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Alexander M. Castellino, PhD
A national Israeli study found that obese people in adolescence had about four times higher risk of developing pancreatic cancer later in life; those who were overweight had a two-fold risk.
The study analyzed data relating to nearly 1.8 million adolescents followed for 23 years.
"This is the largest analysis to date of measures of adolescent obesity in association with the risk of pancreatic cancer," say the authors, led by Zohar Levi, MD, MHA, Rabin Medical Center, Tikva, Israel.
"We observed that BMI [body mass index] at age 17 was significantly and positively associated with pancreatic cancer in early adulthood in men and women, "they note.
The study also indicates that the association with pancreatic cancer is dose-related and that the highest percentiles in the high body mass index group are associated with higher risk probabilities. Minimal risk has been observed in individuals with a BMI of 19.8 kg / m2; significantly elevated risks were observed at values above 23.0 mg / m2.
The study was published online on November 12 in Cancer.
An accompanying editorial suggests that study is important for two reasons. Since the study used two large, relatively complete Israeli databases, the results could be extrapolated to the Israeli population in general. In addition, the study confirms the findings of other studies establishing that obesity is a risk factor for pancreatic cancer.
"The identification of risk factors for this disease entity is essential because, to date, these factors have been attributed to only a small portion of the patient population and include a variety of biological, social and hereditary risk factors, although they represent only modest increases in risk, "writes columnist Chanan Meydan, MD, of the Department of Internal Medicine, Mayanei HaYeshua Medical Center, in Bnei Brak, Israel.
Details of the study
The researchers linked two large Israeli databases. One of them was the database of Israeli Jewish teens aged 16 to 19 who underwent a mandatory exam in the late teens to determine their fitness for service military. The other was the database of the Israeli National Cancer Registry, from which only verified reports of pancreatic adenocarcinoma were included.
For analysis, the researchers grouped the BMI values into percentiles established by the Center for Disease Control and Prevention (CDC) classification: <5th percentile was considered insufficient; The reference group consisted of the 5th to the <85th percentile ("normal" weight); From the 85th to the 95th percentile was considered overweight; and 95th percentile or higher was considered obese.
The study included an analysis of 1,794,570 individuals (1,087,358 men, 707,212 women). The average age of the participants at the time of the initial examination was 17 years old.
According to the CDC-BMI classification, 54,224 people (3%) were obese and 140,467 people (7.8%) were overweight.
After a median follow-up of 23.3 years (44,563,618 person-years), 551 cases of pancreatic cancer were identified (423 in men, 128 in women). The median age at diagnosis was 51 years old.
The cumulative Kaplan-Meier incidence of pancreatic cancer curves showed a divergence at about 25 years' follow-up.
The risk ratios for pancreatic cancer were as follows (95% confidence intervals are shown in parentheses):
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For obese people in the total population: 3.89 (2.76 – 5.50)
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For overweight people in the total population: 1.68 (1.27 – 2.21)
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For obese men: 3.67 (2.52 – 5.34)
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For overweight men: 1.86 (1.36 – 2.45)
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For obese women: 4.07 (1.78 – 9.29)
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For overweight women: 1.21 (0.66 to 2.26)
Based on an analysis of BMI percentiles, people with a high normal BMI also have an increased risk of pancreatic cancer compared to people with a low normal BMI.
Similar results emerged when researchers used the BMI classification in four groups of the World Health Organization instead of the CDC-BMI classification.
Country of birth, country of origin and socio-economic status were not associated with increased risk.
Limits of study
Researchers recognize several limitations of their study. As weight change over time was not available, it was not possible to determine the relationship between pancreatic cancer risk and weight change over time. An analysis of the risk of pancreatic cancer with hip-size ratio or waist circumference, which is an independent correlate of pancreatic cancer, was also not possible due to lack of information.
Information on other confounding factors (smoking, alcohol consumption, diabetes, physical activity, dietary composition, BRCA mutation status) was not available and therefore their contribution to the risk of pancreatic cancer could not be assessed. However, researchers note that BRCA mutations, associated with an increased risk of pancreatic cancer, are present in approximately 2% of Ashkenazi Jews.
Meydan also notes in his editorial the limitations inherent in large data analysis. "The fundamental questions asked by researchers are sometimes established long after the data has been collected, formulated and is waiting to be unveiled," Meydan writes. "In this way, the initial tenants of the database may not meet the future needs of researchers, which limits the relevance," he adds.
Comments of the editorialist
Meydan notes that Israel's vast population-based databases reflect a developing society from rural to urban areas, from austerity to economic boom, from physical labor to sedentary occupations, all linked to a gradual increase in prevalence of obesity.
Meydan assumes that obesity is a component of the metabolic syndrome, which is emerging as a modifying factor for the pathogenesis of pancreatic cancer and "should be considered as part of the spectrum of inflammation".
The object of obesity is going from a vasculopathy to a dysmetabolism, suggests Meydan. He notes that an increasing body of evidence suggests that adipose tissue is an organ of the endocrine system, with adiponectin and leptin mediators of adipocyte regulation; Adiponectin influences insulin resistance and leptin on hunger. He points out that the signaling pathways associated with non-coding RNA are associated with the pathogenesis of pancreatic cancer.
"In the context of pancreatic cancer, these molecular elements [metabolic syndrome, inflammation, noncoding RNA] emerging as diagnostic, prognostic and therapeutic roles, "notes Meydan.
The study was funded by research grants from the Cancer Research Fund in Israel (New York) and the Environment and Health Fund (Jerusalem, Israel). The authors of the study did not reveal any relevant financial relationship. Dr. Meydan received a personal fee from Raziel Therapeutics Ltd.
Cancer. Posted online November 12, 2018. Abstract, Editorial
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