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Obesity may increase risk for colorectal cancer among women

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October 11, 2018

Women with a BMI of 30 kg/m2 or greater demonstrated an increased risk for early-onset colorectal cancer, according to data from the ongoing prospective Nurses’ Health Study II.

“In contrast to the decreasing trends in adults 50 years or older, incidence and mortality of colorectal cancer have been increasing among all age groups between 20 and 49 years,”

Po-Hong Liu, MD, MPH, researcher at Massachusetts General Hospital and Harvard Medical School, and colleagues wrote. “The drivers for the increases in incidence of early-onset colorectal cancer have not been elucidated. Increasing prevalence of established colorectal cancer risk factors, such as obesity, sedentary lifestyle, Western diet and diabetes, may contribute.”

Liu and colleagues used data from the Nurses’ Health Study II to assess associations between BMI and early-onset colorectal cancer among 85,256 women nurses aged 25 to 42 years.

During 1,196,452 person-years of follow-up, researchers observed 114 cases of early-onset colorectal cancer. Median age at diagnosis was 45 years.

Compared with women who had a BMI of 18.5 kg/m2 to 22.9 kg/m2, the risk for early-onset colorectal cancer was greater among women deemed overweight with a BMI of 25 kg/m2 to 29.9 kg/m2 (RR = 1.37; 95% CI, 0.81-2.3) and women deemed obese with a BMI of 30 kg/m2 or higher (RR = 1.93; 95% CI, 1.15-3.25).

Each 5-unit increment increase in BMI appeared associated with a RR of 1.2 (95% CI, 1.05-1.38; P for trend = .01).

Researchers observed similar associations among women with no family history of colorectal cancer and women who had not had a lower endoscopy within the past 10 years.

When assessing BMI at age 18 years, women with a BMI of 21 kg/m2 to 22.9 kg/m2 had a RR of 1.32 (95% CI, 0.8-2.16) and those with a BMI of 23 kg/m2 or greater had a RR of 1.63 (95% CI, 1.01-2.61) compared with women with a BMI of 18.5 kg/m2 to 20.9 kg/m2.

Compared with women who had gained less than 5 kg or had lost weight since age 18 years, women who gained 20 kg to 39.9 kg had a RR of 1.65 (95% CI, 0.96-2.81) and women who gained 40 kg or more had a RR of 2.15 (95% CI, 1.01-4.55; P for trend = .007).

“The biological mechanisms underlying the association between obesity and colorectal cancer remain unclear,” the researchers wrote. “Metabolic syndrome, insulin resistance, systemic inflammation and immunity are important mediators. Microbial dysbiosis may also contribute.”

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The limitations of the study included lack of data on waist and hip measurements, as well as its inclusion of primarily white women.

“Given that most of these younger cases are diagnosed symptomatically with more advanced tumors and with a significant influence on years of life lost, our findings reinforce the benefits of maintaining a healthy weight throughout life,” the researchers wrote. “Our findings suggest the promise of using body weight to personalize and complement early cancer screening strategies among adults younger than 50 years.” – by Cassie Homer

Disclosures: Liu reports no relevant financial disclosures. One author reports consulting fees from Bayer, Janssen and Pfizer.

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Perspective

The rising incidence of colorectal cancer among younger individuals — those younger than age 50 years — has generated a lot of interest in unraveling the underlying causes. Because there is a relationship between the high-fat Western diet and colorectal cancer, and because there is an “obesity epidemic” in the United States, it makes sense to look into whether there may be a relationship between obesity and risk for early-onset colorectal cancer. It is already known that obesity contributes to colorectal cancer risk among elderly individuals, but older case-control studies and nonprospective studies have not resolved the issue definitively for early-onset colorectal cancer.

Using data from the prospective Nurses’ Health Study II on over 85,000 women nurses aged 25 to 42 years, researchers found that obesity can double the risk for early-onset colorectal cancer. Not only was BMI at age 18 years a factor, but also weight gain after the age of 18 years contributed to the increased risk for colorectal cancer. In the present study, obesity was more strongly associated with early-onset colorectal cancer than for those who developed the cancer later in life, and there was also a stronger association with the onset of rectal vs. colon cancer.

Various underlying mechanisms proposed by the authors that may be involved in the obesity-early-onset colorectal cancer risk — and that remain to be investigated in the future — include metabolic syndrome, insulin resistance, systemic inflammation, immunity, epigenetic mechanisms and microbial dysbiosis. The study would suggest adopting a healthy lifestyle as a measure to limit the potential impact of body weight on colorectal cancer risk, including earlier in life.

Wafik S. El-Deiry, MD, PhD, FACP

HemOnc Today Editorial Board Member
Fox Chase Cancer Center

Disclosure: El-Deiry reports no relevant financial disclosures.