Significance of defining a pathogenic variant in hereditary cancer syndrome

Kwong-Kwok Wong


With the advances in cancer genetics, over 200 hereditary cancer susceptibility syndromes have been described. About 5%–10% of all cancers are caused by hereditary mutations. The most common syndromes are those associated with breast, ovarian and gastrointestinal cancers. The hereditary pattern of stomach and endometrial cancer was first reported by Warthin in 1931. In 1966, Lynch and colleagues reported studies of two extended pedigrees with a similar hereditary pattern of multiple carcinomas and this was designated a cancer family syndrome. This condition was subsequently called hereditary nonpolyposis colorectal cancer (HNPCC). However, the term “Lynch syndrome” has been commonly used to describe this condition since 1984.


Lynch syndrome; ClinVar; pedigree analysis; endometrial cancer; MLH1 gene variants

Full Text:



Nagy R, Sweet K, Eng C. Highly penetrant hereditary cancer syndromes. Oncogene 2004; 23(38): 6445–6470. doi: 10.1038/sj.onc.1207714.

Amberger JS, Bocchini CA, Schiettecatte F, Scott AF, Hamosh A. Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders. Nucleic Acids Res 2015; 43(DI): D789–D798. doi: 10.1093/nar/gku1205.

Warthin AS. Heredity of carcinoma in man. Ann Intern Med 1931; 4(7): 681–696. doi: 10.7326/0003-4819-4-7-681.

Lynch HT, Shaw MW, Magnuson CW, Larsen AL, Krush AJ. Hereditary factors in cancer. Study of two large midwestern kindreds. Arch Intern Med 1966; 117(2): 206–212. doi: 10.1001/archinte.1966.03870080050009.

Boland CR, Troncale FJ. Familial colonic cancer without antecedent polyposis. Ann Intern Med 1984; 100(5): 700–701. doi: 10.7326/0003-4819-100-5-700

Lu KH, Dinh M, Kohlmann W, Watson P, Green J, et al. Gynecologic cancer as a sentinel cancer for women with hereditary nonpolyposis colorectal cancer syndrome. Obstet Gynecol 2005; 105(3): 569–574. doi: 10.1097/

Huang F, Tao X, Jiang W, Chen J, Feng W. Identification and verification of a pathogenic MLH1 Mutation c.1145dupA in a Lynch syndrome family. Adv Mod Oncol Res 2017; 3(3). doi: 10.18282/amor.v3.i3.213. (In Press)

Landrum MJ, Lee JM, Benson M, Brown G, Chao C, et al. ClinVar: Public archive of interpretations of clinically relevant variants. Nucleic Acids Res 2016; 44(D1): D862–D868. doi: 10.1093/nar/gkv1222.

Richards S, Aziz N, Bale S, Bick D, Das S, et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17(5): 405–424. doi: 10.1038/gim.2015.30.

Hunter JE, Arnold KA, Cook JE, Zepp J, Gilmore MJ, et al. Universal screening for Lynch syndrome among patients with colorectal cancer: Patient perspectives on screening and sharing results with at-risk relatives. Fam Cancer 2017. doi: 10.1007/s10689-017-9972-2.

Watkins JC, Yang EJ, Muto MG, Feltmate CM, Berkowitz RS, et al. Universal screening for mismatch-repair deficiency in endometrial cancers to identify patients with Lynch syndrome and Lynch-like syndrome. Int J Gynecol Pathol 2017; 36(2): 115–127. doi: 10.1097/PGP.0000000000000312.

Hampel H. Genetic counseling and cascade genetic testing in Lynch syndrome. Fam Cancer 2016; 15(3): 423–427. doi: 10.1007/s10689-016-9893-5.

Yurgelun MB, Chenevix-Trench G, Lippman SM. Translating germline cancer risk into precision prevention. Cell 2017; 168(4): 566–570. doi: 10.1016/j.cell.2017.01.031.



  • There are currently no refbacks.

Copyright (c) 2018 Kwong-Kwok Wong

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.