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Malignant melanoma-Risk factors and the CDKN2A mutation in relation to phenotypes and other cancers.

Nielsen, Kari LU (2009) In Lund University, Faculty of Medicine Doctoral Dissertaion Series 2009:111.
Abstract
Background: Cutaneous malignant melanoma (CMM) is an increasingly common cancer in fair-skinned people. The purpose of this thesis was to study high-risk patients with multiple tumours including a CMM, high-risk families with the unique Swedish germline mutation in CDKN2A(113insArg), as well as study risk factors for CMM in women.

Methods: Tumours associated with CMM, in individuals/probands with four or more primary tumours including at least one CMM were genotyped. The probands were further sub-grouped according to subsequent cancers (Paper I). Possible similarities in tumour patterns were studied in their close relatives (Paper II*). Further, melanoma-prone families in southern Sweden with the 113insArg/CDKN2A mutation were... (More)
Background: Cutaneous malignant melanoma (CMM) is an increasingly common cancer in fair-skinned people. The purpose of this thesis was to study high-risk patients with multiple tumours including a CMM, high-risk families with the unique Swedish germline mutation in CDKN2A(113insArg), as well as study risk factors for CMM in women.

Methods: Tumours associated with CMM, in individuals/probands with four or more primary tumours including at least one CMM were genotyped. The probands were further sub-grouped according to subsequent cancers (Paper I). Possible similarities in tumour patterns were studied in their close relatives (Paper II*). Further, melanoma-prone families in southern Sweden with the 113insArg/CDKN2A mutation were phenotyped and genotyped (Paper III). Finally, a population-based cohort of originally 40.000 women was prospectively followed for 18 years regarding CMM after answering a questionnaire about CMM risk factors (Paper IV).

Results: Papers I-II: The mutation was overrepresented in probands with multiple CMM. Non-mutation probands presented e.g. Neural System Tumours (NSTs), adenocarcinomas and non-melanoma skin cancer (NMSC), which were also seen in their relatives. For the relatives an overall increased risk for cancer was seen. Paper III: Positive mutation status was associated with clinically atypical nevi (CAN), and CMM diagnosis with red hair colour and CAN. No CMM were diagnosed in non-mutation carriers. The overall total nevus count (median 12, IQR: 5-25) and rate of individuals affected by CAN (14%), were lower in these families than shown in previous, population-based, Swedish studies. No atypical mole syndrome (AMS) phenotype was seen. Paper IV: Family history and ≥1 nevus on the left arm were risk factors for CMM, irrespective of age of the participants. Younger women with a history of frequent sunbed use had an additionally increased risk for CMM. CMM on the trunk were associated with a family history of CMM, a high nevus number and the youngest age at diagnosis.

Conclusions: The 113insArg/CDKN2A mutation in these melanom-prone families is difficult to diagnose dermatologically, but the presence of CMM seems to be completely associated with the mutation. Hence, mutation carriers must be followed-up by dermatologists irrespective of phenotype. The population-based risks for CMM in southern Swedish women seem to be associated with a family history of CMM, a higher nevus number and, for younger women, the use of sunbeds. *Supplement. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • M.D., Professor Lindelöf, Bernt, Department of Dermatology and Venereology, Karolinska University Hospital and Karolinska Institute
organization
publishing date
type
Thesis
publication status
published
subject
keywords
clinically atypical nevus, nevus, CDKN2A, melanoma, risk factors, sunbed, UVR
in
Lund University, Faculty of Medicine Doctoral Dissertaion Series
volume
2009:111
pages
120 pages
publisher
Lund University, Faculty of Medicine
defense location
Segerfalksalen BMC A 10, Sölvegatan 17, 221 84 Lund
defense date
2009-11-20 13:00
ISSN
1652-8220
ISBN
978-91-86253-99-8
language
English
LU publication?
yes
id
2f01693f-4c95-4d8e-a1f5-3777a0e4ea35 (old id 1494438)
date added to LUP
2009-11-06 09:45:04
date last changed
2016-09-19 08:44:46
@phdthesis{2f01693f-4c95-4d8e-a1f5-3777a0e4ea35,
  abstract     = {Background: Cutaneous malignant melanoma (CMM) is an increasingly common cancer in fair-skinned people. The purpose of this thesis was to study high-risk patients with multiple tumours including a CMM, high-risk families with the unique Swedish germline mutation in CDKN2A(113insArg), as well as study risk factors for CMM in women. <br/><br>
Methods: Tumours associated with CMM, in individuals/probands with four or more primary tumours including at least one CMM were genotyped. The probands were further sub-grouped according to subsequent cancers (Paper I). Possible similarities in tumour patterns were studied in their close relatives (Paper II*). Further, melanoma-prone families in southern Sweden with the 113insArg/CDKN2A mutation were phenotyped and genotyped (Paper III). Finally, a population-based cohort of originally 40.000 women was prospectively followed for 18 years regarding CMM after answering a questionnaire about CMM risk factors (Paper IV). <br/><br>
Results: Papers I-II: The mutation was overrepresented in probands with multiple CMM. Non-mutation probands presented e.g. Neural System Tumours (NSTs), adenocarcinomas and non-melanoma skin cancer (NMSC), which were also seen in their relatives. For the relatives an overall increased risk for cancer was seen. Paper III: Positive mutation status was associated with clinically atypical nevi (CAN), and CMM diagnosis with red hair colour and CAN. No CMM were diagnosed in non-mutation carriers. The overall total nevus count (median 12, IQR: 5-25) and rate of individuals affected by CAN (14%), were lower in these families than shown in previous, population-based, Swedish studies. No atypical mole syndrome (AMS) phenotype was seen. Paper IV: Family history and ≥1 nevus on the left arm were risk factors for CMM, irrespective of age of the participants. Younger women with a history of frequent sunbed use had an additionally increased risk for CMM. CMM on the trunk were associated with a family history of CMM, a high nevus number and the youngest age at diagnosis. <br/><br>
Conclusions: The 113insArg/CDKN2A mutation in these melanom-prone families is difficult to diagnose dermatologically, but the presence of CMM seems to be completely associated with the mutation. Hence, mutation carriers must be followed-up by dermatologists irrespective of phenotype. The population-based risks for CMM in southern Swedish women seem to be associated with a family history of CMM, a higher nevus number and, for younger women, the use of sunbeds. *Supplement.},
  author       = {Nielsen, Kari},
  isbn         = {978-91-86253-99-8},
  issn         = {1652-8220},
  keyword      = {clinically atypical nevus,nevus,CDKN2A,melanoma,risk factors,sunbed,UVR},
  language     = {eng},
  pages        = {120},
  publisher    = {Lund University, Faculty of Medicine},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertaion Series},
  title        = {Malignant melanoma-Risk factors and the CDKN2A mutation in relation to phenotypes and other cancers.},
  volume       = {2009:111},
  year         = {2009},
}