Abstract 2585: Dietary isoflavone intake and lung cancer risk: an analysis using data from the prostate, lung, colorectal, and ovary (PLCO) trial
Authors: Wang Qian , Ru Meng , Boffetta Paolo 
Published: July 2021

Abstract
Introduction: Dietary isoflavones are mainly from soy-based foods and are widely consumed in Asian countries. Isoflavone has a similar chemical structure to estrogen and has been suggested to decrease the risk of breast cancer by acting as an estrogen antagonist. Lung cancer development was also suggested to be affected by estrogen signaling. We aim to explore isoflavone intake and lung cancer risk using the prospective PLCO trial.
Methods: Data regarding dietary intake using the food frequency questionnaire, demographic and reproductive information and lung cancer diagnosis were extracted. The associations between lung cancer risk and isoflavone intake (in quartiles) overall and stratified by gender and smoking status were calculated using the Cox proportional hazard models adjusting for potential confounders. SAS 9.4 were used to perform all statistical analyses.
Results: During the 1,215,948 person-year follow-up, a total of 1,706 lung cancer cases were diagnosed. Overall (Table), the highest quartile of isoflavone intake was associated with 26% reduced risk of lung cancer compared to the lowest quartile. When the analysis was stratified by gender and further by smoking status (never vs ever), the decreased risk was only observed among male ever smokers (Q4 vs Q1: HR=0.78, 95%CI: 0.64-0.96) but not their female counterparts (Q4 vs Q1: HR=0.85, 95%CI: 0.68-1.08).
Discussion: This is the first prospective cohort study investigating isoflavone intake and lung cancer risk and we found a protective effect of isoflavone intake against lung cancer risk particularly among male ever smokers, despite an overall lower isoflavone intake among the US populations compared to the Asian populations. Future studies are needed to replicate these results in independent cohorts and shed a light on the potential mechanism of the protective effect of isoflavones on lung carcinogenesis and the interactions between isoflavones, smoking and endogenous estrogens.
Table. Multivariate-adjusted hazard ratios (HRs) for lung cancer risk according to intake of isoflavones stratified by gender and smoking statusQuartiles of isoflavone intakeP for trendQ1Q2Q3Q4Overall No. of cases574413382337 Person-years322,453290,995302,050300,449 HR 95%CIaReference0.91 (0.80-1.03)0.88 (0.77-1.01)0.84 (0.73-0.98)0.56Men Overall No. of cases344251223194 Person-years168,817142,536138,872145,416 HR 95%CIbReference0.95 (0.81-1.13)0.94 (0.78-1.12)0.83 (0.68-1.02)0.36Never smokers No. of cases10161413 Person-years58,70954,63355,67259,906 HR 95%CIcReference1.92 (0.86-4.27)1.77 (0.76-4.09)1.69 (0.68-4.21)0.86Ever smokers No. of cases334235209181 Person-years110,10887,90383,20085,510 HR 95%CIdReference0.96 (0.81-1.14)0.96 (0.80-1.15)0.78 (0.64-0.96)0.08Womene Overall No. of cases230162159143 Person-years153,637148,459163,178155,033 HR 95%CIReference0.85 (0.69-1.04)0.82 (0.66-1.01)0.85 (0.68-1.08)0.92 Never smokers No. of cases23201728 Person-years84,77085,85896,08491,777 HR 95%CIReference0.89 (0.48-1.66)0.74 (0.38-1.42)1.37 (0.73-2.56)0.65 Ever smokers No. of cases207142142115 Person-years68,86662,60167,09563,257 HR 95%CIReference0.88 (0.71-1.10)0.83 (0.66-1.05)0.80 (0.66-1.03)0.87Abbreviations: Q1: (first) lowest quartile; Q2: second quartile; Q3: third quartile Q4: (fourth) highest quartile; HR: hazard ratioaModel = Model c + smoking status + genderbModel = Model c +smoking statuscModel adjusted for age, race, BMI, marital status, education level, alcohol use, family history of any cancer, daily energy intake, vitamin C intake, vitamin E intake and beta-carotene intake.dModel = Model c +pack-year of smokingeAll models among women additionally adjusted for age at menarche, age at menopause and use of hormonal replacement therapy (yes/no).
Citation Format: Qian Wang, Meng Ru, Paolo Boffetta. Dietary isoflavone intake and lung cancer risk: an analysis using data from the prostate, lung, colorectal, and ovary (PLCO) trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2585.