Surgery Today

, Volume 49, Issue 1, pp 72–81 | Cite as

Prevalence of and risk factors for thyroid carcinoma in patients with familial adenomatous polyposis: results of a multicenter study in Japan and a systematic review

  • Haruki Sada
  • Takao HinoiEmail author
  • Hideki Ueno
  • Tatsuro Yamaguchi
  • Yasuhiro Inoue
  • Tsuyoshi Konishi
  • Hirotoshi Kobayashi
  • Yukihide Kanemitsu
  • Fumio Ishida
  • Hideyuki Ishida
  • Naohiro Tomita
  • Nagahide Matsubara
  • Kenichi Sugihara
Original Article



To investigate the recent Japanese prevalence of thyroid cancer and its characteristics in familial adenomatous polyposis (FAP) patients, through the development of surveillance programs.


The subjects of this study were 282 (93.1%) FAP patients for whom information on thyroid cancer was available, from among 303 patients registered in “the Retrospective Cohort Study of Familial Adenomatous Polyposis in Japan” database. We evaluated the prevalence and risk factors for thyroid cancer and integrated and/or compared our findings with those of previous reports, using a systematic review, including a meta-analysis.


Thyroid cancer was diagnosed in 16 women (11.4%) and 2 men (1.4%), at 17–41 years and 39–57 years of age, respectively. The prevalence of thyroid cancer was 6.4%, with a female-to-male ratio of 8:1, which is comparable to reports from other countries. A young age of < 33 years at the FAP diagnosis and female gender were identified as independent risk factors for thyroid cancer.


FAP-associated thyroid cancer predominantly affects young women, both in Japan and other countries. Since FAP is generally diagnosed when patients are in their 20 s or older, regular screening for thyroid cancer is recommended for all FAP patients, but especially women, from their early 20 s.


Familial adenomatous polyposis Meta-analysis Prevalence Risk factor Thyroid cancer 



We appreciate the support with our statistical analyses, given by Minoru Hattori, Advanced Medical Skills Training Center, Hiroshima University, and we thank the Japanese Society for Cancer of Colon and Rectum (JSCCR) for their cooperation.

Compliance with ethical standards

Conflict of interest

We have no conflicts of interest to declare.


