Colorectal Cancer Causes

by National Cancer Institute

(Page 3 of 3)

Cigarette use is a risk factor for developing colorectal adenomas. Inherited variation in two genes (NQO1 and CYP1A1), which influence the activation of the cancer-causing substances in tobacco smoke, were found to increase risk for developing colorectal adenomas.

In this study, researchers investigated the roles of variations in the CYP1A1 and NQ01 genes, combined with tobacco use, on the development of colorectal adenomas. These genes play a role in activating the cancer-causing substances in tobacco smoke. While tobacco use has been found to be a risk factor for developing colorectal adenomas, the role of these two genes is unclear. For this study, 772 people with at least one advanced adenoma and 777 people with no adenomas completed questionnaires about their lifestyles and had genetic tests done on their blood to determine if they had changes in these two genes.

The researchers found that the risk of having advanced colorectal adenomas was increased in smokers who had a variation in either the CYP1A1 gene or the NQO1 gene, and greatest in those with variations in both genes. In people who did not smoke, these gene variations did not affect their risk for developing colorectal adenomas.

Microsomal epoxide hydrolase (EPHX1) is responsible for breaking down carcinogens in cigarette smoke. Variations in this gene that increase EPHX1 protein activity appeared to increase risk for colorectal adenoma, particularly among recent and current smokers.

Microsomal epoxide hydrolase (EPHX1) is a protein that breaks down polycyclic aromatic hydrocarbons found in cigarette smoke, which are known to cause cancer. However, in the process of breaking down these carcinogens, EPHX1 creates another carcinogen, benzo(a)pyrene 7,8 dihydrodiol 9,10 epoxide (BPDE).

Researchers looked at two variations in the EPHX1 gene that are thought to affect the level of activity of the EPHX1 protein. They compared 772 people with advanced colorectal adenoma to 777 people without the disease. Detailed information on smoking history was collected from a risk factor questionnaire that participants filled out when they enrolled in the PLCO study. Non-smokers were considered those who did not smoke cigarettes for more than six months or who did not smoke pipes or cigars for more than one year. Current or recent smokers were those who quit less than 10 years before enrollment in the study.

Researchers found that those participants with variations in the EPHX1 gene, which led to higher protein activity, had an increased risk of colorectal adenoma. This was especially true among recent and current smokers.

Even though iron has been suggested as a risk factor for colorectal cancer, there was no relationship found between dietary intake of iron and risk of colorectal adenomas, the precursor condition to colorectal cancer. In addition, genetic variations that increase levels of iron in the blood were not found to be related to adenoma risk.

Both iron intake and measures of iron in the blood have been suggested to be related to increases in the risk of colorectal cancer and adenoma. Researchers looked at iron intake and genetic variation in 679 people with advanced colorectal adenoma and 697 controls. Iron intake information was taken from participant responses to a food frequency questionnaire. Researchers found no relationship between iron intake and risk of adenoma.

Variations in the hemochromatosis gene (HFE) affects levels of iron in the blood. Researchers who looked at three different polymorphisms, or variations in this gene, did not find any relationship between the polymorphisms and risk of adenoma.

People who had a high calcium intake, greater than 1200 mg/d (milligrams per day), had reduced risk of colorectal adenoma, a pre-cursor condition to cancer.

Calcium can reduce the risk of colorectal tumors by reducing exposure to harmful compounds in the bowel, or by influencing various cellular activities in the colon, such as cell growth and death. This study compared supplemental and dietary calcium intake of 3,696 people with adenoma to 34,817 controls. Calcium intake information was derived from individual responses on a food frequency questionnaire. Researchers found that people with the highest intakes of calcium had the lowest risk of colorectal adenoma. The association between intake and risk was stronger for calcium from nondairy foods and supplements, and for adenoma of the distal colon, the part of the colon farthest from the stomach.

Variations in the calcium-sensing receptor gene were associated with advanced colorectal adenoma, a precursor condition to cancer. Also, a protective association was found between total calcium intake and advanced colorectal adenoma risk.

The calcium-sensing receptor (CASR) is thought to mediate calcium's role in preventing cancer. Researchers looked at three common polymorphisms, or variations, in this gene in 772 people with advanced colorectal adenoma and 777 people without the disease. They found an association between advanced colorectal adenoma and these polymorphisms. This is the first study to evaluate variations in this gene in relation to risk of colorectal adenoma. Therefore, this study contributes new data that show a mediating role of CASR in preventing cancer.

This study also looked at calcium intake by reviewing participants' answers to a food frequency questionnaire which contained questions about dietary calcium intake and supplement use. A protective association was found for total calcium intake. For each additional 1,000 mg of calcium they took, participants had a 21 percent reduction in risk of advanced colorectal adenoma.

The VDR TaqI variation in the vitamin D receptor gene was not associated with risk of advanced colorectal adenoma, a pre-cursor condition to cancer. One vitamin D metabolite, 1,25(OH)2D, was not associated with advanced adenoma risk. Another vitamin D metabolite, 25(OH)D, was inversely associated with advanced adenoma risk in women but not in men.

Vitamin D may be involved in the prevention of colorectal cancer, and this action may be mediated by the vitamin D receptor (VDR). Researchers analyzed a polymorphism, or variation in the VDR gene, called VDR TaqI, in 763 people with advanced colorectal adenoma and 774 people without the disease. They found no association between this polymorphism and adenoma.

Researchers also measured blood serum levels of two vitamin D metabolites, 1,25(OH)2D and 25(OH)D, in a subset of 394 cases and 397 controls. They found that serum levels of 1,25(OH)2D were not associated with adenoma risk. However, for the second metabolite, 25(OH)D, researchers found that higher levels were associated with a decreased adenoma risk in women, but not in men. In women, when comparing those in the highest quintile with those in the lowest quintile, the risk of advanced adenoma decreased by 73 percent.

People who had a high level of fiber in their diet were at lower risk of colorectal adenoma, a pre-cursor condition to cancer.

The potential impact of dietary fiber on colorectal cancer risk is controversial. Researchers examined fiber intake from food and supplements in 3,591 people with adenoma, and 33,971 people without the disease. They found that risk of adenoma decreased with increasing intake of dietary fiber in both men and women. People in the highest quintile of fiber intake, who consumed approximately 24 more grams of fiber per day than those people in the lowest quintile, had a 27 percent decrease in adenoma risk compared with those in the lowest quintile.

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