Risk of other Cancers in Families with Melanoma: Novel Familial Links

Our plain-English summary of Risk of other Cancers in Families with Melanoma: Novel Familial Links, by C. Frank, J. Sundquist, A. Hemminki, et al (Scientific Reports, 2017).

The study

• Authors: C. Frank, J. Sundquist, A. Hemminki, K. Hemminki
• Journal: Scientific Reports
• Published: 2017;7:42601
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

A family history of cutaneous melanoma ('melanoma') is a well-established risk factor for melanoma. However, less is known about the possible familial associations of melanoma with other discordant cancers. A risk for discordant cancer may provide useful information about shared genetic and environmental risk factors and it may be relevant background data in clinical genetic counseling. Using the Swedish Family-Cancer Database, we assessed the relative risk (RR) for any cancer in families with increasing numbers of first-degree relatives diagnosed with melanoma, including multiple melanoma, and in reverse order RR for melanoma in families of multiple discordant cancers. Close to 9% of melanoma was familial; among these 92% were in 2-case families and 8% in families with 3 cases or more. Cancers that were associated with melanoma, in at least two independent analyses, included breast, prostate, colorectal, skin and nervous system cancers. Other associations included cancer of unknown primary, acute myeloid leukemia/myelofibrosis and Waldenström macroglobulinemia/myeloma. Significant results, which appear biologically plausible, were also obtained for rare nasal melanoma and mesothelioma. Although small samples sizes and multiple comparisons were of concern, many of the above associations were internally consistent and provide new diverse leads for discordant familial association of melanoma.

In plain English

This study used the Swedish Family-Cancer Database, which links about 15.7 million people into families with national cancer registry data up to 2012. It asked whether other cancers were more common in people whose parents or siblings had cutaneous (skin) melanoma, and the reverse. The authors calculated relative risks (RRs) adjusted for sex, age, calendar period, residential area and socioeconomic status. Only 8.57% of melanoma patients had a family history of melanoma. For combined pleural and peritoneal mesothelioma, the RR was 1.55 (95% CI 1.12 to 2.15, 51 cases) when one first-degree relative had melanoma. It was 2.14 (2 cases, 95% CI 0.43 to 10.75) when two relatives had melanoma, and the trend test was significant (p = 0.009). Neither pleural nor peritoneal mesothelioma was significant on its own, and most cases (36) were pleural. Breast, prostate, colorectal, skin and nervous system cancers also showed associations. The study did not examine asbestos exposure. The authors concluded that the mesothelioma link appeared biologically plausible and could reflect the BAP1-associated cancer syndrome. They noted concerns about small sample sizes and multiple comparisons in this exploratory study.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Nationwide registry-based family study comparing cancer incidence rates (familial relative risks) by family history, using Poisson regression adjusted for sex, age group, calendar period, residential area and socioeconomic status; described by the authors as exploratory
• Who was studied: Swedish Family-Cancer Database: 15.7 million individuals in families; analyses in the offspring generation (born from 1932 onwards, 8.5 million people, up to age 80), with cancers registered from 1958 through 2012; 38,102 melanomas in the offspring generation
• Exposure: Family history of cutaneous melanoma (single or multiple melanomas) in first-degree relatives (parents and/or siblings), and conversely family history of other cancers; no asbestos or occupational exposure data were studied
• Main results:
  • Only 8.57% of melanoma patients had a family history of melanoma
  • Melanoma risk rose with the number of affected relatives: RR 2.42 in 2-case families, up to 6.49 and 8.30
  • Combined pleural and peritoneal mesothelioma: RR 1.55 (51 cases, 95% CI 1.12 to 2.15) when one first-degree relative had melanoma
  • Combined mesothelioma: RR 2.14 (2 cases, 95% CI 0.43 to 10.75) when 2 first-degree relatives had melanoma; trend test significant (p = 0.009)
  • Neither pleural nor peritoneal mesothelioma was significant on its own; most cases (36) were pleural
  • In the reverse analysis, trend tests showed associations of melanoma with colorectal, breast, prostate, skin and nervous system cancer in relatives
• The authors' conclusion: The authors concluded that the association of melanoma with mesothelioma (and with nasal melanoma) appeared biologically plausible. They said the mesothelioma link could be expected as a manifestation of the BAP1-associated cancer syndrome.
• Limitations the authors state:
  • Exploratory study with concern about multiple comparisons
  • Small sample sizes
  • The two-way analysis compares cancers with different age distributions, which may reduce comparability
  • Few earlier independent studies exist and all are much smaller, so comparison with previous literature gives limited reassurance

Topics

Medical terms in this study, explained in our Lexicon: Genetic Counseling, Relative Risk, Myeloma, Mesothelioma.

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