Family history of cancer and risk of paediatric and young adult's testicular cancer: A Norwegian cohort study

Our plain-English summary of Family history of cancer and risk of paediatric and young adult's testicular cancer: A Norwegian cohort study, by R. Del Risco Kollerud, E. Ruud, H.S. Haugnes, et al (British Journal of Cancer, 2019).

The study

• Authors: R. Del Risco Kollerud, E. Ruud, H.S. Haugnes, L.A. Cannon-Albright, M. Thoresen, P. Nafstad, L. Vlatkovic, K.G. Blaasaas, Ø. Næss, B. Claussen
• Journal: British Journal of Cancer
• Published: 2019;120(10):1007-1014
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The aim of this study was to examine the association of a family history of cancer with the risk of testicular cancer in young adults.

Methods: This is a prospective cohort study including 1,974,287 males born 1951-2015, of whom 2686 were diagnosed with TC before the age of 30.

Results: A history of TC in male relatives was significantly associated with a diagnosis of TC among children and young adults, including brothers (6.3-fold), sons (4.7-fold), fathers (4.4-fold), paternal uncles (2.0-fold) and maternal uncles (1.9-fold). Individuals with a father diagnosed with a carcinoma or sarcoma showed an elevated risk (1.1-fold and 1.8-fold, respectively). A family history of mesothelioma was positively associated with a risk of TC [(father (2.8-fold), mother (4.6-fold) and maternal uncles and aunt (4.4-fold)]. Elevated risks were also observed when siblings were diagnosed with malignant melanoma (1.4-fold). The risk of TC was also increased when fathers (11.1-fold), paternal (4.9-fold) and maternal uncles and aunts (4.6-fold) were diagnosed with malignant neuroepithelial-tumours.

Conclusion: We found an increased risk of TC among children and young adults with a family history of TC, carcinoma, mesothelioma, sarcoma, malignant melanoma and malignant neuroepithelial tumours. Hereditary cancer syndromes might underlie some of the associations reported in this study.

In plain English

This Norwegian registry-based cohort study followed all 1,974,287 males born in Norway from 1951 to 2015. Of these, 2686 were diagnosed with testicular cancer before age 30. The authors compared testicular cancer risk according to cancers diagnosed in parents, siblings, uncles and aunts; sons appeared only in the comparison of testicular cancer in relatives. Mesothelioma in a relative was associated with higher risk: hazard ratios were 2.77 (95% CI 1.38 to 5.56) for an affected father, 4.62 (1.16 to 18.50) for an affected mother, and 4.44 (1.85 to 10.70) for affected maternal uncles or aunts. These figures rested on 8, 2 and 5 affected cases. The article reported no measurement of asbestos or other environmental exposures. Testicular cancer in male relatives was associated with raised risk, including a hazard ratio of 6.26 (4.97 to 7.89) for an affected brother. Carcinomas, sarcomas, malignant melanoma and malignant neuroepithelial tumours in some relatives were also linked to raised risk. The authors suggested hereditary cancer syndromes, such as BAP1 tumour predisposition syndrome, might explain some associations. They noted that shared environmental factors could not be excluded, that the mesothelioma results rested on small numbers, and that the study was hypothesis generating.

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: Population-based (registry-linked) prospective cohort study using Cox proportional hazard regression
• Who was studied: All 1,974,287 males born in Norway from 1951 to 2015 were followed from birth to age 30, death, emigration or end of study. Of these, 2686 were diagnosed with testicular cancer before age 30. Their parents, siblings, uncles and aunts were identified through the Central Population Register and linked to the Norwegian Cancer Registry. Offspring were excluded from the broader analyses, but sons appeared in the testicular cancer comparison.
• Exposure: Family history of cancer, grouped by cancer type (including mesothelioma) and by organ of origin in relatives. The article reports no measurement of asbestos or other environmental exposure. Models were adjusted for birth year, number of relatives, and the mother's or father's education.
• Main results:
  • Mesothelioma in relatives was associated with testicular cancer risk. Hazard ratios were 2.77 (95% CI 1.38 to 5.56) for an affected father, 4.62 (1.16 to 18.50) for an affected mother, and 4.44 (1.85 to 10.70) for affected maternal uncles and aunts. These were based on 8, 2 and 5 cases with an affected relative. Estimates were not calculated for siblings or for the father's siblings.
  • Testicular cancer in male relatives was associated with testicular cancer risk. Hazard ratios were 6.26 (4.97 to 7.89) for a brother, 4.70 (2.34 to 9.42) for a son, 4.37 (3.13 to 6.10) for a father, 2.04 (1.23 to 3.40) for a father's brother, and 1.88 (1.15 to 3.08) for a mother's brother.
  • Carcinoma was associated with testicular cancer risk when it occurred in fathers (HR 1.11, 1.00 to 1.23) and in maternal uncles and aunts (HR 1.15, 1.02 to 1.30). Sarcoma in fathers had an HR of 1.81 (1.10 to 2.96).
  • Malignant melanoma in siblings had an HR of 1.45 (1.01 to 2.06).
  • Malignant neuroepithelial tumours had HRs of 11.15 (2.78 to 44.57) in fathers, 4.92 (1.23 to 19.70) in paternal uncles and aunts, and 4.62 (1.15 to 18.50) in maternal uncles and aunts. Each estimate rested on 2 cases.
• The authors' conclusion: The authors concluded that risks of testicular cancer were raised in children and young adults with a family history of testicular cancer, carcinomas, mesothelioma, sarcomas, malignant melanoma and malignant neuroepithelial tumours. They suggested hereditary cancer syndromes, such as BAP1 tumour predisposition syndrome, could be involved in a predisposition to testicular cancer in young males. They said results must be interpreted with caution.
• Limitations the authors state:
  • The mesothelioma analyses were based on a small number of cases.
  • The authors said their findings did not exclude a possible influence of shared environmental factors among family members.
  • The study was registry-based, with no biological samples available for genetic analysis.
  • Some associations rested on small numbers and could be false positives.
  • Cancer follow-up of relatives ended in 2015, and many relatives were young. The authors said this would tend to underestimate risk.
  • Offspring of the index persons had too few cancer cases to be included in the broader analyses.
  • The population was primarily white, so the findings may not apply to other populations.
  • The authors described the study as hypothesis generating because many hypotheses were tested.

Topics

Medical terms in this study, explained in our Lexicon: Cohort Study, Carcinoma, Sarcoma, Mesothelioma.

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