Longer Telomeres Are Associated with Cancer Risk in MMR-Proficient Hereditary Non-Polyposis Colorectal Cancer

Aberrant telomere length measured in blood has been associated with increased risk of several cancer types. In the field of hereditary non-polyposis colorectal cancer (CRC), and more particularly in Lynch syndrome, caused by germline mutations in the mismatch repair (MMR) genes, we recently found that cancer-affected MMR gene mutation carriers had shorter telomeres and more pronounced shortening of telomere length with age than controls and unaffected MMR gene mutation carriers. Here we evaluate blood telomere length in MMR-proficient hereditary non-polyposis CRC, i.e. familial CRC type X (fCRC-X). A total of 57 cancer-affected and 57 cancer-free individuals from 34 Amsterdam-positive fCRC-X families were analyzed and compared to the data previously published on 144 cancer-affected and 100 cancer-free MMR gene mutation carriers, and 234 controls. Relative telomere length was measured using a monochrome multiplex quantitative PCR method, following strict measures to avoid sources of bias and adjusting by age. Despite the retrospective nature of our study, the results show that longer telomeres associate with cancer risk in fCRC-X, thus identifying different patterns of telomere length according to the status of the MMR system.

[1]  E. Guinó,et al.  Telomere Length and Genetic Anticipation in Lynch Syndrome , 2013, PloS one.

[2]  S. Chanock,et al.  The long and short of telomeres and cancer association studies. , 2013, Journal of the National Cancer Institute.

[3]  N. Rothman,et al.  Association of Leukocyte Telomere Length with Colorectal Cancer Risk: Nested Case–Control Findings from the Shanghai Women's Health Study , 2012, Cancer Epidemiology, Biomarkers & Prevention.

[4]  Y. Pawitan,et al.  Gene discovery in familial cancer syndromes by exome sequencing: prospects for the elucidation of familial colorectal cancer type X , 2012, Modern Pathology.

[5]  L. Hou,et al.  Surrogate tissue telomere length and cancer risk: shorter or longer? , 2012, Cancer letters.

[6]  L. Chin,et al.  Antitelomerase Therapy Provokes ALT and Mitochondrial Adaptive Mechanisms in Cancer , 2012, Cell.

[7]  S. Savage,et al.  Epidemiologic evidence for a role of telomere dysfunction in cancer etiology. , 2012, Mutation research.

[8]  C. Price,et al.  Maintaining the end: roles of telomere proteins in end-protection, telomere replication and length regulation. , 2012, Mutation research.

[9]  M. Ponz de Leòn,et al.  Analysis of telomere dynamics in peripheral blood cells from patients with Lynch syndrome , 2011, Cancer.

[10]  D. Talwar,et al.  Telomere Attrition and Decreased Fetuin-A Levels Indicate Accelerated Biological Aging and Are Implicated in the Pathogenesis of Colorectal Cancer , 2011, Clinical Cancer Research.

[11]  M. Urioste,et al.  Genetic Anticipation Is Associated with Telomere Shortening in Hereditary Breast Cancer , 2011, PLoS genetics.

[12]  S. Ballereau,et al.  TERC polymorphisms are associated both with susceptibility to colorectal cancer and with longer telomeres , 2011, Gut.

[13]  B. Ponder,et al.  Telomere length in prospective and retrospective cancer case-control studies. , 2010, Cancer research.

[14]  J. Buring,et al.  Mean leukocyte telomere length and risk of incident colorectal carcinoma in women: a prospective, nested case-control study , 2010, Clinical chemistry and laboratory medicine.

[15]  Nathaniel Rothman,et al.  A Prospective Study of Telomere Length Measured by Monochrome Multiplex Quantitative PCR and Risk of Non-Hodgkin Lymphoma , 2009, Clinical Cancer Research.

[16]  J. Buring,et al.  Mean Telomere Length and Risk of Incident Colorectal Carcinoma: A Prospective, Nested Case-Control Approach , 2009, Cancer Epidemiology, Biomarkers & Prevention.

[17]  H T Lynch,et al.  Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications , 2009, Clinical genetics.

[18]  P. Rosenberg,et al.  Cancer in dyskeratosis congenita. , 2009, Blood.

[19]  Richard M. Cawthon,et al.  Telomere length measurement by a novel monochrome multiplex quantitative PCR method , 2009, Nucleic acids research.

[20]  C. Heaphy,et al.  Telomeres: Prognostic markers for solid tumors , 2006, International journal of cancer.

[21]  M. Blasco.  Telomeres and human disease: ageing, cancer and beyond , 2005, Nature Reviews Genetics.

[22]  M. Blasco.  Mice with bad ends: mouse models for the study of telomeres and telomerase in cancer and aging , 2005, The EMBO journal.