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Germline genetics of cancer of unknown primary (CUP) and its specific subtypes.

Hemminki, Kari LU ; Chen, Bowang; Kumar, Abhishek; Melander, Olle LU ; Manjer, Jonas LU ; Hallmans, Göran; Pettersson-Kymmer, Ulrika; Ohlsson, Claes; Folprecht, Gunnar and Löffler, Harald, et al. (2016) In Oncotarget 7(16). p.22140-22149
Abstract
Cancer of unknown primary site (CUP) is a fatal cancer diagnosed through metastases at various organs. Little is known about germline genetics of CUP which appears worth of a search in view of reported familial associations in CUP. In the present study, samples from CUP patients were identified from 2 Swedish biobanks and a German clinical trial, totaling 578 CUP patients and 7628 regionally matched controls. Diagnostic data specified the organ where metastases were diagnosed. We carried out a genome-wide association study on CUP cases and controls. In the whole sample set, 6 loci reached an allelic p-value in the range of 10-7 and were supported by data from the three centers. Three associations were located next to non-coding RNA genes.... (More)
Cancer of unknown primary site (CUP) is a fatal cancer diagnosed through metastases at various organs. Little is known about germline genetics of CUP which appears worth of a search in view of reported familial associations in CUP. In the present study, samples from CUP patients were identified from 2 Swedish biobanks and a German clinical trial, totaling 578 CUP patients and 7628 regionally matched controls. Diagnostic data specified the organ where metastases were diagnosed. We carried out a genome-wide association study on CUP cases and controls. In the whole sample set, 6 loci reached an allelic p-value in the range of 10-7 and were supported by data from the three centers. Three associations were located next to non-coding RNA genes. rs2660852 flanked 5'UTR of LTA4H (leukotriene A4 hydrolase), rs477145 was intronic to TIAM1 (T-cell lymphoma invasion and metastases) and rs2835931 was intronic to KCNJ6 (potassium channel, inwardly rectifying subfamily J, member 6). In analysis of subgroups of CUP patients (smokers, non-smokers and CUP with liver metastases) genome-wide significant associations were noted. For patients with liver metastases associations on chromosome 6 and 11, the latter including a cluster of genes DHCR7 and NADSYN1, encoding key enzymes in cholesterol and NAD synthesis, and KRTAP5-7, encoding a keratin associated protein. This first GWAS on CUP provide preliminary evidence that germline genes relating to inflammation (LTA4H), metastatic promotion (TIAM1) in association with lipid metabolic disturbance (chromosome 11 cluster) may contribute to the risk of CUP. (Less)
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Oncotarget
volume
7
issue
16
pages
22140 - 22149
publisher
Impact Journals, LLC
external identifiers
  • PMID:26959888
  • Scopus:84965014512
  • WOS:000377705900082
ISSN
1949-2553
DOI
10.18632/oncotarget.7903
language
English
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yes
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5885eeab-98a3-48ff-a55a-45fb28ea88b7 (old id 8852861)
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http://www.ncbi.nlm.nih.gov/pubmed/26959888?dopt=Abstract
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2016-03-16 15:13:38
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2017-02-12 04:23:14
@article{5885eeab-98a3-48ff-a55a-45fb28ea88b7,
  abstract     = {Cancer of unknown primary site (CUP) is a fatal cancer diagnosed through metastases at various organs. Little is known about germline genetics of CUP which appears worth of a search in view of reported familial associations in CUP. In the present study, samples from CUP patients were identified from 2 Swedish biobanks and a German clinical trial, totaling 578 CUP patients and 7628 regionally matched controls. Diagnostic data specified the organ where metastases were diagnosed. We carried out a genome-wide association study on CUP cases and controls. In the whole sample set, 6 loci reached an allelic p-value in the range of 10-7 and were supported by data from the three centers. Three associations were located next to non-coding RNA genes. rs2660852 flanked 5'UTR of LTA4H (leukotriene A4 hydrolase), rs477145 was intronic to TIAM1 (T-cell lymphoma invasion and metastases) and rs2835931 was intronic to KCNJ6 (potassium channel, inwardly rectifying subfamily J, member 6). In analysis of subgroups of CUP patients (smokers, non-smokers and CUP with liver metastases) genome-wide significant associations were noted. For patients with liver metastases associations on chromosome 6 and 11, the latter including a cluster of genes DHCR7 and NADSYN1, encoding key enzymes in cholesterol and NAD synthesis, and KRTAP5-7, encoding a keratin associated protein. This first GWAS on CUP provide preliminary evidence that germline genes relating to inflammation (LTA4H), metastatic promotion (TIAM1) in association with lipid metabolic disturbance (chromosome 11 cluster) may contribute to the risk of CUP.},
  author       = {Hemminki, Kari and Chen, Bowang and Kumar, Abhishek and Melander, Olle and Manjer, Jonas and Hallmans, Göran and Pettersson-Kymmer, Ulrika and Ohlsson, Claes and Folprecht, Gunnar and Löffler, Harald and Krämer, Alwin and Försti, Asta},
  issn         = {1949-2553},
  language     = {eng},
  month        = {03},
  number       = {16},
  pages        = {22140--22149},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Germline genetics of cancer of unknown primary (CUP) and its specific subtypes.},
  url          = {http://dx.doi.org/10.18632/oncotarget.7903},
  volume       = {7},
  year         = {2016},
}