Gender Impacts Colorectal Cancer Progression

"Taking gender into account when examining the genetic profile of patients may help to those who will benefit from specific chemotherapy treatments," says principal investigator Heinz-Josef Lenz, M.D., professor of medicine at USC's Keck School of Medicine.

Findings from the study were displayed on Monday, June 4 at the annual meeting of the American Society of Clinical Oncology (ASCO) held at McCormick Place in Chicago.

The study focused specifically on patients who had been treated with 5-Fluorouracil and oxaliplatin chemotherapy, Lenz says. Researchers were able to identify molecular markers predicting response time to tumor progression and overall survival.

"When we stratified for men and women, different genes appear to be predictive for outcome," says Lenz. "This is the very first study showing that molecular markers may be sex specific."

There has been increasing evidence that gender plays a significant role in the development and progression of colorectal cancer, Lenz explains. Colorectal cancer rates are higher among men, and previous studies have shown a protective effect of female hormones.

Seventy-four female and 78 male patients participated in the study, which analyzed 24 polymorphisms in 12 genes involved in cancer progression. Researchers tested for association of specific polymorphisms with overall survival (OS), time to tumor progression (TTP) and tumor response.

Men carrying polymorphisms in the ER-ß and SCN1A genes had improved TTP, versus women carrying polymorphisms in the XPD and EGFR genes. Likewise, male patients carrying ER-ß and MTHFR polymorphisms had improved overall survival, while female patients carrying polymorphisms in SCN1A and PLA2 genes had improved OS.

"These findings are critical since men and women are usually not divided when molecular research is being done," Lenz explains. "Our results suggest for the first time that genomic profiling to predict clinical outcome of patients with metastatic colorectal cancer depends on gender."

Funding for this study come from the San Pedro Guild and Cornelius Pings Memorial Fund.

Michael A. Gordon, Wu Zhang, Dongyun Yang, Fumio Nagashima, Hueng-Moon Chang, Georg Lurje, Eva Borucka and Heinz-Josef Lenz, "Sex-specific genomic profile predicts clinical outcome in metastatic colorectal (mCRC) patients treated with 5-Fluorouracil/Oxaliplatin." Presented at 8 a.m., Monday June 4, 2007.