Jun 2, 2009 - Research

Genetic Variations That May Affect Testicular Cancer Risk Identified

Variations in several genes may affect a young man’s risk of developing testicular cancer, new research says. One of these variations may also explain why the disease is more common in whites than blacks.

Testicular cancer is the most common type of cancer in men age 15 to 35, and it is on the rise.   The incidence of the disease in the United States has doubled since 1975.   The speed of this increase suggests that environmental factors are at work, but researchers know that genes have a substantial influence on the disease too — testicular cancer is one of the most heritable types of cancer.

Clear genetic risk factors for most cases of testicular cancer, however, have so far not been identified. But now two groups, publishing online this week in the journal Nature Genetics, report finding several common genetic variations that are associated with increased risk for the disease.

In a study of 730 men with testicular cancer and 1,435 controls, Rapley et al. found that each copy of the more common G version of a SNP in the KITLG gene increased the odds of testicular cancer by 2.55 times compared to two copies of the A version of this SNP. (The second study by Kanetsky et al. found a similar association with nearby SNPs in a similarly sized study).

Dr. Katherine Nathanson, an author of the Kanetsky et al. study, pointed out in a statement that the G version is very common in Caucasians.   This is noteworthy because it is usually the less common version of a SNP that is associated with increased disease risk.   In Nathanson’s opinion, men who carry two copies of the less common A version of the SNP are probably at “incredibly low risk” for testicular cancer.

In the same statement, lead author Peter Kanetsky suggested that the high prevalence of the riskier version of this SNPs might mean that it makes some men more susceptible to testicular cancer, but that some environmental factor may also be needed to actually cause disease.   He said that knowing which gene to look more closely at will help guide researchers’ efforts at identifying the other factors that are involved.

The KITLG gene has previously been associated with germ cell development and testicular cancer, but it is also involved in pigmentation.   Changes in this gene that are associated with lighter coloring have been strongly selected for in Europeans, and having a G at is one of the variations that is more common in whites than African Americans. The researchers suggest that this may be part of the reason the disease is almost five times more common in whites.

Rapley et al. also found that each copy of the A version of increased the odds of testicular cancer by 1.37 times compared to having two Gs (Kanetsky et al. also identified a similar association with a nearby SNP.) Each copy of a G at this SNP was found to increase the odds of testicular cancer by 1.50 times compared to having two As.

“These results raise the possibility that, in conjunction with other know risk factors, these variants may be used in the future for risk prediction, particularly given the availability of relatively simple screening approaches such as testicular ultrasound.   Further studies will be required, however, to refine the risk estimates and their interactions before this can be considered in clinical practice,” the authors of the Rapley et al. study conclude.

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