Seven risk factors for early onset colorectal cancer in males identified

Reviewed by Danielle Ellis, B.Sc.Jun 27 2023

Colorectal cancer incidence and deaths are declining for individuals age 50 and older, but are increasing for those under 50.

A new study, led by researcher-clinician Thomas Imperiale, M.D., of the U.S. Department of Veterans Affairs, Regenstrief Institute and Indiana University School of Medicine, identifies seven risk factors for early onset colorectal cancer in males. The risk evaluation model the researchers developed may help 45- to 49-year-olds accept and adhere to new national screening recommendations and may also identify younger men for whom earlier screening should be considered.

"This study is important because it puts whether, and possibly how, to screen people who are younger than age 45 -- below the age for recommended colorectal cancer screening and have some of the risk factors we identify -- on the table for consideration for screening," said Dr. Imperiale.

"We know that colon cancer at younger ages is on the rise, although the absolute risk is still much lower than even in the 45- to 54-year-old age group. Nonetheless, that doesn't mean that we shouldn't be trying to identify younger people at higher risk to screen them with some modality," he said.

"Clinicians might have a discussion with a patient and say that although screening guidelines don't kick in until age 45 and you don't have a family history, you do have some risk factors. Might you consider a noninvasive screening test? It could be fecal occult blood testing or multi-target stool DNA testing. It doesn't have to be a colonoscopy. For men younger than 45 who are at higher-than-average risk, doing some type of screening would seem to make sense.

"When our study started it wasn't clear whether the same set of risk factors for older folks would apply to those who were getting cancer at younger ages," said Dr. Imperiale. "We found that while the weights assigned to some factors, such as family history and alcohol use, were about the same for men older and younger than 50, others, such as high body mass index (BMI) were risk factors for older but not younger men."

The study of 600 individuals with non-hereditary colon or rectal cancer plus 2,400 control patients from VA medical centers across the U.S., used electronic health record data and national VA datasets to determine sociodemographic and lifestyle factors, family and personal medical history, physical measures, vital signs, medications and laboratory values for six to 18 months. All participants were male veterans between the ages of 35 and 49. A total of 65 percent were White and 30 percent were Black.

Initially identifying 15 variables associated with early onset colorectal cancer, the researchers subsequently condensed the prediction model to seven factors that provide similar precision and would be easier to use in clinical practice to estimate relative risk.

The seven factors conveying higher-than-average risk for early onset colorectal cancer in males are:

• older age (within the 35- to 49-year-old age range)
• no regular use of non-steroidal anti-inflammatory drugs (such as aspirin or ibuprofen)
• no regular use of statins
• current alcohol use
• first or second degree relative with colorectal cancer
• a higher disease burden
• service-connection/copay variable – a marker for socio-economic status

We don't believe that any of these risk factors, with the exception of service-connection/copay variable, which we believe may be a proxy for income and/or socioeconomic status (and only an approximate one), are unique or specific to the veteran population."

Dr. Thomas Imperiale, M.D.

He is currently analyzing data on risk factors for early onset colorectal cancer in female veterans. The risk of colorectal cancer is twice as high for men as for women in any age category.

"Risk Factors for Early Onset Sporadic Colorectal Cancer in Male Veterans" is published in the peer-reviewed journal Cancer Prevention Research.

The study was funded by Health Services Research and Development, Veterans Health Administration (IIR 14-011) of the U.S. Department of Veterans Affairs.