Top

13-12-2017 | Colorectal cancer | Article

Prevalence and characteristics of hereditary non-polyposis colorectal cancer (HNPCC) syndrome in immigrant Asian colorectal cancer patients

Journal: BMC Cancer

Authors: Jasmine Lee, Yin-Yi Xiao, Yan Yu Sun, Jasminka Balderacchi, Bradley Clark, Jatin Desani, Vivek Kumar, Angela Saverimuthu, Khin Than Win, Yiwu Huang, Yiqing Xu

Publisher: BioMed Central

Abstract

Background

The prevalence of Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is 2 to 5% in the Caucasian population. HNPCC is caused by genomic mutations in DNA mismatch repair genes (MMR), namely MLH1, MSH2, MSH6, PMS2, and EPCAM. A non-hereditary, acquired process of hypermethylation of the MLH1 promoter can also lead to silencing of MLH1 protein expression. Diagnosis of HNPCC in patients with colorectal and other related cancers is important in the clinical treatment and surveillance of related cancers. The prevalence and clinical characteristics of HNPCC in Asian colorectal cancer patients has been reported in small studies and unique features have been suggested.

Methods

We retrospectively reviewed the clinical characteristics of Asian patients who were diagnosed of colon cancer between 1/2002 and 6/2015, and performed IHC for four MMR protein expressions on tumor specimens as a screening test for HNPCC, followed by confirmatory tests of genomic sequencing and hypermethylation analysis.

Results

One hundred forty-three patients were identified. Thirty-one patients were diagnosed younger than 50 years old, while 112 patients were diagnosed older than 50 years old. Six cases of HNPCC were found with a prevalence of 4.19%. The prevalence in the group of patients diagnosed younger than 50 years old is 16.1%, and that in patients diagnosed older than 50 years old is 0.89%. All patients with HNPCC had family histories of colon or gastric cancer. Tumor locations in the HNPCC patients were predominantly in the descending or sigmoid colon (67%). Half of the HNPCC patients had MSH6 mutations. Hypermethylation of the MLH1 gene was only present in 2.80% of the patients.

Conclusion

The prevalence of HNPCC is high in patients younger than 50 years old and extremely low in those older than 50 years old. These results may be useful in the future development of guidelines for HNPCC laboratory screening among Asian patients. The pathological and clinical features of HNPCC in this group of Asian immigrant patients are more similar to those reported on Asian patients in their home countries than to Caucasian patients in Western countries, and will warrant further large-scale evaluation.

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

Tutlewska K, Lubinski J, Kurzawski G. Germline deletions in the EPCAM gene as a cause of lynch syndrome - literature review. Hered Cancer Clin Pract. 2013;11(1):9.CrossRefPubMedPubMedCentral

Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, et al. A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58(22):5248–57.PubMed

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

Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Clendenning M, Sotamaa K, Prior T, Westman JA, et al. Feasibility of screening for lynch syndrome among patients with colorectal cancer. J Clin Oncol. 2008;26(35):5783–8.CrossRefPubMedPubMedCentral

Kane MF, Loda M, Gaida GM, Lipman J, Mishra R, Goldman H, Jessup JM, Kolodner R. Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res. 1997;57(5):808–11.PubMed

Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, et al. Screening for the lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med. 2005;352(18):1851–60.CrossRefPubMed

Domingo E, Laiho P, Ollikainen M, Pinto M, Wang L, French AJ, Westra J, Frebourg T, Espin E, Armengol M, et al. BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing. J Med Genet. 2004;41(9):664–8.CrossRefPubMedPubMedCentral

Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP, et al. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010;17(5):510–22.CrossRefPubMedPubMedCentral

10.

Gatalica Z, Vranic S, Xiu J, Swensen J, Reddy S. High microsatellite instability (MSI-H) colorectal carcinoma: a brief review of predictive biomarkers in the era of personalized medicine. Familial Cancer. 2016;15(3):405–12.CrossRefPubMedPubMedCentral

11.

Smyrk TC, Watson P, Kaul K, Lynch HT. Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma. Cancer. 2001;91(12):2417–22.CrossRefPubMed

12.

Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, Hamilton SR, Laurent-Puig P, Gryfe R, Shepherd LE, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003;349(3):247–57.CrossRefPubMedPubMedCentral

13.

Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20.CrossRefPubMedPubMedCentral

14.

