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

Katagiri, Ryoko; Goto, Atsushi; Nakagawa, Takashi; Nishiumi, Shin; Kobayashi, Takashi; Hidaka, Akihisa; Budhathoki, Sanjeev; Yamaji, Taiki; Sawada, Norie; Shimazu, Taichi; Inoue, Manami; Yoshida, Masaru; Tsugane, Shoichiro

doi:10.1053/j.gastro.2018.07.033

Cited by 61 publications

(43 citation statements)

References 26 publications

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“…In the same line, although not validated, we found that the levels of glycerol-3-phosphate were significantly lower in cases than in controls (FDR q < 0.25). The other two studies, one in Japanese (43) and one in European descendants (44), showed that the levels of branched-chain amino acid including isoleucine, leucine, and valine were significantly higher in cases than in controls. However, we did not observe this association.…”

Section: Discussionmentioning

confidence: 94%

A Prospective Targeted Serum Metabolomics Study of Pancreatic Cancer in Postmenopausal Women

Jiao

Maity

Coarfa

et al. 2019

Cancer Prevention Research

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To examine the association between metabolic deregulation and pancreatic cancer, we conducted a two-stage case-control targeted metabolomics study using prediagnostic sera collected one year before diagnosis in the Women's Health Initiative study. We used the LC/MS to quantitate 470 metabolites in 30 matched case/control pairs. From 180 detectable metabolites, we selected 14 metabolites to be validated in additional 18 matched case/control pairs. We used the paired t test to compare the concentrations of each metabolite between cases and controls and used the log fold change (FC) to indicate the magnitude of difference. FDR adjusted q-value < 0.25 was indicated statistically significant. Logistic regression model and ROC curve analysis were used to evaluate the clinical utility of the metabolites. Among 30 case/control pairs, 1-methyl-L-tryptophan (L-1MT) was significantly lower in the cases than in the controls (log 2 FC ¼ À0.35; q-value ¼ 0.03). The area under the ROC curve was 0.83 in the discrimination analysis based on the levels of L-1MT, acadesine, and aspartic acid. None of the metabolites was validated in additional independent 18 case/control pairs. No significant association was found between the examined metabolites and undiagnosed pancreatic cancer.

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Section: Discussionmentioning

confidence: 94%

A Prospective Targeted Serum Metabolomics Study of Pancreatic Cancer in Postmenopausal Women

Jiao

Maity

Coarfa

et al. 2019

Cancer Prevention Research

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“…The BCAA metabolism and BCAT1 activity (enzyme involved in the first step of BCAA catabolism) could play functional roles in the progression of tumors (4) . Increased levels of plasma BCAAs were associated with an increased risk of pancreatic cancer in a nested case-control study of a Japan cohort (3) . They were also positively related to obesity, diabetes and insulin resistance (13; 14; 15) , which are known risk factor for CRC (16; 17) .…”

Section: Discussionmentioning

confidence: 97%

Dietary intake of branched-chain amino acids and colorectal cancer risk

et al. 2020

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ABSTACT An adequate intake of branched-chain amino acids (BCAAs) is required for protein synthesis and metabolic functions, including insulin metabolism. Emerging studies found positive associations between BCAAs and the risk of various diseases sharing etiological aspects with colorectal cancer (CRC), including type 2 diabetes, obesity, and pancreatic cancer. We investigated the relation between dietary BCAAs and CRC using data from a multicentric Italian case-control study, including 1953 cases of CRC (of these, 442 of sigmoid colon) and 4154 hospital controls with acute, non-neoplastic diseases. A validated food-frequency questionnaire was used to estimate the participants’ usual diet and to assess dietary intakes of various nutrients, including energy, BCAAs and calcium. Odds ratio (ORs) and corresponding confidence intervals (CI) were computed by multiple logistic regression models adjusted for age, sex and other confounding factors, including total energy intake. BCAA intake was inversely related to CRC risk (OR for the highest versus the lowest quintile, 0.73; 95% CI, 0.55-0.97), but the association was attenuated after adjustment for calcium intake (OR, 0.90; 95% CI, 0.65-1.25). A linear inverse association with sigmoid colon cancer risk remained also after adjustment for other dietary factors, including calcium intake (OR, 0.49; 95% CI, 0.27-0.87). This study provides supporting evidence that higher levels of dietary BCAA intake are not associated with an increase of CRC risk, but confirms that they may be related to a reduced risk of sigmoid colon cancer.

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“…Although most studies have shown that BCAT1 is primarily expressed in brain, our data demonstrates that the BCAT1 protein is most abundant in pancreas, in addition to its presence in the brain. Recent studies showed that BCAA level spikes years before pancreas cancer, possibly suggesting that BCAA metabolism disorder might contribute to cancer development (35,36).…”

Section: Branched Chain Amino Acid Metabolismmentioning

confidence: 99%

A Quantitative Proteome Map of the Human Body

Jiang

Wang

Lin

et al. 2019

Preprint

109

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Quantitative proteome study of 32 human tissues and integrated analysis with transcriptome data revealed that understanding protein levels could provide in-depth knowledge to post transcriptional or translational regulations, human metabolism, secretome, and diseases. AbstractDetermining protein levels in each tissue and how they compare with RNA levels is important for understanding human biology and disease as well as regulatory processes that control protein levels. We quantified the relative protein levels from 12,627 genes across 32 normal human tissue types prepared by the GTEx project. Known and new tissue specific or enriched proteins (5,499) were identified and compared to transcriptome data. Many ubiquitous transcripts are found to encode highly tissue specific proteins. Discordance in the sites of RNA expression and protein detection also revealed potential sites of synthesis and action of protein signaling molecules. Overall, these results provide an extraordinary resource, and demonstrate that understanding protein levels can provide insights into metabolism, regulation, secretome, and human diseases.

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

Cited by 61 publications

References 26 publications

A Prospective Targeted Serum Metabolomics Study of Pancreatic Cancer in Postmenopausal Women

A Prospective Targeted Serum Metabolomics Study of Pancreatic Cancer in Postmenopausal Women

Dietary intake of branched-chain amino acids and colorectal cancer risk

A Quantitative Proteome Map of the Human Body

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