Functional polymorphisms in the gene expressing epidermal growth factor receptor (EGFR) have opposite prognostic implications for male and female patients with metastatic colon cancer, new study findings indicate.

Gender-related differences in colon cancer are recognized, according to the article in the April 15 issue of Cancer Research, including lower incidence among women and sex-related treatment responses. However, EGFR is widely expressed in colonic tissues, and up until now, the worse prognosis indicated by EGFR activation has been considered gender neutral.

The research team at the Keck School of Medicine in Los Angeles, headed by Dr. Heinz-Josef Lenz, studied two independent functional polymorphisms of EGFR, one at codon 497 in the extracellular domain of the EGFR gene and the other related to dinucleotide repeats within intron one.

To examine the effects of the variants on survival, the researchers analyzed genomic DNA from 318 patients with metastatic colon cancer who had undergone similar treatment.

In the combined cohort of 177 men and 141 women, the EGFR polymorphisms were not associated with survival, results showed. However, when men and women were analyzed separately, the EGFR gene variants affected survival differently.

Specifically, median overall survival in men with the arg/arg variant of the 497 polymorphism was 10.3 months while for those with a lys allele it was 13.7 months. Among women, the corresponding figures were 16.0 months and 14.0 months.

For the intron polymorphism, repeat length < 20 in men was associated with a median overall survival of 10.3 months compared with 13.1 months with repeat length > 20. The corresponding survival rates for women were 17.6 and 14.1 months.

The gender-related survival differences in both cases are novel, the scientists note.

As to mechanisms that might explain these differences, Dr. Lenz's group points out that the colon expresses both estrogen receptor beta and androgen receptor, and that EGFR interacts with both. Therefore, "EGFR may have molecular intermediates that interact in a gender-specific way to effect EGFR pathway activation."

These findings suggest, Dr. Lenz said in a statement, that "molecular markers should be evaluated differently in women and men and that treatment decisions may depend on gender and not only on molecular or clinical findings."


Cancer Res 2008;68:3037-3042