  1. 1.
    Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, et al. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science. 1991;253:665–9.CrossRefGoogle Scholar
  2. 2.
    Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM, Levy DB, et al. Identification of FAP locus genes from chromosome 5q21. Science. 1991;253:661–5.CrossRefGoogle Scholar
  3. 3.
    Bulow S. Results of national registration of familial adenomatous polyposis. Gut. 2003;52:742–6.CrossRefGoogle Scholar
  4. 4.
    Burn J, Chapman P, Delhanty J, Wood C, Lalloo F, Cachon-Gonzalez MB, et al. The UK Northern region genetic register for familial adenomatous polyposis coli: use of age of onset, congenital hypertrophy of the retinal pigment epithelium, and DNA markers in risk calculations. J Med Genet. 1991;28:289–96.CrossRefGoogle Scholar
  5. 5.
    Jarvinen HJ. Epidemiology of familial adenomatous polyposis in Finland: impact of family screening on the colorectal cancer rate and survival. Gut. 1992;33:357–60.CrossRefGoogle Scholar
  6. 6.
    Bulow S, Faurschou Nielsen T, Bülow C, Bisgaard ML, Karlsen L, Moesgaard F. The incidence rate of familial adenomatous polyposis. Results from the Danish Polyposis Register. Int J Colorectal Dis. 1996;11:88–91.CrossRefGoogle Scholar
  7. 7.
    HJR B. Familial polyposis coli. Baltimore: Johns Hopkins University Press; 1975.Google Scholar
  8. 8.
    Iwama T, Tamura K, Morita T, Hirai T, Hasegawa H, Koizumi K, et al. A clinical overview of familial adenomatous polyposis derived from the database of the Polyposis Registry of Japan. Int J Clin Oncol. 2004;9:308–16. Scholar
  9. 9.
    Nieuwenhuis MH, De VTotN Cappel, Botma W, Nagengast A, Kleibeuker FM, Mathus-Vliegen JH. EM, et al. Desmoid tumors in a dutch cohort of patients with familial adenomatous polyposis. Clin Gastroenterol Hepatol. 2008;6:215–9. Scholar
  10. 10.
    Maehata Y, Esaki M, Hirahashi M, Kitazono T, Matsumoto T. Duodenal adenomatosis in Japanese patients with familial adenomatous polyposis. Dig Endosc. 2014;26(Suppl 2):30–4. Scholar
  11. 11.
    Plail RO, Bussey HJ, Glazer G, Thomson JP. Adenomatous polyposis: an association with carcinoma of the thyroid. Br J Surg. 1987;74:377–80.CrossRefGoogle Scholar
  12. 12.
    Giardiello FM, Offerhaus GJ, Lee DH, Krush AJ, Tersmette AC, Booker SV, et al. Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut. 1993;34:1394–6.CrossRefGoogle Scholar
  13. 13.
    Iwama T, Mishima Y, Utsunomiya J. The impact of familial adenomatous polyposis on the tumorigenesis and mortality at the several organs. Its rational treatment. Ann Surg. 1993;217:101–8.CrossRefGoogle Scholar
  14. 14.
    Bulow C, Bulow S. Is screening for thyroid carcinoma indicated in familial adenomatous polyposis? The Leeds Castle Polyposis Group. Int J Colorectal Dis. 1997;12:240–2.CrossRefGoogle Scholar
  15. 15.
    Truta B, Allen BA, Conrad PG, Kim YS, Berk T, Gallinger S, et al. Genotype and phenotype of patients with both familial adenomatous polyposis and thyroid carcinoma. Fam Cancer. 2003;2:95–9.CrossRefGoogle Scholar
  16. 16.
    Harach HR, Williams GT, Williams ED. Familial adenomatous polyposis associated thyroid carcinoma: a distinct type of follicular cell neoplasm. Histopathology. 1994;25:549–61.CrossRefGoogle Scholar
  17. 17.
    Cameselle-Teijeiro J, Chan JK. Cribriform-morular variant of papillary carcinoma: a distinctive variant representing the sporadic counterpart of familial adenomatous polyposis-associated thyroid carcinoma? Mod Pathol. 1999;12:400–11.PubMedGoogle Scholar
  18. 18.
    Soravia C, Sugg SL, Berk T, Mitri A, Cheng H, Gallinger S, et al. Familial adenomatous polyposis-associated thyroid cancer: a clinical, pathological, and molecular genetics study. Am J Pathol. 1999;154:127–35. Scholar
  19. 19.
    Bulow S, Holm NV, Mellemgaard A. Papillary thyroid carcinoma in Danish patients with familial adenomatous polyposis. Int J Colorectal Dis. 1988;3:29–31.CrossRefGoogle Scholar
  20. 20.
    Perrier ND, van Heerden JA, Goellner JR, Williams ED, Gharib H, Marchesa P, et al. Thyroid cancer in patients with familial adenomatous polyposis. World J Surg. 1998; 22:738–42 (discussion 743).CrossRefGoogle Scholar
  21. 21.
    van der Linde K, Vasen HF, van Vliet AC. Occurrence of thyroid carcinoma in Dutch patients with familial adenomatous polyposis. An epidemiological study and report of new cases. Eur J Gastroenterol Hepatol. 1998;10:777–81.CrossRefGoogle Scholar
  22. 22.
    Herraiz M, Barbesino G, Faquin W, Chan-Smutko G, Patel D, Shannon KM, et al. Prevalence of thyroid cancer in familial adenomatous polyposis syndrome and the role of screening ultrasound examinations. Clin Gastroenterol Hepatol. 2007;5:367–73. Scholar
