Yang G, Shu XO, Li HL, et al. Prediagnosis soy food consumption and lung cancer survival in women. J Clin Oncol. 2013;31(13) [Epub ahead of print]
Longitudinal cohort study using data from the Shanghai Women’s Health Study
Participants were those that developed lung cancer while enrolled in the Shanghai Women’s Health Study (SWHS). This ongoing study recruited 74,941 adult Chinese women from 7 communities in Shanghai from 1997 to 2000. It continues to track the incidence of various cancers in these women. In the current study, 469 women were found to have incident lung cancer. Due to lack of sufficient information on 25 of them, a total of 444 were used for analysis. Of these, 301 had sufficient information to give statistical analysis using tumor stage and treatment as variables. The average age at diagnosis was 66.3 years. Ninety-two percent of participants were “never” smokers.
The primary outcome measure was overall survival. No secondary outcomes were measured.
There were 318 total deaths in the 444 women with lung cancer. Of these, 94.7% were attributed directly to lung cancer and 5.3% were due to other causes. Stage of disease at initial diagnosis had the greatest impact on survival. Soy intake and isoflavone intake was assessed before enrollment in SWHS through food frequency questionnaire. The 50th percentile of intake was used as the reference for hazard ratio assessment. Based on dry weight, median intake levels of soy by percentile were as follows: 10th=6.3 grams/d; 30th=11.5 grams/d; 50th=16 grams/d; 70th=21.4 grams/d; 90th=31.4 grams/d. Risk of death decreased with increased soy intake up to the 70th percentile, where there was a leveling off of the effect. Hazard ratios for death for all 444 participants by percentile were as follows: 10th HR=1.42; 30th HR=1.15; 50th HR=1.0; 70th HR=0.92; 90th HR=0.93. When only the 301 participants with sufficient information on tumor stage and treatment were analyzed compared to the median intake of soy (50th percentile) the hazard ratios for the 10th, 30th, 70th and 90th percentiles were 1.81 (95% CI: 1.26–2.59), 1.25 (95% CI: 1.09–1.42), 0.88 (95% CI: 0.80–0.97), and 0.89 (95% CI: 0.68–1.16) respectively. P for overall significance was 0.004. This association was consistent and more pronounced in never smokers, with hazard ratios for the 10th, 30th 70th, and 90th percentiles of 2.40 (95% CI: 1.47–3.91), 1.42 (95% CI: 1.17–1.72), 0.85 (95% CI: 0.76–0.96), and 0.92 (95% CI: 0.66–1.28) respectively, with a P value of 0.002.
In the current study, the amount of soy consumed prediagnosis was associated with decreased risk of death from lung cancer. It is essential to note that soy intake was assessed before—not after—diagnosis, so we do not know whether soy consumption would confer benefit if begun after diagnosis. That said, if one assumes that the eating habits of the participating women did not change dramatically during the trial, this study appears to be the first to suggest overall survival from lung cancer is improved with soy consumption.
The authors of the current study have published prior analysis of data from the SWHS that showed an associated decrease in the incidence of lung cancer in those with higher soy consumption levels, suggesting some protection from carcinogenic processes. The results were statistically significant (P=0.004) with a hazard ratio of 0.63 when comparing the highest versus lowest intakes.1 In the same publication, a meta-analysis of 7 studies on soy/isoflavone intake and lung cancer in non-smokers found a relative risk of 0.59 (95% CI: 0.49, 0.71) for the highest versus the lowest categories of soy intake.
Several other studies have suggested a decreased risk of incident lung cancer with higher soy and/or isoflavone consumption. In a Japanese cohort of 36,177 men and 40,484 women aged 45–74 years, there was less incident lung cancer in both genders with higher isoflavone intake, but only in those who never smoked.2 In a meta-analysis of 8 case-control and 3 prospective cohort studies, there was again an inverse correlation between soy consumption and incident lung cancer (relative risk of 0.77, 95% CI: 0.65, 0.92).3 In keeping with the Japanese cohort, the meta-analysis found the effects were greater in non-smokers (RR: 0.62; 95% CI: 0.51, 0.76).
Adding whole soy foods to one's diet is an easy and inexpensive means of adding to the chemoprotective effects of a diet high in plant-based foods.
While most of the data on soy consumption and lung cancer is from Asia, one large study was conducted in the United States. It was a case control study with participants enrolling from 1995–2003. This study looked at various phytoestrogen classes, including phytosterols, coumestans, isoflavones, and lignans. Overall, they found there was an associated decreased risk of incident lung cancer with increasing intake of phytoestrogens in both genders. This study, published in the Journal of the American Medical Association, suggested that all classes of phytoestrogens have some protective effect, with isoflavones having the greatest reduction in risk, especially in men.4
Unlike breast cancer, where there is a linear relationship between endogenous and ingested estrogens and increased cancer risk, the relationship of estrogens in lung cancer seems to be more complex. Data from the National Institutes of Health and American Association of Retired Persons (NIH-AARP) study suggest that women with a late menarche may have decreased risk of lung cancer, while those undergoing early menopause (natural or surgical) have increased risk.5 To add to the complexity, the increased risk in those with early menopause was exaggerated in smokers.
