2009 was ascertained via local population registries, and deaths were verified by death certificates. Information on recurrences and secondary tumors was verified by clinical records and attending physicians. Associations of postdiagnostic serum enterolactone (a biomarker for dietary lignans) with overall survival and distant disease-free survival were assessed by using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic factors. Median enterolactone levels for deceased patients and those still alive were 17.0 and 21.4 nmol/L, respectively. During a median of 6.1 years of follow-up after diagnosis, 162 deaths were confirmed. Higher serum enterolactone levels were associated with significantly reduced hazard ratios (HRs) for death (HR per 10 nmol/L increment, 0.94; P = .04; HR for the highest quartile, 0.58; 95% CI, 0.34 to 0.99). For distant disease, HR was 0.94 per 10 nmol/L increment (P = .08) and 0.62 (95% CI, 0.35 to 1.09) for the highest quartile. The highest quartile of serum enterolactone was associated with a significantly reduced risk of death only for estrogen receptor-negative tumors (HR, 0.27; 95% CI, 0.08 to 0.87) but not for estrogen receptor-positive tumors (HR, 0.91; 95% CI, 0.45 to 1.84: P for heterogeneity = .09). Postmenopausal patients with breast cancer who have high serum enterolactone levels may have better survival.
  Journal of Clinical Oncology 09/2011; 29(28):3730-8. · 18.37 Impact Factor
• Article: Genetic variability of the forkhead box O3 and prostate cancer risk in the European Prospective Investigation on Cancer.

  Daniele Campa, Anika Hüsing, Lucie Dostal, Angelika Stein, Dagmar Drogan, Heiner Boeing, Anne Tjønneland, Nina Roswall, Jane Nautrup Østergaard, Kim Overvad, [......], Rosario Tumino, Paolo Vineis, H Bas Bueno-de-Mesquita, Per Lenner, Mattias Johansson, Mazda Jenab, David Cox, Afshan Siddiq, Rudolf Kaaks, Federico Canzian
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  ABSTRACT: Forkhead box O3 (FOXO3) has a wide range of functions: it promotes tumor suppression, cell cycle arrest, repair of damaged DNA, detoxification of reactive oxygen species, apoptosis and plays a pivotal role in promoting longevity. FOXO3 is a key downstream target of the PI3K-Akt pathway in response to cellular stimulation by growth factors or insulin and has been proposed as a bridge between ageing and tumor suppression. Three SNPs in the FOXO3 gene (rs3800231, rs9400239 and rs479744) that have been shown to be strongly and consistently associated with longevity, were examined in relation to PC risk in a case control study of 1571 incident PC cases and 1840 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). There was no statistically significant association between the SNPs and PC risk regardless of the model of inheritance (dominant, codominant and recessive). The associations were not modified by disease aggressiveness, circulating levels of steroid sex hormones, or IGFs or BMI. We conclude that polymorphisms in the FOXO3 gene that are associated with longevity are not major risk factors for PC risk, in this population of Caucasian men.
  Oncology Reports 06/2011; 26(4):979-86. · 1.84 Impact Factor
• Source

  Available from: Federico Canzian

  Article: Genetic variability of the mTOR pathway and prostate cancer risk in the European Prospective Investigation on Cancer (EPIC).

  Daniele Campa, Anika Hüsing, Angelika Stein, Lucie Dostal, Heiner Boeing, Tobias Pischon, Anne Tjønneland, Nina Roswall, Kim Overvad, Jane Nautrup Østergaard, [......], H Bas Bueno-de-Mesquita, Göran Hallmans, Mattias Johansson, Isabelle Romieu, Mazda Jenab, David G Cox, Afshan Siddiq, Elio Riboli, Federico Canzian, Rudolf Kaaks
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  ABSTRACT: The mTOR (mammalian target of rapamycin) signal transduction pathway integrates various signals, regulating ribosome biogenesis and protein synthesis as a function of available energy and amino acids, and assuring an appropriate coupling of cellular proliferation with increases in cell size. In addition, recent evidence has pointed to an interplay between the mTOR and p53 pathways. We investigated the genetic variability of 67 key genes in the mTOR pathway and in genes of the p53 pathway which interact with mTOR. We tested the association of 1,084 tagging SNPs with prostate cancer risk in a study of 815 prostate cancer cases and 1,266 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). We chose the SNPs (n = 11) with the strongest association with risk (p<0.01) and sought to replicate their association in an additional series of 838 prostate cancer cases and 943 controls from EPIC. In the joint analysis of first and second phase two SNPs of the PRKCI gene showed an association with risk of prostate cancer (OR(allele) = 0.85, 95% CI 0.78-0.94, p = 1.3 x 10⁻³ for rs546950 and OR(allele) = 0.84, 95% CI 0.76-0.93, p = 5.6 x 10⁻⁴ for rs4955720). We confirmed this in a meta-analysis using as replication set the data from the second phase of our study jointly with the first phase of the Cancer Genetic Markers of Susceptibility (CGEMS) project. In conclusion, we found an association with prostate cancer risk for two SNPs belonging to PRKCI, a gene which is frequently overexpressed in various neoplasms, including prostate cancer.
  PLoS ONE 01/2011; 6(2):e16914. · 4.09 Impact Factor
• Article: Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI breast and prostate cancer cohort consortium.

  Federico Canzian, David G Cox, V Wendy Setiawan, Daniel O Stram, Regina G Ziegler, Laure Dossus, Lars Beckmann, Hélène Blanché, Aurelio Barricarte, Christine D Berg, [......], Anne Tjønneland, Dimitrios Trichopoulos, Rosario Tumino, Meredith Yeager, Robert N Hoover, Elio Riboli, Gilles Thomas, Brian E Henderson, Rudolf Kaaks, Heather Spencer Feigelson
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  ABSTRACT: There is extensive evidence that increases in blood and tissue concentrations of steroid hormones and of insulin-like growth factor I (IGF-I) are associated with breast cancer risk. However, studies of common variation in genes involved in steroid hormone and IGF-I metabolism have yet to provide convincing evidence that such variants predict breast cancer risk. The Breast and Prostate Cancer Cohort Consortium (BPC3) is a collaboration of large US and European cohorts. We genotyped 1416 tagging single nucleotide polymorphisms (SNPs) in 37 steroid hormone metabolism genes and 24 IGF-I pathway genes in 6292 cases of breast cancer and 8135 controls, mostly Caucasian, postmenopausal women from the BPC3. We also imputed 3921 additional SNPs in the regions of interest. None of the SNPs tested was significantly associated with breast cancer risk, after correction for multiple comparisons. The results remained null when cases and controls were stratified by age at diagnosis/recruitment, advanced or nonadvanced disease, body mass index, with or without in situ cases; or restricted to Caucasians. Among 770 estrogen receptor-negative cases, an SNP located 3' of growth hormone receptor (GHR) was marginally associated with increased risk after correction for multiple testing (P(trend) = 1.5 × 10(-4)). We found no significant overall associations between breast cancer and common germline variation in 61 genes involved in steroid hormone and IGF-I metabolism in this large, comprehensive study. Although previous studies have shown that variations in these genes can influence endogenous hormone levels, the magnitude of the effect of single SNPs does not appear to be sufficient to alter breast cancer risk.
  Human Molecular Genetics 10/2010; 19(19):3873-84. · 7.64 Impact Factor