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

Abstract

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.

Role of Branched-chain Amino Acid Metabolism in Tumor Development and Progression

“…Third, an ex vivo/in vitro report [69] demonstrated that isoleucine, in a mouse liver metastatic colon cancer model, partly exerted antiangiogenic effects via the mTOR pathway by inhibiting (VEGF) synthesis. In line with these observations, two recent epidemiological reports from Italy [70] and the United States [71] found a modest inverse relationship between dietary BCAA intake and CRC. In another study, branched-chain α-keto acid dehydrogenase (BCKDH) expression has been linked to CRC tumorigenesis via the mitogen-activated protein kinase (MAPK) pathway ex vivo [72].…”

Blood Bacterial DNA Load and Profiling Differ in Colorectal Cancer Patients Compared to Tumor-Free Controls

“…Although this result should be interpreted with caution given the reduced number of cases, various etiological factors and biological aspects are different according to CRC sites. Physical activity, antibiotic use and family history of CRC are relevant in colon but not in rectal cancer [ 37 , 38 , 39 , 40 ], and associations of some dietary components are stronger for some colon subsites cancers [ 41 , 42 ]. Moreover, the proximal and distal colon have a different embryological origin, also resulting in a distinct vascular supply [ 43 ].…”

Blood bacterial DNA, intestinal adenoma and colorectal cancer

“…Along this line, various factors and biological aspects were different according to CRC sites. Physical activity, antibiotic use and family history of CRC were relevant in colon but not in rectal cancer [52,53,54,55], and associations of some dietary components were found to be stronger for the cancer of some colon subsites [56,57]. Moreover, the proximal and distal colon have a different embryological origin, also resulting in a distinct vascular supply [58].…”