Low risk of solid tumors in persons with Down syndrome

Purpose:The aim of this study was to investigate cancer incidence in a large cohort of persons with Down syndrome.Methods:Down syndrome was identified from the Danish Cytogenetic Register. Cancer occurrence was identified by linkage to the Danish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated based on observed and expected numbers from rates for all Danish residents. The cohort consisted of 3,530 persons with Down syndrome contributing 89,570 person-years at risk.Results:Acute leukemia risk was highest from 1–4 years of age and remained elevated until age 30. The overall risk of solid tumors was decreased (SIR 0.45; 95% CI 0.34–0.59), especially in persons 50 years or older (SIR 0.27; 95% CI 0.16–0.43). We found a significantly lower risk of lung cancer (SIR 0.10; 95% CI 0.00–0.56), breast cancer (SIR 0.16; 95% CI 0.03–0.47), and cervical cancer (SIR 0.0; 95% CI 0.00–0.77). Testicular cancer was the only solid tumor with an increased SIR (2.9; 95% CI 1.6–4.8).Conclusions:The risk of all major groups of solid tumors was decreased, except testicular cancer. Altered screening strategies should be considered for persons with Down syndrome. This unusual pattern of cancer occurrence may help understanding carcinogenesis in the general population.Genet Med 18 11, 1151–1157.

[1]  S. Culine,et al.  A Lower Risk of Dying from Urological Cancer in Down Syndrome: Clue for Cancer Protecting Genes on Chromosome 21 , 2009, Urologia Internationalis.

[2]  Sven Cnattingius,et al.  Mortality and cancer incidence among individuals with Down syndrome. , 2003, Archives of internal medicine.

[3]  Apoptosis in Down’s syndrome: lessons from studies of human and mouse models , 2013, Apoptosis.

[4]  S. Rasmussen,et al.  Survival among people with Down syndrome: a nationwide population-based study in Denmark , 2012, Genetics in Medicine.

[5]  E. Niebuhr,et al.  Down's syndrome , 1974, Humangenetik.

[6]  N. Ohtake,et al.  Seminoma associated with bilateral cryptorchidism in Down’s syndrome: A case report , 1999, International journal of urology : official journal of the Japanese Urological Association.

[7]  I. Janszky,et al.  Joint effects of nulliparity and other breast cancer risk factors , 2011, British Journal of Cancer.

[8]  S Lovestone,et al.  Brain anatomy and ageing in non-demented adults with Down's syndrome: an in vivo MRI study , 2009, Psychological Medicine.

[9]  J. Merrick,et al.  Cancer incidence in persons with Down syndrome in Israel. , 2002, Down's syndrome, research and practice : the journal of the Sarah Duffen Centre.

[10]  R. Hussain,et al.  The profile and incidence of cancer in Down syndrome. , 2007, Journal of intellectual disability research : JIDR.

[11]  K. Bhaskaran,et al.  Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults , 2014, The Lancet.

[12]  L. Richiardi,et al.  Age at surgery for undescended testis and risk of testicular cancer. , 2007, The New England journal of medicine.

[13]  C. Lundsteen,et al.  Detection of chromosomal aberrations in seminomatous germ cell tumours using comparative genomic hybridization , 1997, Genes, chromosomes & cancer.

[14]  A. Kirsch,et al.  Urological manifestations of Down syndrome. , 2004, The Journal of urology.

[15]  Eero Pukkala,et al.  Cancer incidence of persons with down syndrome in Finland: A population‐based study , 2006, International journal of cancer.

[16]  J. Olsen,et al.  Occurrence of cancer in women with Turner syndrome. , 1996, British Journal of Cancer.

[17]  Michael C. Ostrowski,et al.  Trisomy represses ApcMin-mediated tumours in mouse models of Down’s syndrome , 2008, Nature.

[18]  J. Rimmer,et al.  Obesity and associated factors in adults with intellectual disability. , 2014, Journal of intellectual disability research : JIDR.

[19]  P. Clopton,et al.  Evidence for accelerated skin wrinkling among developmentally delayed individuals with Down's syndrome , 1993, Mechanisms of Ageing and Development.

[20]  Jimin Shin,et al.  A single extra copy of Dscr1 improves survival of mice developing spontaneous lung tumors through suppression of tumor angiogenesis. , 2014, Cancer letters.

[21]  C. Stiller,et al.  A very rare cancer in Down syndrome: medulloblastoma. Epidemiological data from 13 countries , 2013, Journal of Neuro-Oncology.

[22]  J. H. Lee,et al.  Early menopause in women with Down's syndrome. , 1997, Journal of intellectual disability research : JIDR.

[23]  H. Storm,et al.  The Danish Cancer Registry--history, content, quality and use. , 1997, Danish medical bulletin.

[24]  R. Hussain,et al.  Breast cancer and the uptake of mammography screening services by women with intellectual disabilities. , 2003, Preventive medicine.

[25]  A. J. Bell,et al.  Prevalence of overweight and obesity in Down's syndrome and other mentally handicapped adults living in the community. , 2008, Journal of intellectual disability research : JIDR.

[26]  V. Beral,et al.  Mortality and cancer incidence in persons with Down's syndrome, their parents and siblings. , 2001 .

[27]  D. Nižetić,et al.  Tumorigenesis in Down's syndrome: big lessons from a small chromosome , 2012, Nature Reviews Cancer.

[28]  Jacob D. Jaffe,et al.  Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 lysine 27 trimethylation , 2014, Nature Genetics.

[29]  George Q. Daley,et al.  Down syndrome suppression of tumor growth and the role of the calcineurin inhibitor DSCR1 , 2009, Nature.

[30]  H. Hasle,et al.  Risks of leukaemia and solid tumours in individuals with Down's syndrome , 2000, The Lancet.

[31]  M. Passos-Bueno,et al.  High serum endostatin levels in Down syndrome: implications for improved treatment and prevention of solid tumours , 2001, European Journal of Human Genetics.

[32]  H. Hasle.  Pattern of malignant disorders in individuals with Down's syndrome. , 2001, The Lancet. Oncology.

[33]  S. Rasmussen,et al.  Social conditions for people with Down syndrome: A register‐based cohort study in Denmark , 2014, American journal of medical genetics. Part A.

[34]  J. Mulliken,et al.  Risk of Vascular Anomalies With Down Syndrome , 2008, Pediatrics.

[35]  B. Skotko,et al.  Estimates of the live births, natural losses, and elective terminations with Down syndrome in the United States , 2015, American journal of medical genetics. Part A.

[36]  S. Rasmussen,et al.  Mortality associated with Down's syndrome in the USA from 1983 to 1997: a population-based study , 2002, The Lancet.

[37]  S. Izraeli,et al.  DYRK1A in Down syndrome: an oncogene or tumor suppressor? , 2012, The Journal of clinical investigation.

[38]  N. Roizen,et al.  Down's syndrome , 2003, The Lancet.

[39]  P. Vyas,et al.  Down syndrome preleukemia and leukemia. , 2015, Pediatric clinics of North America.