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

Abstract

Epidermal growth factor receptor (EGFR) mutations play substantial roles in genesis and proliferation of non-small-cell lung cancers (NSCLCs).We recently found that reproductive factors have a substantial impact on risk of development of NSCLCs featuring such EGFR mutations. Therefore, we explored the influence of dietary habits on NSCLC risk with reference to the EGFR mutational status. We conducted a case-control study using 353 patients with NSCLCs (122 EGFR mutated and 231 EGFR wild-type) and 1765 age-sex matched non-cancer control subjects. Dietary exposure was based on a semiquantitative food frequency questionnaire and impact of major food items, like meats, seafoods, vegetables and soybean products was assessed by multivariate logistic regression. Soybean products demonstrated a protective association with EGFR mutated, but not EGFR wild-type NSCLCs, with multivariate-adjusted odds ratios and 95% confidence intervals for the 2nd and 3rd tertile of soybean product consumption of 0.79 (0.50-1.27) and 0.56 (0.34-0.93) relative to those in the lowest tertile (trend P = 0.023). In conclusion, soy consumption may exert a protective association against the development of NSCLCs with EGFR mutations, providing possible insights into mechanisms of their genesis. (Cancer Sci 2008; 99: 1202-1208) T he 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)(6)(7)(8)(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)(12)(13)(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 MethodsStudy subjects. Subjects for this study...

Age at diagnosis predicts outcomes in gefitinib-treated female patients with non-small-cell lung cancer

“…A report from Japanese researchers might partly explain the results of the current study [28]. Matsuo et al reported the incidence of EGFR mutations for each sex, together with mean age [28].…”

Plasma Isoflavones and the Risk of Lung Cancer in Women: A Nested Case–Control Study in Japan

“…Genistein inhibited growth of NSCLC cell lines, particularly one with mutated EGFR (16). Furthermore, a case-control study in Japan found that soy food intake was inversely associated with EGFRmutated NSCLC only (41). Although information was not available on the EGFR status of lung cancer in our study, the present participants had characteristics similar to those associated with the EGFR mutation, that is, never-smoking status, East Asian ethnicity, and female sex (42).…”

EGFR exon 19 in‐frame deletion and polymorphisms of DNA repair genes in never‐smoking female lung adenocarcinoma patients

“…Furthermore, considering the possible multifactorial nature of the etiology of EGFR mutations, future investigations should consider effects of both host genetic susceptibilities and environmental exposures on the occurrence of EGFR mutations because endogenous and exogenous environmental factors such as soybean product consumption, 49 hormones and metabolites, exposure to oil fumes and environmental tobacco smoke 50 may also influence the development of EGFR mutations. Because information on these environmental exposures was not available in this study, gene-environment interactions could not be assessed.…”