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Albanes, Demetrius; Alcala, Karine; Alcala, Nicolas; Amos, Christopher I.; Arslan, Alan A.; Bassett, Julie K.; Brennan, Paul; Cai, Qiuyin; Chen, Chu; Feng, Xiaoshuang; Freedman, Neal D.; Guida, Florence; Hung, Rayjean J.; Hveem, Kristian; Johansson, Mikael; Johansson, Mattias; Koh, Woon-Puay; Langhammer, Arnulf; Milne, Roger L.; Muller, David; Onwuka, Justina; Sørgjerd, Elin Pettersen; Robbins, Hilary A.; Sesso, Howard D.; Severi, Gianluca; Shu, Xiao-Ou; Sieri, Sabina; Smith-Byrne, Karl; Stevens, Victoria; Tinker, Lesley; Tjønneland, Anne; Visvanathan, Kala; Wang, Ying; Wang, Renwei; Weinstein, Stephanie; Yuan, Jian-Min; Zahed, Hana; Zhang, Xuehong; Zheng, Wei
Nature communications, 06/2023, Volume: 14, Issue: 1Journal Article
Identification of risk biomarkers may enhance early detection of smoking-related lung cancer. We measured between 392 and 1,162 proteins in blood samples drawn at most three years before diagnosis in 731 smoking-matched case-control sets nested within six prospective cohorts from the US, Europe, Singapore, and Australia. We identify 36 proteins with independently reproducible associations with risk of imminent lung cancer diagnosis (all p < 4 × 10 ). These include a few markers (e.g. CA-125/MUC-16 and CEACAM5/CEA) that have previously been reported in studies using pre-diagnostic blood samples for lung cancer. The 36 proteins include several growth factors (e.g. HGF, IGFBP-1, IGFP-2), tumor necrosis factor-receptors (e.g. TNFRSF6B, TNFRSF13B), and chemokines and cytokines (e.g. CXL17, GDF-15, SCF). The odds ratio per standard deviation range from 1.31 for IGFBP-1 (95% CI: 1.17-1.47) to 2.43 for CEACAM5 (95% CI: 2.04-2.89). We map the 36 proteins to the hallmarks of cancer and find that activation of invasion and metastasis, proliferative signaling, tumor-promoting inflammation, and angiogenesis are most frequently implicated.
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