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Excess body weight earlier in life may have greater influence on pancreatic cancer mortality risk
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ATLANTA — Excess body weight before age 50 years may increase pancreatic cancer mortality risk to a greater degree than excess weight at older ages, according to results from the Cancer Prevention Study II presented at American Association for Cancer Research Annual Meeting.
“Pancreatic cancer rates have been steadily increasing since the early 2000s,” Eric J. Jacobs, PhD, senior scientific director of epidemiology research at American Cancer Society, said in a press release. “We’ve been puzzled by that finding because smoking — a major risk factor for pancreatic cancer — is declining.”
Although pancreatic cancer is relatively rare, representing a little more than 3% of all new cancer cases, it is a particularly fatal, with only 8.5% of patients achieving 5-year survival. It is the third leading cause of cancer death in the United States, after lung and colon cancer.
Previous studies have found weak associations between BMI and risk for pancreatic cancer; however, most of these studies measured BMI in older adulthood, which may reflect body fat gained too late to affect risk over an average lifetime.
In the nationwide, prospective cohort study, Jacobs and colleagues evaluated data on 963,317 adults aged 30 to 89 years at the time of enrollment in American Cancer Society’s Cancer Prevention Study II, which followed participants from 1982 through 2014. Researchers calculated BMI from height and weight at time of enrollment.
During follow-up, 8,354 participants died of pancreatic cancer.
The researchers used multivariable proportional hazards regression models to determine HRs for BMI. Additionally, they used HRs from Cancer Prevention Study II and BMI data from National Health and Nutrition Examination Surveys to determine population-attributable fractions by birth cohort.
Results showed declines in HRs with increasing age at BMI assessment. An increase of five BMI units appeared associated with the following HRs at age of assessment: aged 30 to 49 years, 1.25 (95% CI, 1.18-1.33); aged 50 to 59 years, 1.19 (95% CI, 1.14-1.23); aged 60 to 69 years, 1.14 (95% CI, 1.08-1.21), and aged 70 to 89 years, 1.13 (95% CI, 1.02-1.26; P for trend = .005).
More recent U.S. birth cohorts showed a substantially higher prevalence of obesity in early middle age than earlier cohorts. The researchers then estimated that, based on a HR of 1.25 per five BMI units at age 45 years, 28% of pancreatic cancer deaths among Americans born between 1970 and 1974 will be attributable to BMI levels of 25 kg/m2 or greater. This is nearly double the corresponding percentage among those born in the 1930s, who were less inclined to be obese in early middle age.
“Our results strongly suggest that to stop and eventually reverse recent increases in pancreatic cancer rates, we will need to do better in preventing excess weight gain in children and younger adults, an achievement which would help prevent many other diseases as well,” Jacobs said in the press release. – by Jennifer Byrne
Reference:
Jacobs EJ, et al. Abstract 3281/28. Presented at: AACR Annual Meeting; March 29-April 3, 2019; Atlanta.
Disclosures: Jacobs and the other study authors report no relevant financial disclosures.
Perspective
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Laleh Melstrom, MD, MS
Aside from genetic mutations and risk factors — such as smoking, diabetes and lack of vitamin D — causative factors for pancreatic cancer have not been defined. This study is valuable and unique in that it followed people longitudinally for over 4 decades, and it revealed not only the association of obesity with the risk for pancreatic cancer but, more importantly, the timing of obesity in relation to this risk.
The risk seems to be much higher if an individual is obese or heavier when they are younger, and the risk appears to be compounded with age. People in their 40s who are obese have an increased risk compared with people in their 50s or 60s. This is an important finding, and emphasizes the need to intervene now in children and young adults to promote healthy body weight. Obesity doesn’t only have implications for pancreatic cancer; it also has implications for breast cancer, endometrial cancer and colon cancer — all of which have a well-established association with BMI.
The reason for the association between BMI and pancreatic cancer in younger individuals is not entirely understood. It can be surmised that because the job of the pancreas is to help us digest food with enzymatic secretions and release insulin, obesity by default causes the pancreas to work harder. If your pancreas is working harder in your 20s, 30s, 40s and 50s, that’s a lifetime of excess strain on the gland. It’s also been suggested that obesity leads to more circulating cancer-causing metabolites that put the body at risk for developing pancreatic cancer. Causation has only been described in the context of additive mutations over time and clearly this study demonstrates that there is a longitudinal risk over time.
Pancreatic cancer is currently the third-leading cause of cancer death, and this study highlights from a public policy perspective that more effort needs to be placed on promoting activity among children, healthy body weight among young adults, and more attention to healthy lifestyles and preventive measures. We are not necessarily going to feel those effects immediately, but 20, 30, 40 years down the road, our entire society is going to shoulder the burden of care for these future patients with cancer who did not appropriately engage in or receive preventive care in their youth. This is one of many studies to show that our health in early adulthood and middle age really has long-lasting implications for our later years and the health of our society as a whole.
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