Hormonal mediation of lung cancer has been appreciated for some time; evidence suggests that estrogens promote the progression of lung cancer and that hormone replacement therapy (HRT) is linked to poorer outcomes.6 The Women’s Health Initiative found an increased risk of death due to lung cancer in women taking estrogen/progestin replacement therapy.7 There is conflicting data suggesting that HRT usage is associated with reduced risk of incident lung cancer,8,9 but appreciation is growing for the variability of estrogen metabolism between individuals and ethnicities.
A Chinese case-control study sought to further define what metabolic pathways may mediate the effects of estrogen on lung cancer, and whether the effects were different in smokers versus non-smokers.10 In their study of 708 female lung cancer patients and 1,578 matched controls, they found that in non-smokers parity and menstrual cycle length (≥30 days vs <30 days) were inversely associated with lung cancer risk. Of interest, there was a distinct increase in lung cancer risk in non-smokers barring a point mutation in one of the COMT enzymes involved in estrogen metabolism. The authors concluded that there is a definite influence on lung cancer risk that is mediated by estrogen and its metabolites in non-smokers.
In all of these studies, the dominant histology of lung cancer is adenocarcinoma, which is responsible for approximately 40% of all non-small cell lung cancers. While adenocarcinoma is linked to smoking, it is also the most common type of lung cancer arising in non-smokers. Of late, the diagnosis of lung cancer in non-smokers is being considered as a separate entity with unique genomic features.11 The most well-studied etiological agents in adenocarcinoma of the lung in non-smokers are radon, air pollution, and second-hand smoke. Certainly, in our patients with exposures to airborne toxins or likely carcinogens (ie, diesel fumes), there is good reason to consider suggesting soy be included in their diet.
From a practical point of view, there is one hurdle in recommending soy for our patients at greater risk for lung cancer. Soy has become quite controversial in the lay media, with various health and wellness outlets advising against its consumption completely. This is largely due to concerns regarding the use of genetically modified (GMO) crops in the United States. While the topic of genetically modified soy is too complex to cover here, the use of organic sources would mitigate any risk substantially.
The epidemiological data consistently suggest a role for soy/isoflavones in protecting against lung cancer, and the current study suggests it may affect overall survival in those with lung cancer as well. Adding whole soy foods to one’s diet is an easy and inexpensive means of adding to the chemoprotective effects of a diet high in plant-based foods.
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- Yang G, Shu XO, Chow W-H, et al. Soy food intake and risk of lung cancer: evidence from the shanghai women's health study and a meta-analysis. Am J Epidemiol. 2012;176(10):846-855.
- Shimazu T, Inoue M, Sasazuki S, et al. Isoflavone intake and risk of lung cancer: a prospective cohort study in Japan. Am J Clin Nutr. 2010;91(3):722-728.
- Yang WS, Va P, Wong M-Y, Zhang H-L, Xiang Y-B. Soy intake is associated with lower lung cancer risk: results from a meta-analysis of epidemiologic studies. Am J Clin Nutr. 2011;94(6):1575-1583.
- Schabath MB, Hernandez LM, Wu X, Pillow PC, Spitz MR. Dietary phytoestrogens and lung cancer risk. JAMA. 2005; 294(12):1493-1504.
- Brinton LA, Gierach GL, Andaya A, et al. Reproductive and hormonal factors and lung cancer risk in the NIH-AARP diet and health study cohort. Cancer Epidemiol Biomarkers Prev. 2011;20(5): 900-911.
- Ganti AK, Sahmoun AE, Panwalkar AW, Tendulkar KK, Potti A. Hormone replacement therapy is associated with decreased survival in women with lung cancer. J Clin Oncol. 2006;24(1):59-63.
- Chlebowski RT, Schwartz AG, Wakelee H, et al. Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial. Lancet. 2009;374(9697):1243-1251.
- Chen K-Y, Hsiao C-F, Chang G-C, et al. Hormone replacement therapy and lung cancer risk in Chinese. Cancer. 2007;110(8):1768-1775.
- Schabath MB, Wu X, Vassilopoulou-Sellin R, Vaporciyan AA, Spitz MR. Hormone replacement therapy and lung cancer risk: a case-control analysis. Clin Cancer Res. 2004;10(1):113-123.
- Lim W-Y, Chen Y, Chuah KL, et al. Female reproductive factors, gene polymorphisms in the estrogen metabolism pathway, and risk of lung cancer in chinese women. Am J Epidemiol. 2012;175(6):492-503.
- Yang P. Lung cancer in never smokers. Seminars in respiratory and critical care medicine. NIH Public Access, 2011, p. 10.