Gene effect on colon cancer differs by gender

NEW YORK (Reuters Health) - Whether variant forms of a gene called EGFR increase or decrease survival with colon cancer depends on whether the patient is male or female, new study findings indicate.

Gender-related differences in colon cancer are recognized, including lower rates among women and gender-related response to treatment, according to the article in the journal Cancer Research. Expression of EGFR has been linked with a worse prognosis, but up until now, it was assumed that variants of the gene had a similar effect in men and women.

The research team at the Keck School of Medicine in Los Angeles, headed by Dr. Heinz-Josef Lenz, studied two variant forms of EGFR. One of the variants involved a change at a spot called codon 497 and the other involved a change in an area known as intron 1.

To examine the effects of the variants on survival, the researchers analyzed DNA from 318 patients with advanced colon cancer who had all received similar treatment.

When all 177 men and 141 women were considered, the EGFR variants did not influence survival. However, when men and women were analyzed separately, the variants affected survival differently.

Specifically, in men, the codon 497 variant decreased the usual survival period from 13.7 to 10.3 months. In women, however, the variant increased survival from 14.0 to 16.0 months.

The intron 1 variant also acted differently in men versus women. For the same genetic change, survival rose by 10.3 to 13.1 months in men, while it fell from 17.6 to 14.1 months in women.

As to mechanisms that might explain these differences, Lenz's group believes that it may relate to how the EGFR protein interacts with male and female hormone receptors in the colon.

These findings suggest, Lenz said in a statement, that gene variants "should be evaluated differently in women and men and that treatment decisions may depend on gender and not only on (genetic) or clinical findings."

SOURCE: Cancer Research, April 15, 2008.