Soy consumption reduces the risk of non‐small‐cell lung cancers with epidermal growth factor receptor mutations among Japanese

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that activates several signaling pathways resulting in cell proliferation, escape from apoptosis, and increased likelihood of invasion or metastasis, all of which are associated with the cancer phenotype.⁽¹⁾ Elevated levels of EGFR are frequently seen in a variety of epithelial tumors⁽²⁾ including non‐small‐cell lung cancers (NSCLCs)^(3,4) and activating mutations of EGFR such as deletion in Exon 19 or point mutation at codon 858 have been reported in a subset of NSCLCs which are usually highly sensitive to kinase inhibitors such as gefitinib and erlotinib.^(5–7) Moreover, striking correlations between the EGFR mutation status and characteristics like a non‐smoking background, adenocarcinoma‐type, female sex, and East Asian ethnicity have been repeatedly demonstrated^(5–9) albeit without clarification of the reasons as yet. Previously, we demonstrated a significance of female sex and reproductive factors for risk of EGFR mutated (EGFR^mut) NSCLCs and suggested possible involvement of estrogenic factors in their genesis.⁽¹⁰⁾ Considering several pathological studies also demonstrated expression of hormonal receptors in NSCLCs, our former results motivated us to examine the impact of soy consumption, a primary source of the isoflavone phytestrogens well known to be associated with the hormone‐related breast cancer.^(11–14)

Here, to assess the significance of dietary soy consumption with reference to the EGFR status of NSCLCs, in parallel with other food items, we conducted a case‐control study in 353 patients with NSCLCs and 1765 matched controls in a Japanese population.

Materials and Methods

Study subjects.  Subjects for this study were part of those in the previous report.⁽¹⁰⁾ A total of 353 patients diagnosed as having primary NSCLCs at the Department of Thoracic Surgery, Aichi Cancer Center Hospital (ACCH) and treated between January 2001 and February 2005 and 1765 age‐ and sex‐matched (1:5 case‐control ratio) non‐cancer patients who visited ACCH during the same period were examined. The reason for exclusion of the other 82 cases was lack of diet information by semiquantitative food‐frequency‐questionnaire (SQFFQ). Correspondingly, 410 matched‐controls were excluded. All the cases underwent potentially curative pulmonary resection at the Department of Thoracic Surgery, ACCH. The distribution of histological subtypes for...