  23. 23.
    Jarrar AM, Milas M, Mitchell J, Laguardia L, O’Malley M, Berber E, et al. Screening for thyroid cancer in patients with familial adenomatous polyposis. Ann Surg. 2011;253:515–21. Scholar
  24. 24.
    Steinhagen E, Guillem JG, Chang G, Salo-Mullen EE, Shia J, Fish S, et al. The prevalence of thyroid cancer and benign thyroid disease in patients with familial adenomatous polyposis may be higher than previously recognized. Clin Colorectal Cancer. 2012;11:304–8. Scholar
  25. 25.
    Steinhagen E, Hui VW, Levy RA, Markowitz AJ, Fish S, Wong RJ, et al. Results of a prospective thyroid ultrasound screening program in adenomatous polyposis patients. Am J Surg. 2014;208:764–9. Scholar
  26. 26.
    Hizawa K, Iida M, Aoyagi K, Yao T, Fujishima M. Thyroid neoplasia and familial adenomatous polyposis/Gardner’s syndrome. J Gastroenterol. 1997;32:196–9.CrossRefGoogle Scholar
  27. 27.
    Ueno H, Kobayashi H, Konishi T, Ishida F, Yamaguchi T, Hinoi T, et al. Prevalence of laparoscopic surgical treatment and its clinical outcomes in patients with familial adenomatous polyposis in Japan. Int J Clin Oncol. 2016;21:713–22. Scholar
  28. 28.
    Ho JW, Chu KM, Tse CW, Yuen ST. Phenotype and management of patients with familial adenomatous polyposis in Hong Kong: perspective of the Hereditary Gastrointestinal Cancer Registry. Hong Kong Med J. 2002;8:342–7.PubMedGoogle Scholar
  29. 29.
    Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA. 2006;295:2164–7. Scholar
  30. 30.
    Saika K, Matsuda T, Sobue T. Incidence rate of thyroid cancer by histological type in Japan. Jpn J Clin Oncol. 2014;44:1131–2. Scholar
  31. 31.
    Matsuda A, Matsuda T, Shibata A, Katanoda K, Sobue T, Nishimoto H, et al. Cancer incidence and incidence rates in Japan in 2008: a study of 25 population-based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project. Jpn J Clin Oncol. 2014;44:388–96. Scholar
  32. 32.
    Kennedy RD, Potter DD, Moir CR, El-Youssef M. The natural history of familial adenomatous polyposis syndrome: a 24 year review of a single center experience in screening, diagnosis, and outcomes. J Pediatr Surg. 2014;49:82–6. Scholar
  33. 33.
    Uchino S, Ishikawa H, Miyauchi A, Hirokawa M, Noguchi S, Ushiama M, et al. Age- and gender-specific risk of thyroid cancer in patients with familial adenomatous polyposis. J Clin Endocrinol Metab. 2016;101:4611–7.CrossRefGoogle Scholar
  34. 34.
    Septer S, Slowik V, Morgan R, Dai H, Attard T. Thyroid cancer complicating familial adenomatous polyposis: mutation spectrum of at-risk individuals. Hered Cancer Clin Pract. 2013;11:13. Scholar
  35. 35.
    Nieuwenhuis MH, Bülow S, Bjork J, Jarvinen HJ, Bülow C, Bisgaard ML, et al. Genotype predicting phenotype in familial adenomatous polyposis: a practical application to the choice of surgery. Dis Colon Rectum. 2009;52:1259–63. Scholar
  36. 36.
    Groen EJ, Roos A, Muntinghe FL, Enting RH, de Vries J, Kleibeuker JH, et al. Extra-intestinal manifestations of familial adenomatous polyposis. Ann Surg Oncol. 2008;15:2439–50. Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Haruki Sada
    • 1
  • Takao Hinoi
    • 1
    • 12
    Email author
  • Hideki Ueno
    • 2
  • Tatsuro Yamaguchi
    • 3
  • Yasuhiro Inoue
    • 4
  • Tsuyoshi Konishi
    • 5
  • Hirotoshi Kobayashi
    • 6
  • Yukihide Kanemitsu
    • 7
  • Fumio Ishida
    • 8
  • Hideyuki Ishida
    • 9
  • Naohiro Tomita
    • 10
  • Nagahide Matsubara
    • 10
  • Kenichi Sugihara
    • 11
  1. 1.Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
  2. 2.Department of SurgeryNational Defense Medical CollegeSaitamaJapan
  3. 3.Department of SurgeryTokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalTokyoJapan
  4. 4.Department of Gastrointestinal and Pediatric SurgeryMie University Graduate School of MedicineTsuJapan
  5. 5.Gastroenterological Center, Department of Gastroenterological Surgery, Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyoJapan
  6. 6.Department of SurgeryTokyo Metropolitan Hiroo HospitalTokyoJapan
  7. 7.Division of Colorectal SurgeryNational Cancer Center HospitalTokyoJapan
  8. 8.Digestive Disease CenterShowa University Northern Yokohama HospitalYokohamaJapan
  9. 9.Department of Digestive Tract and General Surgery, Saitama Medical CenterSaitama Medical UniversitySaitamaJapan
  10. 10.Division of Lower GI Surgery, Department of SurgeryHyogo College of MedicineNishinomiyaJapan
  11. 11.Tokyo Medical and Dental UniversityTokyoJapan
  12. 12.Department of Surgery, Institute for Clinical ResearchNational Hospital Organization Kure Medical Center and Chugoku Cancer CenterHiroshimaJapan

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