Insulin-like growth factor-1, IGF binding protein-3, and the risk of esophageal cancer in a nested case-control study

doi:10.3748/wjg.v23.i19.3488

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World Journal of Gastroenterology

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Case Control Study

World J Gastroenterol. May 21, 2017; 23(19): 3488-3495
Published online May 21, 2017. doi: 10.3748/wjg.v23.i19.3488

Insulin-like growth factor-1, IGF binding protein-3, and the risk of esophageal cancer in a nested case-control study

Yasushi Adachi, Masanori Nojima, Mitsuru Mori, Kentaro Yamashita, Hiro-o Yamano, Hiroshi Nakase, Takao Endo, Kenji Wakai, Kiyomi Sakata, Akiko Tamakoshi

Yasushi Adachi, Takao Endo, Division of Gastroenterology, Department of Internal Medicine, Sapporo Shirakaba-dai Hospital, Sapporo 062-0052, Japan

Yasushi Adachi, Kentaro Yamashita, Hiro-o Yamano, Hiroshi Nakase, Department of Gastroenterology, Sapporo Medical University, Sapporo 060-8543, Japan

Masanori Nojima, The Institute of Medical Science Hospital, The University of Tokyo, Tokyo 108-8639, Japan

Mitsuru Mori, Department of Public Health, Sapporo Medical University, School of Medicine, Sapporo 060-8556, Japan

Kenji Wakai, Department of Preventive Medicine, Nagoya University, Graduate School of Medicine, Nagoya 466-8550, Japan

Kiyomi Sakata, Department of Hygiene and Preventive Medicine, Iwate Medical University School of Medicine, Yahaba 028-3694, Japan

Akiko Tamakoshi, Department of Public Health, Hokkaido University School of Medicine, Sapporo 060-8638, Japan

Author contributions: Adachi Y analyzed data and wrote the manuscript; Nojima M analyzed data and corrected the manuscript; Yamashita K, Yamano H, and Nakase H advised and checked the manuscript; Endo T helped this study and to write the manuscript; Mori M, Wakai K, Sakata K and Tamakoshi A are the original members of JACC study and advised for this study.

Supported by the Ministry of Education, Culture, Sports, Science, and Technology and from the Ministry of Health, Labour and Welfare, Japan.

Institutional review board statement: The ethical board of the Nagoya University School of Medicine approved this study.

Informed consent statement: Informed consent was obtained from all participants.

Conflict-of-interest statement: The authors have declared no conflicts of interest.

Data sharing statement: No additional data available.

Correspondence to: Yasushi Adachi, MD, PhD, Department of Gastroenterology, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan. yadachi@sapmed.ac.jp

Telephone: +81-11-6112111 Fax: +81-11-6112282

Received: December 29, 2016
Peer-review started: January 3, 2017
First decision: February 10, 2017
Revised: February 25, 2017
Accepted: April 21, 2017
Article in press: April 21, 2017
Published online: May 21, 2017
Processing time: 141 Days and 23.1 Hours

Abstract

AIM

To assess the relationship between serum levels of insulin-like growth factor-1 (IGF1)/IGF-binding protein-3 (IGFBP3) and the risk of esophageal carcinoma.

METHODS

We assessed the relationship between the serum levels of these molecules and the risk of esophageal cancer in a prospective, nested case-control study of participants from the Japan Collaborative Cohort Study. A baseline survey was conducted from 1988 to 1990. Of the 110585 enrolled participants, 35% donated blood samples. Those who had been diagnosed with esophageal cancer were considered cases for nested case-control studies. A conditional logistic model was used to estimate odds ratios for the incidence of esophageal cancer associated with serum IGF1 and IGFBP3 levels.

RESULTS

Thirty-one cases and 86 controls were eligible for the present assessment. The molar ratio of IGF1/IGFBP3, which represents the free and active form of IGF1, was not correlated with the risk of esophageal carcinoma. A higher molar difference between IGFBP3 and IGF1, which estimates the free form of IGFBP3, was associated with a decreased risk of esophageal carcinoma (P = 0.0146), and people in the highest tertile had the lowest risk (OR = 0.107, 95%CI: 0.017-0.669). After adjustment for body mass index, tobacco use, and alcohol intake, the molar difference of IGFBP3-IGF1 was inversely correlated with the risk of esophageal carcinoma (P = 0.0150).

CONCLUSION

The free form of IGFBP3, which is estimated by this molar difference, may be inversely associated with esophageal cancer incidence.

Keywords: Esophageal cancer; Insulin-like growth factor; Insulin-like growth factor binding protein; Nested case-control study; Odds ratio

Core tip: Insulin-like growth factor-1 (IGF1) is a potent mitogen, whereas IGF-binding protein-3 (IGFBP3) binds and inhibits IGF1. High circulating IGF1 and low IGFBP3 are associated with increased risk of several cancers. Here we assessed the relationship between these molecules and the risk of esophageal carcinoma in a prospective, nested case-control study from the Japan Collaborative Cohort Study. Free IGF1, represented by the molar ratio of IGF1/IGFBP3, was not correlated with the risk of esophageal carcinoma. The free form of IGFBP3, which is estimated by the molar difference of IGFBP3-IGF1, may be inversely associated with esophageal cancer incidence.