Pancreatic Cancer Risk in Adulthood Affected by Weight During Adolescence

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Adolescent obesity may increase the risk of pancreatic cancer later in life with up to a four-fold increased risk.

This is the conclusion of a study published early online in CANCER, a peer-reviewed journal of the American Cancer Society. The study’s results also suggest that overweight and even higher weight within the normal weight range in men may increase pancreatic cancer risk in a graded manner.[1]

Risk and Incidence
Pancreatic cancer, the sixth most common cause of cancer-related deaths in the world, is one of the most fatal cancers in adult men and women. Unfortunately, most patients are diagnosed with advanced disease.


The overall population attributable fraction of pancreatic cancer due to adolescent overweight and obesity was 11% among this Israeli Jewish population…


In the United States, the disease accounts for about 3% of all cancers in the US and about 7% of all cancer deaths. According to estimates from the American cancer Society, about 55,440 people (29,200 men and 26,240 women) will be diagnosed with pancreatic cancer in 2018 and about 44,330 people (23,020 men and 21,310 women) will die of the disease. On average, 75% of all patients die within one year of diagnosis. The current 5-year survival is estimated to be 6%.[2][3]

Studies have linked adult obesity, one of the few modifiable risk factors of pancreatic cancer, with an increased risk for its occurrence. In addition, obesity is also linked to an increased risk of diabetes, a condition that in turn has been associated as a separate risk factor for pancreatic cancer.[3]

In addition to obesity and diabetes, other known factors associated with increased pancreatic cancer risk include smoking, excessive alcohol consumption, increasing age, family history and several rare genetic syndromes.[3][4]

A pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium linked pancreatic cancer mortality with measures of central adiposity. [5]

The analysis confirmed that higher waist-to-hip ratio (HR = 1.09, 95% CI 1.02–1.17 per 0.1 increment) and waist circumference (HR = 1.07, 95% CI 1.00–1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. The researchers found that Body Mass Index (BMI) during early adulthood was associated with increased pancreatic cancer mortality (HR = 1.18, 95% CI 1.11–1.25 per 5 kg/m2), with increased risk observed in both overweight and obese individuals (compared with BMI of 21.0 to <23 kg/m2, HR = 1.36, 95% CI 1.20–1.55 for BMI 25.0 < 27.5 kg/m2, HR = 1.48, 95% CI 1.20–1.84 for BMI 27.5 to <30 kg/m2, HR = 1.43, 95% CI 1.11–1.85 for BMI ≥30 kg/m2). However, they also observed that BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR = 1.05, 95% CI 1.01–1.10 per 5 kg/m2). [5]

Adolescent weight
To further uncover any potential associations with adolescent weight, Zohar Levi, MD, of Rabin Medical Center and Tel Aviv University, and his colleagues analyzed 1,087,358 Israeli Jewish men and 707,212 Jewish women who underwent a compulsory physical examination between the ages of 16 and 19 years from 1967 to 2002. Pancreatic cancer incidence through 2012 was identified by linkage to the Israeli National Cancer Registry.

Over a median of 23.3 years of follow up, 551 new cases of pancreatic cancer cases were identified, including 423 cancers among men and 128 cancers among women. Compared with normal weight (5th to <85th percentile), obesity (≥95th percentile) was associated with a 3.67-times higher cancer risk among men and a 4.07-times higher risk among women.

Among men, high-normal BMI (≥75th to <85th percentile) and overweight (85th to <95th percentile) were associated with 49% and 97% higher risks for cancer, respectively, compared with low-normal BMI (≥5th to <25th percentile).

“The overall population attributable fraction of pancreatic cancer due to adolescent overweight and obesity was 11% among this Israeli Jewish population,” Levi said.

An accompanying editorial by Chanan Meydan, MD, of the Mayanei Hayeshua Medical Center in Israel, highlights systemic inflammation caused by obesity as a potential driver behind the development of pancreatic cancer.

Reference
[1] Levi Z, Rottenberg Y, Twig G, Katz L, Leiba A, Derazne E, Tzur D, Eizenstein S, Keinan-Boker L, Afek A, Kark JD. Adolescent overweight and obesity and the risk for pancreatic cancer among men and women. A nationwide study of 1.79 Million Israeli adolescents. . CANCER; Published Online: November 12, 2018 (DOI: 10.1002/cncr.31764).
[2] Key Statistics for Pancreatic Cancer. How common is pancreatic cancer? American Cancer Society. Online. Last accessed November 7, 2018
[3] Bracci PM. Obesity and pancreatic cancer: overview of epidemiologic evidence and biologic mechanisms.Mol Carcinog. 2012 Jan;51(1):53-63. doi: 10.1002/mc.20778. [Article]
[4] Genkinger JM, Kitahara CM, Bernstein L, Berrington de Gonzalez A, Brotzman M, Elena JW, Giles GG, Hartge P, et al. Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies. 2015 Nov;26(11):2257-66. doi: 10.1093/annonc/mdv355. Epub 2015 Sep 7.
[5] Michaud DS.Obesity and Pancreatic Cancer Recent Results Cancer Res. 2016;208:95-105.


Last Editorial Review: November 12, 2018

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