TOP LIST OF HEREDITARY CANCER

BOSTON — One legacy that most men could do without is an inherited risk for prostate cancer, but a massive cohort study shows that for some men, genetic history hints at oncologic destiny.

Data on both identical (monozygotic) and fraternal (dizygotic) twins from the comprehensive birth-to-death registries in Denmark, Finland, Norway, and Sweden show that a man whose monozygotic twin has prostate cancer has a 32% risk for the disease himself, whereas a dizygotic twin whose brother has prostate cancer has only a 16% risk, said Jaakko Kaprio, MD, PhD, professor of genetic epidemiology at the University of Helsinki.

The estimated heritability of prostate cancer — the degree to which genes contribute to risk — was 58% (95% confidence interval, 52 - 63), which is the highest for any malignancy studied, Dr. Kaprio reported here at the American Society of Human Genetics 63rd Annual Meeting.

"These estimates for common cancers are greater than previously estimated. For rare cancers, such as testicular cancer, the concordance risk was substantial. We believe it provides an accurate estimate of familial risk prediction," Dr. Kaprio told Medscape Medical News.

Table. Cancers With Significant Heritability

Cancer Type	Heritability Estimate, %	95% Confidence Interval
Prostate	58	52–63
Testicular	36	2–95
Breast	28	12–52
Kidney	23	11–42
Lung	25	12–44
Melanoma	39	8–81
Ovarian	28	15–47
Stomach	24	5–65
Uterine	24	14–87
Colon	16	2–63

The magnitude of the genetic contribution to prostate cancer found in this study is higher than the estimated 42% seen in a previous study of Nordic twins (N Engl J Med. 2000;343:78-85). Dr. Kaprio explained that this difference can be attributed to the fact that his team expanded the original cohort to include data from Norway, had 10 additional years of follow-up data, and had an aging cohort, with a resultant increase in incident cancers.

Dr. Kaprio's team looked at data on 133,689 monozygotic and dizygotic pairs as part of the Nordic Twin Registry of Cancer. They used time-to-event analysis to estimate heritability and familial cancer risk.

What's Going On?

This study raises important questions about the interplay between genetics and environment in cancer, said Richard Stevens, PhD, professor of cancer epidemiology at the University of Connecticut Health Center in Farmington.

"It's a very strong study. The exciting thing about this study with prostate cancer is that it's certainly saying something about mechanism that we don't get," he explained.

The study supports the presence of genetic polymorphisms in prostate cancer, and to a lesser degree breast cancer, that can cumulatively contribute to risk, he said.

"The specific polymorphisms we're aware of — familial syndromes — account for very little breast cancer or prostate cancer. There are other genes where allelic variation and risk is moderate. There must be a lot of those genes with moderate risk; you put them together and it makes you more susceptible," Dr. Stevens said.

The study was supported by the Ellison Foundation and the Nordic Cancer Union. The study authors and Dr. Stevens have disclosed no relevant financial relationships.

American Society of Human Genetics (ASHG) 63rd Annual Meeting: Abstract 43. Presented October 23, 2013.