Graff Rebecca E, Pettersson Andreas, Lis Rosina T, Ahearn Thomas U, Markt Sarah C, Wilson Kathryn M, Rider Jennifer R, Fiorentino Michelangelo, Finn Stephen, Kenfield Stacey A, Loda Massimo, Giovannucci Edward L, Rosner Bernard, Mucci Lorelei A
Departments of Epidemiology, Departments ofEpidemiology and Biostatistics and
Departments of Epidemiology, Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden;
Am J Clin Nutr. 2016 Mar;103(3):851-60. doi: 10.3945/ajcn.115.118703. Epub 2016 Jan 27.
There is limited evidence that supports etiologically distinct molecular subtypes of prostate cancer, the identification of which may improve prevention. Given their antioxidant properties, we hypothesized that lycopene and tomato sauce may be especially protective against diseases harboring the common gene fusion transmembrane protease, serine 2 (TMPRSS2):v-ets avian erythroblastosis virus E26 oncogene homolog (ERG).
We aimed to examine associations between estimated lycopene and tomato sauce intake and the risk of prostate cancer defined by ERG protein expression subtype.
Our study population consisted of a prospective cohort of 46,719 men from the Health Professionals Follow-Up Study. TMPRSS2:ERG was assessed by ERG immunohistochemistry on tumor tissue microarrays constructed from radical prostatectomy specimens. We used multivariable competing risk models to calculate HRs and 95% CIs for the risk of ERG-positive and, separately, ERG-negative disease. We implemented inverse probability weighting to account for evaluating ERG status only in surgically treated cases.
During 23 y of follow-up, 5543 men were diagnosed with prostate cancer, among whom 884 were assayed for ERG (426 ERG-positive). With inclusion of only the latter cases, increasing cumulative average tomato sauce intake was associated with a decreased risk of prostate cancer overall (≥2 servings/wk compared with <1 serving/mo; multivariable HR: 0.70; 95% CI: 0.52, 0.95; P-trend = 0.002). With respect to molecular subtypes, cumulative average tomato sauce intake was associated with a decreased risk of ERG-positive disease (HR: 0.54; 95% CI: 0.37, 0.81; P-trend = 0.004) but not with ERG-negative disease (HR: 0.96; 95% CI: 0.62, 1.50; P-trend = 0.10) (P-heterogeneity = 0.04). Increasing quintiles of lycopene intake were associated with a decreased risk of both subtypes (P-heterogeneity = 0.79). Inverse probability weighting did not materially change the results.
Our results lend some support to the hypothesis that prostate cancers that harbor TMPRSS2:ERG may be etiologically distinct from fusion-negative cancers. In particular, tomato sauce consumption may play a role in reducing TMPRSS2:ERG-positive disease.
支持前列腺癌病因学上不同分子亚型的证据有限，而识别这些亚型可能有助于改善预防措施。鉴于番茄红素和番茄酱具有抗氧化特性，我们推测它们可能对携带常见基因融合跨膜蛋白酶丝氨酸2（TMPRSS2）：禽成红细胞增多症病毒E26癌基因同源物（ERG）的疾病具有特别的保护作用。
我们旨在研究估计的番茄红素和番茄酱摄入量与由ERG蛋白表达亚型定义的前列腺癌风险之间的关联。
我们的研究人群包括来自健康专业人员随访研究的46719名男性的前瞻性队列。通过对从根治性前列腺切除标本构建的肿瘤组织微阵列进行ERG免疫组织化学评估TMPRSS2：ERG。我们使用多变量竞争风险模型来计算ERG阳性和ERG阴性疾病风险的HR及95%CI。我们采用逆概率加权法以仅在接受手术治疗的病例中评估ERG状态。
在23年的随访期间，5543名男性被诊断为前列腺癌，其中884人接受了ERG检测（426人ERG阳性）。仅纳入后一组病例，累计平均番茄酱摄入量增加与总体前列腺癌风险降低相关（每周≥2份与每月<1份相比；多变量HR：0.70；95%CI：0.52，0.95；P趋势 = 0.002）。就分子亚型而言，累计平均番茄酱摄入量与ERG阳性疾病风险降低相关（HR：0.54；95%CI：0.37，0.81；P趋势 = 0.004）但与ERG阴性疾病无关（HR：0.96；95%CI：0.62，1.50；P趋势 = 0.10）（P异质性 = 0.04）。番茄红素摄入量增加的五分位数与两种亚型疾病风险降低均相关（P异质性 = 0.79）。逆概率加权并未实质性改变结果。
我们的数据为以下假设提供了一些支持，即携带TMPRSS2：ERG的前列腺癌在病因上可能与融合阴性癌症不同。特别是，食用番茄酱可能在降低TMPRSS2：ERG阳性疾病方面发挥作用。
