title: CHEK2*1100delC and risk of malignant melanoma: Danish and German studies and meta-analysis.
abstract: It is possible that reduced function of DNA repair and cell-cycle control genes increases the individual susceptibility to malignant melanoma. As CHEK2 is a cell-cycle master controller, we tested the hypothesis that heterozygosity for the frameshift alteration CHEK2*1100delC is associated with increased risk of malignant melanoma. First, we performed case-control studies of 1,152 Danish and 752 German individuals with malignant melanoma compared with 9,142 Danish and 3,718 German controls. Second, we performed a meta-analysis of CHEK2*1100delC and malignant melanoma, involving 2,619 cases and 17,481 controls. Third, we examined the risk of malignant melanoma associated with CHEK2*1100delC heterozygosity in an analysis stratified for sun exposure, as well as for subtype and location on the body. The odds ratios for malignant melanoma for CHEK2(*)1100del heterozygotes compared with those for noncarriers were 2.01 (95% confidence interval (CI), 1.03-3.91) in Danes, 1.42 (95% CI, 0.46-4.31) in Germans, and 1.79 (95% CI, 1.02-3.17) in Danes and Germans combined. In a meta-analysis, the odds ratio of malignant melanoma for CHEK2*1100delC heterozygotes compared with that for noncarriers was 1.81 (95% CI, 1.07-3.05). Stratifications did not alter these results. CHEK2*1100delC heterozygotes have a twofold risk of malignant melanoma compared with noncarriers.
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Maren
authors.initials: M
authors.lastname: Weischer
authors.forename: Ida M
authors.initials: IM
authors.lastname: Heerfordt
authors.forename: Stig E
authors.initials: SE
authors.lastname: Bojesen
authors.forename: Thomas
authors.initials: T
authors.lastname: Eigentler
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.forename: Martin
authors.initials: M
authors.lastname: Röcken
authors.forename: Lisbet Rosenkrantz
authors.initials: LR
authors.lastname: Hölmich
authors.forename: Henrik
authors.initials: H
authors.lastname: Schmidt
authors.forename: Helle
authors.initials: H
authors.lastname: Klyver
authors.forename: Lars
authors.initials: L
authors.lastname: Bastholt
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D064447:Checkpoint Kinase 2; D003718:Denmark; D005260:Female; D005858:Germany; D006579:Heterozygote; D006801:Humans; D008297:Male; D008545:Melanoma / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics; D012307:Risk Factors; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*
chemical_list: D044102:Receptor, Melanocortin, Type 1; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases