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Gastroenterology. 2018 Nov;155(5):1474-1482.e1. doi: 10.1053/j.gastro.2018.07.033. Epub 2018 Aug 1.

Increased Levels of Branched-Chain Amino Acid Associated With Increased Risk of Pancreatic Cancer in a Prospective Case-Control Study of a Large Cohort.

Author information

1
Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
2
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.
3
Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan. Electronic address: moiwasak@ncc.go.jp.
4
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan; Metabolomics Research, Department of Internal Related, Kobe University Graduate School of Medicine, Hyogo, Japan; AMED-CREST, AMED, Hyogo, Japan.

Abstract

BACKGROUND & AIMS:

A marker is needed to identify individuals at risk for pancreatic cancer. Increases in branched-chain amino acids (BCAAs) have been associated with pancreatic cancer. We performed a prospective case-control study to study the association between plasma BCAA levels and risk of pancreatic cancer in a large cohort.

METHODS:

We conducted a nested case-control study selected from 30,239 eligible participants 40-69 years old within the Japan Public Health Center-based prospective study. Over 16.4 years, 170 newly diagnosed pancreatic cancer cases were identified. Each case was matched to 2 controls by age, gender, geographic area, and fasting time at blood collection. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer were calculated using conditional logistic regression models with adjustment for potential confounding factors.

RESULTS:

Increased plasma BCAA levels at baseline were associated with an increased risk of pancreatic cancer. Compared with the lowest quartile of BCAA levels, the OR in the highest quartile was 2.43 (95% CI 1.21-4.90), and the OR per 1 SD increase in BCAA levels was 1.32 (95% CI 1.05-1.67). The association was especially strong for cases with blood samples collected at least 10 years before cancer diagnosis (OR per SD 1.60, 95% CI 1.10-2.32) compared with those detected less than 10 years before diagnosis (OR per SD 1.16, 95% CI 0.86-1.57).

CONCLUSIONS:

In an analysis of data from the Japan Public Health Center-based prospective study, we found an association between increased plasma BCAA level and increased risk of pancreatic cancer-particularly when the increase in BCAAs was observed at least 10 years before diagnosis. These findings add to the growing body of evidence for the association between BCAA levels and pancreatic cancer risk.

KEYWORDS:

Metabolites; Metabolome; Pancreas; Tumorigenesis

PMID:
30076838
DOI:
10.1053/j.gastro.2018.07.033
[Indexed for MEDLINE]

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