Study Identifies Potential Risk Factors for Early-Onset Colorectal Cancer in Male Patients

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Researchers have identified seven potential risk factors for early-onset colorectal cancer in male patients and developed a novel risk evaluation model, according to a recent study published by Imperiale et al in Cancer Prevention Research. The findings may help 45- to 49-year-old patients accept and adhere to the recent national screening recommendations and may also identify younger male patients who should undergo earlier screenings.


The incidence and mortality of colorectal cancer are declining for patients older than 50 but are increasing for those younger than 50. In previous studies, investigators have found that the risk of colorectal cancer may be twice as high for male patients as it is for female patients in any age group.

“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 [patients] at higher risk to screen them with some modality,” explained lead study author Thomas Imperiale, MD, the Lawrence Lumeng Professor of Gastroenterology and Hepatology as well as the Distinguished Professor of Medicine in the Division of Hematology/Oncology at the Indiana University School of Medicine, a research scientist at the William M. Tierney Center for Health Services Research at the Regenstrief Institute, and a core investigator at the U.S. Department of Veterans Affairs (VA) Health Services Research and Development Center for Health Information and Communication at the Richard L. Roudebush Veteran’s Administration Medical Center. “When our study started, it wasn’t clear whether the same set of risk factors for older [patients] would apply to [younger patients]. We found that while the weights assigned to some factors—such as family history and alcohol use—were about the same for [male patients of all ages], others such as high body mass index were risk factors for older but not younger [male patients],” he added.

Study Methods and Results

In the recent study, the researchers analyzed the sociodemographic and lifestyle factors, family and personal medical histories, physical measures, vital signs, medications, and laboratory values of 600 patients with nonhereditary colorectal cancer and 2,400 control patients from VA medical centers across the United States using electronic health records and national VA data sets for 6 to 18 months. All the patients who participated in the study were male veterans between the ages of 35 and 49. Further, 65% of them identified as White, and 30% identified as Black.

The researchers initially identified 15 variables associated with early-onset colorectal cancer, but subsequently they condensed the prediction model to 7 factors that provided 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 male patients follow:

  • Older age: patients between the ages of 35 and 49
  • Lack of regular nonsteroidal anti-inflammatory drug use such as aspirin or ibuprofen
  • Lack of regular statin use
  • Current alcohol use
  • First- or second-degree relatives with colorectal cancer
  • Higher disease burden
  • Service-connection/copay variable as a marker for socioeconomic 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. Imperiale noted.


“Clinicians might have a discussion with a patient and say, ‘Although screening guidelines don’t kick in until age 45, and you don't have a family history [of colorectal cancer], you do have some risk factors. [Y]ou [might want to] consider a noninvasive screening test. It could be fecal occult blood testing or multitarget stool DNA testing. It doesn’t have to be a colonoscopy.’ For [male patients] younger than 45 who are at higher-than-average risk, doing some type of screening would seem to make sense,” Dr. Imperiale underscored. “This study is important because it puts whether, and possibly how, to screen [patients] who are younger than age 45—and have some of the risk factors we identify—on the table for consideration,” he concluded.

The researchers are currently analyzing data on risk factors for early-onset colorectal cancer in female veterans.

Disclosure: The research in this study was funded by Health Services Research and Development at the Veterans Health Administration at the U.S. Department of Veterans Affairs. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.