Oncology Medical News about CDKN2A, Cutaneous malignant melanoma

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Identification of modifier genes for cutaneous malignant melanoma in melanoma-prone families with and without CDKN2A mutations
International Journal of Cancer, 07/27/09

Yang XR et al. – These findings support the hypothesis that common genetic polymorphisms in DNA repair, apoptosis and immune response pathways may modify the risk of cutaneous malignant melanoma (CMM) in CMM-prone families with or without CDKN2A mutations.

Methods

Aim was to identify modifier genes for CMM in CMM-prone families with or w/o CDKN2A mutations
537 individuals (107 CMM) from 28 families (19 CDKN2A+, 9 CDKN2A-)
They were genotyped for 1,536 SNPs in 152 genes involved in DNA repair, apoptosis and immune response pathways
Conditional logistic regression: to account for family ascertainment and differences in disease prevalence among families
Pathway- and gene-based permutation analyses to assess the risk of CMM associated with genes in the 5 pathways: DNA repair, apoptosis, TNF/NFB, TH1:TH2 and other immune regulation

Results

Some candidate genes such as FAS, BCL7A, CASP14, TRAF6, WRN, IL9, IL10RB, TNFSF8, TNFRSF9 and JAK3 were associated with CMM risk
After correction for multiple comparisons, IL9 remained significant
Effects of some genes were stronger in CDKN2A-positive families (BCL7A and IL9); some were stronger in CDKN2A-negative families (BCL2L1)

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