International Journal of Hematology-Oncology and Stem Cell Research 2017. 11(3):241-246.

Familial Colorectal CancerType X in Central Iran: A New Clinicopathologic Description
Mehrdad Zeinalian, Mahdi Hadian, Morteza Hashemzadeh-Chaleshtori, Rasoul Salehi, Mohammad Hassan Emami

Abstract


Background: Familial colorectal cancer type X (FCCX) is a subtype of mismatchrepair (MMR)-proficient colorectal cancerin whichthe patients are clinicallyat risk for Lynch syndrome (LS), a common hereditary cancer predisposing syndrome.In this study, we describeda new clinicopathological feature of the condition in central Iran.

Subjects and Methods: We designed a descriptive, retrospective study to screenat-riskcolorectal cancer (CRC) patients,usingAmsterdam II criteria and Molecular analysis in Isfahan (central Iran) throughout 2000-2013 period.

Results: 219 early-onset (≤ 50 years) CRC patients of 1659 were selected for the evaluation. Amsterdam II criteria were positive in 45 families; of whom 31 were finally analyzed by molecular testing. 

MMR deficiency was detected in 7/31 probands (22.6%) as affected to LS, so 24 families (77.4%) were identified as FCCX. The mean age of the probands at diagnosis among FCCX families was 45.3 years (range 24-69) versus 38.0 years (range 31-50) in LS families.The frequency of CRC among FCCX and LS families was calculated 27.9% and 67.5%, respectively. Also, the most frequent extracolonic cancer among both FCCX and LS families was stomach by 25.5% and 30.8%, respectively. Tumor site was proximal to the splenic flexure in 20.8% and 57.1% of index CRC patients in FCCX and LS families, respectively.

Conclusion: Given the relative high frequency of FCCXand its different phenotype among Iranian populations, we need to set up more advanced molecular studies for exploration of unknown molecular pathways leading to tumorigenesis in this class of CRC patients.

 


Keywords


Familial colorectal cancer type X, Clinicopathologic, Lynch syndrome, Iran

Full Text:

PDF

References


Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg. 2009;22(4):191.

Rezaianzadeh A, Safarpour AR, Marzban M, et al. A Systematic Review Over the Incidence of Colorectal Cancer in Iran. Ann Colorectal Res. 2015;3(1):e25724.

Khorrami S, Zavaran Hosseini A, Mowla SJ, et al. Verification of ALDH Activity as a Biomarker in Colon Cancer Stem Cells-Derived HT-29 Cell Line. Iran J Cancer Prev. 2015;8(5):e3446.

Balmana J, Castells A, Cervantes A. Familial colorectal cancer risk: ESMO Clinical Practice Guidelines. Ann Oncol. 2010;5:v78–v81.

Patel SG, Ahnen DJ. Familial colon cancer syndromes: an update of a rapidly evolving field. Curr Gastroenterol Rep. 2012;14:428–38.

Woods M, Younghusband H, Parfrey P, et al. The genetic basis of colorectal cancer in a population-based incident cohort with a high rate of familial disease. Gut. 2010:gut. 2010.208462.

Vasen HF, Watson P, Mecklin JP, et al. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999 Jun;116(6):1453-6.

Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003;348(10):919-32.

Zeinalian M, Hashemzadeh-Chaleshtori M, Akbarpour MJ, et al. Epidemioclinical Feature of Early-Onset Colorectal Cancer at-Risk for Lynch Syndrome in Central Iran. Asian Pac J Cancer Prev. 2015;16(11):4647-52.

Rohlin A. Hereditary Colorectal Cancer; Identification, Characterization and Classification of Mutations. Doctoral thesis: University of Gothenburg. Sahlgrenska Academy.Institute of Biomedicine. Department of Medical Genetics. 2015.

Kastrinos F, Stoffel EM. History, genetics, and strategies for cancer prevention in Lynch syndrome. Clin Gastroenterol Hepatol. 2014;12(5):715-27.

Dominguez-Valentin M, Therkildsen C, Da Silva S, et al. Familial colorectal cancer type X: genetic profiles and phenotypic features. Mod Pathol. 2015 Jan;28(1):30-6.

Lynch HT, Lynch PM, Lanspa SJ, et al. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clinical genetics. 2009 Jul;76(1):1-18.

Boland CR, Koi M, Chang DK, et al. The biochemical basis of microsatellite instability and abnormal immunohistochemistry and clinical behavior in Lynch syndrome: from bench to bedside. Fam Cancer. 2008;7(1):41-52.

Zeinalian M, Emami MH, Naimi A, et al. Immunohistochemical analysis of mismatch repair proteins in Iranian colorectal cancer patients at risk for lynch syndrome. Iran J Cancer Prev. 2015 Jan-Feb;8(1):11-7.

Castillejo A, Vargas G, Castillejo MI, et al. Prevalence of germline MUTYH mutations among Lynch-like syndrome patients. Eur J Cancer. 2014 Sep;50(13):2241-50.

Carethers JM. Differentiating Lynch-like from Lynch syndrome. Gastroenterology. 2014 Mar;146(3):602-4.

Kang SY, Park CK, Chang DK, et al. Lynch-like syndrome: characterization and comparison with EPCAM deletion carriers. Int J Cancer. 2015 Apr 1;136(7):1568-78.

Shiovitz S, Copeland WK, Passarelli MN, et al. Characterisation of familial colorectal cancer Type X, Lynch syndrome, and non-familial colorectal cancer. Br J Cancer. 2014 Jul 29;111(3):598-602.

Yamaguchi T, Furukawa Y, Nakamura Y, et al. Comparison of clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients with colorectal cancer: a cross-sectional study conducted by the Japanese Society for Cancer of the Colon and Rectum. Jpn J Clin Oncol. 2014:hyu190.

Mahdavinia M, Bishehsari F, Ansari R, et al. Family history of colorectal cancer in Iran. BMC cancer. 2005;5:112.

Dolatkhah R, Somi MH, Bonyadi MJ, et al. Colorectal Cancer in Iran: Molecular Epidemiology and Screening Strategies. J Cancer Epidemiol. 2015;2015:10.

Fatemi SR, Pourhoseingholi MA, Asadi F, et al. Recurrence and Five -Year Survival in Colorectal Cancer Patients After Surgery. Iran J Cancer Prev. 2015;8(4):e3439.

Moreira L, Balaguer F, Lindor N, et al. Identification of Lynch syndrome among patients with colorectal cancer. Jama. 2012;308(15):1555-65.

Nieminen TT, Abdel–Rahman WM, Ristimäki A, et al. BMPR1A mutations in hereditary nonpolyposis colorectal cancer without mismatch repair deficiency. Gastroenterology. 2011;141(1):e23-e6.

Peltomäki P, Gao X, Mecklin J-P. Genotype and phenotype in hereditary nonpolyposis colon cancer: a study of families with different vs. shared predisposing mutations. Fam cancer. 2001;1(1):9-15.

Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology. 2010;138(6):2073-87. e3.

de la Chapelle A, Hampel H. Clinical relevance of microsatellite instability in colorectal cancer. J Clin Oncol. 2010;28(20):3380-7.

Jenkins MA, Southey MC, Giles GG, et al. Rationale for, and approach to, studying modifiers of risk in persons with a genetic predisposition to colorectal cancer. Curr Colorectal Cancer Rep. 2006;2(4):173-8.

Lindor NM. Familial colorectal cancer type X: the other half of hereditary nonpolyposis colon cancer syndrome. Surg Oncol Clin N Am. 2009 Oct;18(4):637-45.

Francisco I, Albuquerque C, Lage P, et al. Familial colorectal cancer type X syndrome: two distinct molecular entities? Fam cancer. 2011 Dec;10(4):623-31.

Lindor NM. Familial colorectal cancer type X: the other half of hereditary nonpolyposis colon cancer syndrome. Surg Oncol Clin N Am. 2009;18(4):637-45.

Lindor NM, Rabe K, Petersen GM, et al. Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. Jama. 2005 Apr 27;293(16):1979-85.

Lynch HT, Lynch JF, Attard TA. Diagnosis and management of hereditary colorectal cancer syndromes: Lynch syndrome as a model. CMAJ. 2009 Sep 1;181(5):273-80.

Mueller-Koch Y, Vogelsang H, Kopp R, et al. Hereditary non-polyposis colorectal cancer: clinical and molecular evidence for a new entity of hereditary colorectal cancer. Gut. 2005 Dec;54(12):1733-40.

Zeinalian M, Emami MH, Salehi R, et al. Molecular Analysis of Iranian Colorectal Cancer Patients at Risk for Lynch Syndrome: a New Molecular, Clinicopathological Feature.J Gastrointest Cancer. 2015 Feb 27;46(2):118-25.

Sehgal R, Sheahan K, O'Connell PR, et al. Lynch syndrome: an updated review. Genes. 2014;5(3):497-507.


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.