A history of cancer at an early age still tops familial links to concordant cancers, but some cancers have familial links that extend into diagnosis at advanced ages, investigators reported.

The highest familial risk occurred in people who had diagnoses at an early age and whose parents had diagnoses of the same type of cancer at an early age, reported Elham Kharazmi, MD, PhD, of the German Cancer Research Center in Heidelberg, and colleagues in BMJ.

For some types of cancer, the excess risk conferred by family history extended to cancers diagnosed in parents at ages 90 and older, including skin squamous-cell carcinoma (90% excess risk), colorectal cancer (60%), breast cancer (30%), and prostate cancer (30%).

“Our study suggests that the bulk of familial cancers of advanced ages are included in the moderate-risk category, which does demand increased clinical surveillance and further investigations to identify factors that affect cancer susceptibility at advanced ages,” the group wrote.

“Finding the causes of even modest proportion of familial aggregation of a disease could be a major step toward understanding the causes of the disease itself,” they added. “As cancer diagnosis even in a very old parent can be a predictor of higher risk of the same cancer in their offspring, offspring might benefit from knowing this risk by avoiding known modifiable risks factors for that particular cancer.”

Older age is associated with an increased risk of most types of cancer. As populations continue to age, cancer diagnoses in older individuals are expected to increase.

Early-onset cancer increases the risk of cancer in offspring, as compared with cancers that arise later in life. Whether cancers of older age have a familial component has received scant attention in the medical literature, providing a rationale for the investigation by Kharazmi and colleagues.

They queried the national Swedish databases to identify all Swedes born after 1931, as well as their biological parents, resulting in a study population of more than 12.2 million people. The search also revealed more than 1.1 million new primary cancer diagnoses.

The primary objective of the study was to determine familial risk of concordant cancers (parents and offspring with the same type cancer) by age at diagnosis. Because they wanted to examine familial cancer risk in advanced age, investigators limited results to cancer site with at least 50 cases in the offspring of parents whose cancer was diagnosed at age 80 and older.

Overall, 35% to 81% of familial cancers in parents were diagnosed after age 69, including 59% of colorectal cancers, 56% of lung cancers, 75% of prostate cancers, 62% of bladder cancers, 81% of nonmelanoma skin cancer, and 54% of cases of non-Hodgkin lymphoma.

Consistent with previous reports, the results showed the highest risk associated with diagnosis of parental cancers at a younger age.

For example, colorectal cancer diagnosed before age 60 combined with parents whose colorectal cancer was diagnosed before age 40 produced a hazard ratio of 9.9. If the parents’ cancers were diagnosed at ages 80 to 90, the HR declined to 1.7, although it remained significant.

When parents were diagnosed at age 90 and up, the risk of concordant cancer in offspring was still significantly increased for:

  Skin squamous cell carcinoma (HR 1.9, 95% CI 1.4 to 2.7)
  Colorectal cancer (HR 1.6, 95% CI 1.2 to 2.0)
  Breast cancer (HR 1.3, 95% CI 1.0 to 1.6)
  Prostate cancer (HR 1.3, 95% CI 1.1 to 1.6)

The relative risk of concordant cancer in offspring remained significantly increased for all of those diseases, along with lung and bladder cancer, melanoma, and non-Hodgkin lymphoma when parents’ cancers were diagnosed at ages 70 to 79 or 80 to 89. The magnitude of the risk in offspring ranged from 1.3 to 2.7, depending on the type of cancer, parents’ age at diagnosis, and offspring’s age at diagnosis.

The study had some limitations. It’s possible that some elderly people in the database underwent less screening and medical surveillance rather than experiencing a truly decreased disease risk. Also, environmental and lifestyle risk factors may differ between younger and older people, the authors said.

They called for additional studies with more information on residual confounders such as obesity, alcohol consumption, and smoking.

The study was supported by the Swedish Council for Working Life and the German Cancer Aid.

The authors reported no conflicts of interest.

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Primary source: BMJ
Source reference: Kharazmi E, et al “Familial risk of early- and late-onset cancer: Nationwide prospective cohort study” BMJ 2012; DOI: 10.1136/bmj.e8076.