Metabolic syndrome and obesity are positively linked with colorectal cancer before age 50, with rates similar to those in people diagnosed with CRC after age 50, reports a new study by Eun Hyo Jin, PhD, with the Department of Internal Medicine, Seoul National University College of Medicine, in Seoul, Korea, and colleagues.
The rates may be similar, but the cancers seem to be different.
Metabolic syndrome was significantly associated with increased risk for earlier-onset CRC, particularly in the distal (left-sided) colon and rectum — locations previously associated with earlier-onset CRC — but not the proximal (right) colon, the site of about half of all CRC cases in people aged 65 years or older.
The results were published online in Gastroenterology.
Rise in Earlier-Onset Colorectal Cancer
The overall incidence of CRC and mortality have decreased gradually in patients aged 50 years or older, with more screening and improvements in treatments and modifiable risk factors.
But for those younger than 50, CRC has been on the rise globally since the mid-1990s.
All racial groups share an increasing trend of earlier-onset CRC, the authors write, but the rapid increase in South Korea recently led to the highest rate among 42 countries, according to cancer registry data.
The prevalence of metabolic syndrome has also increased significantly in the under-40 age group, the authors note, from 16.2% in 2011 to 21.3% in 2016. Metabolic syndrome comprises a number of conditions, including abdominal obesity, hyperglycemia, raised blood pressure, elevated triglycerides, and low HDL-C.
Because obesity and metabolic syndrome are linked to CRC in older adults, the researchers wanted to know whether the same association exists for earlier-onset CRC.
They conducted a retrospective nationwide study of de-identified data on 9,774,081 people who got health checkups through the Korean National Health Insurance Service from 2009 to 2010 and were followed through 2019. During the decade of follow-up, 8320 earlier-onset and 57,257 later-onset CRC cases developed.
Researcher analyzed laboratory data and data on age, sex, lifestyle factors, body mass index (BMI), waist circumference (WC), and blood pressure. They performed a multivariate Cox proportional hazards regression analysis.
Metabolic syndrome was linked with increased earlier-onset CRC (adjusted hazard ratio (aHR), 1.20; 95% CI, 1.14-1.27). Researchers adjusted for sex, age, smoking, alcohol use, regular exercise, and income. They found a similar link with later-onset CRC (aHR, 1.19; 95% CI, 1.17-1.21).
“Our study showed that of the metabolic syndrome components, abdominal obesity was the strongest single risk factor associated with earlier-onset CRC (HR 1.23; 95% CI: 1.16-1.30),” the study authors write.
Metabolic syndrome was also significantly associated with increased risk for earlier-onset CRC across particular tumor locations, the researchers found.
“We found that a higher BMI/WC was significantly associated with increased earlier-onset CRC. These dose-response associations were significant in distal colon and rectal cancers, though not for proximal colon cancer.”
Other studies have reported distinct molecular features of earlier-onset CRC that may explain variation in locations and pathogenic mechanisms, the authors note.
Personalizing CRC Screening
Andres Acosta, MD, PhD, an obesity expert at the Mayo Clinic in Rochester, Minnesota, points out that in 2021, the recommended age for CRC screening dropped from 50 years to 45 years.
“Despite that, we still see there are patients who remain at high risk even in younger populations,” he told Medscape Medical News. “Young people with obesity fall into that group.”
Although there is no talk currently of lowering that age even further for screening overall, Acosta said studies like this one help make the case for a more personalized approach for who should be targeted for screening earlier.
“Hopefully, in the future we can move to guidelines that don’t just use age as a cutoff but start using other factors, such as obesity, to start early screening,” said Acosta, who was not involved in the study.
Strengths of the study, Acosta said, include the large sample size and the methodology that used adjusted risk factors. He said the findings from the Korean population support what has been found in other populations as well.
ore Testing Earlier May Be Low Impact
Otis Brawley, MD, Bloomberg Distinguished Professor of Oncology and Epidemiology at the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, told Medscape Medical News that the information in the study is important but said that people with metabolic syndrome are at far higher risk for cardiovascular disease and stroke and other cancers than they are for colorectal cancer.
“While this is something to take into account, if we’re going to be holistic, we have to realize those other things are a much higher risk,” he said.
The paper does help prioritize preventing obesity in the first place, he said.
Screening for CRC at age 45 years should be encouraged, he said, “but if you really want to save lives, you should get to the 40% of people in their 60s who are not getting [CRC screening].”
Brawley said many more cumulative life-years will be saved by getting to that 40% of people in their 60s who are not getting screened than by screening people in their 40s.
He noted that adding CRC screening in younger years for people with metabolic syndrome sounds positive, but “if you start burning resources for low-impact things, you deprive people who need those resources.”
The authors and Acosta report no relevant financial relationships. Brawley has done consulting for Grail, which is developing a blood test that includes CRC screening.
Gastroenterology. Published online May 25, 2022. Abstract
Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and Nurse.com, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St.Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick