A clinical and genetic analysis of multiple primary cancer referrals to genetics services
- 24 September 2014
- journal article
- research article
- Published by Springer Science and Business Media LLC in European Journal of Human Genetics
- Vol. 23 (5), 581-587
- https://doi.org/10.1038/ejhg.2014.157
Abstract
Multiple primary malignant tumours (MPMT) are frequently taken as an indicator of potential inherited cancer susceptibility and occur at appreciable frequency both among unselected cancer patients and, particularly, among referrals to cancer genetics services. However, there is a paucity of information on the clinical genetic evaluation of cohorts of MPMT patients representing a variety of tumour types. We ascertained a referral-based series of MPMT cases and describe the patterns of tumours observed. Service-based molecular genetic testing had demonstrated a pathogenic germline variant in an inherited cancer gene in fewer than one in four unselected referrals. To assess for evidence of thus far unidentified variants in those who tested negative, comparisons were made with those who tested positive. This revealed considerable overlap between the two groups with respect to clinical characteristics indicative of an inherited cancer syndrome. We therefore proceeded to test a subset of unexplained MPMT cases (n = 62) for pathogenic germline variants in TP53 and PTEN but none were detected. Individuals with MPMT may receive negative genetic test results for a number of reasons, which are discussed. Many of these may be addressed by the increasing application of next generation sequencing techniques such as inherited cancer gene panels.Keywords
This publication has 31 references indexed in Scilit:
- Lack of referral for genetic counseling and testing in BRCA1/2 and Lynch syndromes: a nationwide study based on 240,134 consultations and 134,652 genetic testsBreast Cancer Research and Treatment, 2013
- Risks of Colorectal and Other Cancers After Endometrial Cancer for Women With Lynch SyndromeJNCI Journal of the National Cancer Institute, 2013
- SomaticHIF2AGain-of-Function Mutations in Paraganglioma with PolycythemiaThe New England Journal of Medicine, 2012
- Variation of Second Cancer Risk by Family History of Retinoblastoma Among Long-Term SurvivorsJournal of Clinical Oncology, 2012
- Multiple tumours in survival estimatesEuropean Journal of Cancer, 2009
- Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relativesGenetics in Medicine, 2009
- Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995–99: results of the EUROCARE-4 studyThe Lancet Oncology, 2007
- Germline PTEN mutations are rare and highly penetrantHereditary Cancer in Clinical Practice, 2006
- Relative frequency and morphology of cancers in STK11 mutation carriersGastroenterology, 2004
- A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPROJournal of Medical Genetics, 2004