Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 51 (8), 545-52

High Risk of Tobacco-Related Cancers in CDKN2A Mutation-Positive Melanoma Families

Affiliations

High Risk of Tobacco-Related Cancers in CDKN2A Mutation-Positive Melanoma Families

Hildur Helgadottir et al. J Med Genet.

Abstract

Background: Germline mutations in the tumour suppressor gene CDKN2A occur in 5-20% of familial melanoma cases. A single founder mutation, p.Arg112dup, accounts for the majority of CDKN2A mutations in Swedish carriers. In a national program, carriers of p.Arg112dup mutation have been identified. The aim of this study was to assess cancer risks in p.Arg112dup carriers and their first degree relatives (FDRs) and second degree relatives (SDRs).

Methods: In this prospective cohort study, cancer diagnoses in carriers (n=120), non-carriers (n=111), carriers' FDRs (n=275) and SDRs (n=321) and controls (n=3976) were obtained from the Swedish Cancer Registry. Relative risks (RRs) for cancers were calculated (number of cancers/person years). Two-sided 95% CIs were calculated for all RRs.

Results: In carriers prospective RR for non-melanoma cancers was 5.0 (95% CI 3.7 to 7.3), for pancreatic cancer 43.8 (95% CI 13.8 to 139.0), for cancers in upper digestive tissues 17.1 (95% CI 6.3 to 46.5), and in respiratory tissues 15.6 (5.4 to 46.0). In FDRs and SDRs RRs were significantly elevated for cancers in pancreas, respiratory and upper digestive tissues. In ever-smoking carriers compared with never-smoking carriers, the odds ratio (OR) of cancers in pancreas, respiratory or upper digestive tissues was 9.3 (95% CI 1.9 to 44.7).

Conclusions: CDKN2A p.Arg112dup mutation carriers from melanoma-prone families and their FDRs and SDRs have elevated risk for pancreatic, lung, head and neck and gastro-oesophageal carcinomas. These cancers were mainly seen in ever-smoking carriers. Germline CDKN2A mutations may confer an increased sensitivity to carcinogens in tobacco smoke. CDKN2A mutation carriers should be counselled to abstain from smoking.

Keywords: Cancer: dermatological; Cancer: head and neck; Cancer: lung; Genetic epidemiology; Genetic screening/counselling.

Figures

Figure 1
Figure 1
Age-specific cumulative incidence of non-melanoma cancers and for cancers in respiratory and upper digestive tissues (including pancreas) among the cohort of CDKN2A p.Arg112dup carriers (n=120).

Similar articles

See all similar articles

Cited by 21 PubMed Central articles

See all "Cited by" articles

References

    1. Greene MH, Fraumeni JF. The hereditary variant of malignant melanoma. New York: Grune & Stratton, 1979
    1. Skolnick MH, Cannon-Albright LA, Kamb A. Genetic predisposition to melanoma. Eur J Cancer 1994;30A:1991–5 - PubMed
    1. Goldstein AM, Struewing JP, Chidambaram A, Fraser MC, Tucker MA. Genotype-phenotype relationships in u.S. Melanoma-prone families with cdkn2a and cdk4 mutations . J Natl Cancer Inst 2000;92:1006–10 - PubMed
    1. Borg A, Sandberg T, Nilsson K, Johannsson O, Klinker M, Masback A, Westerdahl J, Olsson H, Ingvar C. High frequency of multiple melanomas and breast and pancreas carcinomas in cdkn2a mutation-positive melanoma families. J Natl Cancer Inst 2000;92:1260–6 - PubMed
    1. Platz A, Hansson J, Mansson-Brahme E, Lagerlof B, Linder S, Lundqvist E, Sevigny P, Inganas M, Ringborg U. Screening of germline mutations in the cdkn2a and cdkn2b genes in swedish families with hereditary cutaneous melanoma. J Natl Cancer Inst 1997;89:697–702 - PubMed

Publication types

Substances

Feedback