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Cancer risk and overall survival in mismatch repair proficient hereditary non-polyposis colorectal cancer, Lynch syndrome and sporadic colorectal cancer

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Abstract

Mismatch repair proficient hereditary non-polyposis colorectal cancer (MSS-HNPCC) encloses a heterogeneous group of families consisting of different unknown genetic syndromes and/or aggregations cases. The lack of information about the hereditability of cancer risk in these families makes it difficult to carry out an individualized Genetic Counseling. Therefore, deep description of such families becomes important for a better classification and search for underlying susceptibility causes. The aim of this study is to describe and compare the clinical, morphological features, tumor KRAS status and overall survival in MSS-HNPCC, Lynch and sporadic colorectal cancer. A total of 37 MSS-HNPCC families, 50 Lynch families and 612 sporadic CRC were included. Clinical and morphological data were evaluated by reviewing medical and pathology reports of 55, 69 and 102 tumors respectively. KRAS/BRAF status were detected by allele specific real-time PCR. Standardized incidence ratios (SIR) were calculated among 602 MSS-HNPCC relatives and 668 Lynch relatives. Main features distinguishing MSS-HNPCC were diagnosis age (55.1 ± 12.6), preferential distal location (76 %), polyp detection (45 %) and familial colorectal cancer incidence (SIR = 6.6). In addition, we found increased incidences rates for kidney, stomach and uterus tumors. KRAS mutation rates were similar in the study populations (48.8 ± 5.8) but higher than those described before by Sanger sequencing. MSS-HNPCC overall survival was similar to Lynch in B Dukes’ stage tumors and between Lynch and sporadic in C stage tumors. Anatomical and morphological data of MSS-HNPCC are consistent with other described populations. Our studies disclose an increased HNPCC-extracolonic tumors incidence and improved overall survival in MSS-HNPCC families.

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Acknowledgments

The present study was supported by the “Instituto de Salud Carlos III’’ (FEDER) research Grants FIS 10/00641 and RTICC 06/0020/0021, Spanish Ministry of Science.

Conflict of interest

All authors state that they have no conflicts of interest.

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Authors and Affiliations

  1. Laboratorio de Oncología Molecular, Servicio de Oncología Médica, Hospital Clínico San Carlos, IdISSC, c/Profesor Martín Lagos s/n, 28040, Madrid, Spain

    Pilar Garre, Lorena Martín, Inmaculada Bando, Alicia Tosar, Patricia Llovet, Atocha Romero, Miguel de la Hoya & Trinidad Caldés

  2. Servicio de Anatomía Patológica, Hospital Clínico San Carlos, IdISSC, c/Profesor Martín Lagos s/n, 28040, Madrid, Spain

    Julián Sanz

  3. Servicio de Oncología Médica, Hospital Clínico San Carlos, IdISSC, c/Profesor Martín Lagos s/n, 28040, Madrid, Spain

    Eduardo Díaz-Rubio

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  1. Pilar Garre
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Correspondence to Pilar Garre or Trinidad Caldés.

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Garre, P., Martín, L., Bando, I. et al. Cancer risk and overall survival in mismatch repair proficient hereditary non-polyposis colorectal cancer, Lynch syndrome and sporadic colorectal cancer. Familial Cancer 13, 109–119 (2014). https://doi.org/10.1007/s10689-013-9683-2

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