Journal
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Volume 23, Issue 3, Pages 461-468Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-13-0770
Keywords
-
Funding
- ISCIII RCESP [C03/09]
- ISCIII of the Spanish Ministry of Health [RETICC DR06/0020]
- ISCIII RCESP [C03/09]
- ISCIII of the Spanish Ministry of Health [RETICC DR06/0020]
- Cancer Research UK [16491] Funding Source: researchfish
- Medical Research Council [MC_U106179471, MC_UU_12015/1, MC_UU_12013/2] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10135] Funding Source: researchfish
- MRC [MC_UU_12015/1, MC_UU_12013/2] Funding Source: UKRI
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
Ask authors/readers for more resources
Background: Imbalances in tryptophan metabolism have been linked to cancer-related immune escape and implicated in several cancers, including lung cancer. Methods: We conducted a nested case-control study within the European Prospective Investigation into Cancer andNutrition (EPIC) that included 893 incident lung cancer cases and 1,748matched controls. Circulating levels of tryptophan and six of its metabolites were measured and evaluated in relation to lung cancer risk. Results: Tryptophan (P-trend = 2 Chi 10(-5)) and the kynurenine/ tryptophan ratio (KTR; P-trend 4 Chi 10(-5)) were associated with lung cancer risk overall after adjusting for established risk factors. The ORs comparing the fifth and first quintiles (OR5th (vs. 1st)) were 0.52 [ 95% confidence interval (CI), 0.37-0.74] for tryptophan and 1.74 (95% CI, 1.24-2.45) for KTR. After adjusting for plasma methionine (available fromprevious work, which was strongly correlated with tryptophan), the associations of tryptophan (adjusted P-trend 0.13) and KTR (P-trend = 0.009) were substantially attenuated. KTR was positively associated with squamous cell carcinoma, the OR5th vs. 1st being 2.83 (95% CI, 1.62-4.94, P-trend -3 Chi 10(-5)) that was only marginally affected by adjusting for methionine. Conclusions: This study indicates that biomarkers of tryptophan metabolism are associated with subsequent lung cancer risk. Although this result would seem consistent with the immune system having a role in lung cancer development, the overall associations were dependent on methionine, and further studies are warranted to further elucidate the importance of these metabolites in lung cancer etiology. Impact: This is the first prospective study investigating the tryptophan pathway in relation to lung cancer risk.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available