University of Illinois scientists have evidence that lifelong exposure to genistein, a bioactive component in soy foods, protects against colon cancer by repressing a signal that leads to accelerated growth of cells, polyps, and eventually malignant tumors.
“In our study, we report a change in the expression of three genes that control an important signaling pathway,” said Hong Chen, a U of I professor of food science and human nutrition.
The cells in the lining of the human gut turn over and are completely replaced weekly, she noted. “However, in 90 percent of colon cancer patients, an important growth-promoting signal is always on, leading to uncontrolled growth and malignancies. Our study suggests that the aberrant Wnt signaling during the development of colon cancer can be regulated by soy-rich diets.”
“The good news is that a diet rich in soy genistein represses those signals through epigenetic modifications at the regulatory regions of those genes,” said Yukun Zhang, a doctoral student in Chen’s laboratory.
Chronic exposure to genistein, a soy isoflavone, reduced the number of pre-cancerous lesions in the colons of laboratory rats exposed to a carcinogen by 40 percent and reduced Wnt signaling to normal levels, she said.
In their study, the scientists modeled lifetime exposure to soy by feeding pregnant rats and their offspring a diet containing soy protein isolate and a diet that contained genistein compound. At seven weeks of age, offspring rats were exposed to a carcinogen, and they continued eating either the soy protein or the genistein diet until they were 13 weeks old.
At that time, the researchers inspected the colons of rats in both soy groups and compared them to rats in a control group, noting the number and severity of tiny abnormal growths in each. They also compared Wnt signaling before and after the carcinogen to see whether either diet had any effect on its upregulation.
In the genistein-fed animals, signaling levels were similar to rats that had not received the carcinogen.
“Genistein decreased the expression of three genes and repressed this signaling process that is associated with abnormal cell growth and cancer development,” Chen said.
The relationship of the intake of soy products and the incidence of colon cancer was prospectively evaluated in a population-based cohort study in Japan. The total intake of soy products and isoflavones in a daily diet was estimated from a validated questionnaire administered at the baseline. The participation rate of the questionnaire was 92.0%. The participants were followed from 1992 to 2000, and colon cancer diagnoses were identified at the main hospitals in the study area. In the analysis, 13,894 men and 16,327 women were included. The medians for energy-adjusted soy product intake were 85.52 g/day for men and 79.60 g/day for women. During follow-up, 111 men and 102 women were diagnosed with colon cancer. A Cox-proportional hazard model was applied to assess the risk of colon cancer incidence. Among women, the risk was reduced with an increased soy product consumption; the hazard ratio in the highest tertile was 0.56 (95% CI 0.34-0.92) compared as the lowest tertile (trend: P=0.04), after adjusting for multiple potential confounders. Among men, no significant association was observed. Our results exhibited the weak benefit of soy foods only among women.
Oba S, Nagata C, Shimizu N, Shimizu H, Kametani M, Takeyama N, Ohnuma T, Matsushita S.
She said this shows that colon cancer is an epigenetic disease, meaning that dietary and environmental factors can influence genes to be switched on or off so you have a different pattern of gene expression, leading to a change in disease susceptibility.
It has long been known that immigrants from Asia - where soy is traditionally a food staple - experience rising levels of colon cancer as they adopt the eating habits of the Western nations they now call home, she said.
“The genetic information you inherit from your parents is not the whole story. Our dietary choices, our exposure to environmental toxins, even our stress levels, affect the expression of those genes,” she said.
DNA methylation and histone modification of Wnt genes by genistein during colon cancer development will appear in an upcoming issue of Carcinogenesis and is available pre-publication online at carcin.oxfordjournals.org/content/early/2013/05/22/carcin.bgt129.abstract?sid=2c12c8c0-8bdc-43f3-9313-9c0e812b9256
Yukun Zhang, Qian Li, and Hong Chen, all of the U of I, are co-authors. The study was funded by the National Institutes of Health, U of I Research Board, and the Illinois Soybean Association.
Soy consumption and colorectal cancer.
Spector D, Anthony M, Alexander D, Arab L.
Source: School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
We explored the postulated association between soy foods and colorectal cancer incidence by analyzing 13 epidemiological studies: 3 ecological, 1 cohort, and 9 case control. Seven case-control studies evaluated the association between soy intake and colon or colorectal cancer (2,008 cases). Point estimates generally suggest an inverse association between higher soy consumption and colon cancer onset, although nearly all of the confidence intervals overlap 1.0. Two of the nine case-control studies focused on adenomas as the outcome (675 total cases), and results for these studies also showed inverse associations. Of the six case-control studies that evaluated the association between soy consumption and rectal cancer (732 cases), the point estimates generally suggest an inverse association with unfermented soy consumption and rectal cancer onset but not fermented soy products. These studies have many limitations, particularly with regard to dietary measurement issues, such as incomplete assessment of soy intake, inadequate quantification, and inappropriate time period for cancer prevention as well as inadequate adjustment for confounders. Most of these issues would contribute to underestimations of any association. In spite of the methodological issues, the available evidence is compelling enough to warrant further study utilizing stronger methodology.
University of Illinois College of Agricultural, Consumer and Environmental Sciences