Aaltonen LA, Salovaara R, Kristo P, Canzian F, Hemminki A, Peltomaki P, Chadwick RB, Kaariainen H, Eskelinen M, Jarvinen H, et al. Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med. 1998;338(21):1481–7.CrossRefPubMed

15.

Colon Cancer. In: Clinical Practice Guidelines in Oncology (NCCN Guidelines). National Comprehensive Cancer Network. 2017. https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed 29 Nov 2017.

16.

Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, Fishel R, Lindor NM, Burgart LJ, Hamelin R, et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96(4):261–8.CrossRefPubMedPubMedCentral

17.

Jin HY, Liu X, Li VK, Ding Y, Yang B, Geng J, Lai R, Ding S, Ni M, Zhao R. Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer. BMC Cancer. 2008;8:44.CrossRefPubMedPubMedCentral

18.

Chew MH, Koh PK, Ng KH, Lim JF, Ho KS, Ooi BS, Tang CL, Eu KW. Phenotypic characteristics of hereditary non-polyposis colorectal cancer by the Amsterdam criteria: an Asian perspective. ANZ J Surg. 2008;78(7):556–60.CrossRefPubMed

19.

Chew MH, Tan WS, Liu Y, Cheah PY, Loi CT, Tang CL. Genomics of hereditary colorectal cancer: lessons learnt from 25 years of the Singapore polyposis registry. Ann Acad Med Singap. 2015;44(8):290–6.PubMed

20.

Talseth-Palmer BA, McPhillips M, Groombridge C, Spigelman A, Scott RJ. MSH6 and PMS2 mutation positive Australian lynch syndrome families: novel mutations, cancer risk and age of diagnosis of colorectal cancer. Hered Cancer Clin Pract. 2010;8(1):5.CrossRefPubMedPubMedCentral

21.

Ho JW, Wei R, Chan EM. Hereditary colorectal cancer syndromes in Hong Kong: a Registry's perspective. Hered Cancer Clin Pract. 2005;3(4):147–54.CrossRefPubMedPubMedCentral

22.

Yan HL, Hao LQ, Jin HY, Xing QH, Xue G, Mei Q, He J, He L, Sun SH. Clinical features and mismatch repair genes analyses of Chinese suspected hereditary non-polyposis colorectal cancer: a cost-effective screening strategy proposal. Cancer Sci. 2008;99(4):770–80.CrossRefPubMed

23.

Liu F, Yang L, Zhou X, Sheng W, Cai S, Liu L, Nan P, Xu Y. Clinicopathological and genetic features of Chinese hereditary nonpolyposis colorectal cancer (HNPCC). Med Oncol. 2014;31(10):223.CrossRefPubMedPubMedCentral

24.

ND VAP, Innocenti F, Fruth B, Greene C, O’Neil BH, Shaw JE, Atkins JN, Horvath LE, Polite BN, et al. Impact of primary (1°) tumor location on overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): analysis of CALGB/SWOG 80405 (alliance). J Clin Oncol. 2016;34(15):3504.

25.

Tejpar S, Stintzing S, Ciardiello F, Tabernero J, Van Cutsem E, Beier F, Esser R, Lenz HJ, Heinemann V. Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials. JAMA Oncol. 2016;3:194–201.

26.

Siegel RL, Fedewa SA, Anderson WF, Miller KD, Ma J, Rosenberg PS, Jemal A. Colorectal cancer incidence patterns in the United States, 1974–2013. J Natl Cancer Inst. 2017;109(8):djw322.

27.

Moreira L, Balaguer F, Lindor N, de la Chapelle A, Hampel H, Aaltonen LA, Hopper JL, Le Marchand L, Gallinger S, Newcomb PA, et al. Identification of lynch syndrome among patients with colorectal cancer. JAMA. 2012;308(15):1555–65.CrossRefPubMed

28.

Peltomaki P. Deficient DNA mismatch repair: a common etiologic factor for colon cancer. Hum Mol Genet. 2001;10(7):735–40.CrossRefPubMed

29.

Wagner A, Hendriks Y, Meijers-Heijboer EJ, de Leeuw WJ, Morreau H, Hofstra R, Tops C, Bik E, Brocker-Vriends AH, van Der Meer C, et al. Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch pedigree. J Med Genet. 2001;38(5):318–22.CrossRefPubMedPubMedCentral

30.

Shapiro MB, Senapathy P. RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucleic Acids Res. 1987;15(17):7155–74.CrossRefPubMedPubMedCentral