Abstract：
BACKGROUND: Higher coffee intake has been associated with reduced risk of prostate cancer, particularly aggressive forms. The activation of the PI3K signaling pathway plays an important role in prostate carcinogenesis.
OBJECTIVE: To evaluate associations between pre-diagnostic coffee intake and a PI3K activation score, the expression/presence of PI3K regulators, and downstream effectors in tumor tissue from men with prostate cancer in the Health Professionals Follow-up Study, a prospective cohort study conducted in the US.
METHODS: A case-only study design was applied. Coffee intake was assessed using validated food frequency questionnaires completed in 1986 and every four years thereafter until prostate cancer diagnosis.
METHODS: Study participants comprised 1,242 men diagnosed with prostate cancer from 1986 to 2009 and with tumor markers assessed from tissue microarrays constructed from tumor specimens.
METHODS: The outcomes include the PI3K activation score; expression of insulin receptor and IGF1 receptor; angiogenesis markers; and presence of the tumor suppressor PTEN, chronic and acute inflammation, simple atrophy, and post-atrophic hyperplasia.
METHODS: Multivariable linear or logistic regression was conducted to estimate associations between coffee intake and tumor marker expression/presence.
RESULTS: Among coffee drinkers (86.6% of the population), median (25th-75th) coffee intake was 2 (1-3) cups/day. The associations between coffee consumption and the tumor markers of interest were generally weak with modest precision. When comparing men who drank >3 cups/day of coffee with nondrinkers, the absolute percent difference in the PI3K activation score and angiogenesis markers ranged from 0.6% to 3.6%. The odds ratios for PTEN loss, IGF1 receptor and insulin receptor expression, and presence of chronic and acute inflammation, simple atrophy, and post-atrophic hyperplasia also were not statistically significant, were imprecise, and ranged from 0.82 to 1.58.
CONCLUSIONS: Coffee intake was not observed to be associated with PI3K activation, related regulators, and several effectors in prostate tumor tissue. Studies exploring alternative pathways or earlier steps in carcinogenesis are needed to investigate the underlying mechanisms of the coffee and prostate cancer association.
OBJECTIVE: To evaluate associations between pre-diagnostic coffee intake and a PI3K activation score, the expression/presence of PI3K regulators, and downstream effectors in tumor tissue from men with prostate cancer in the Health Professionals Follow-up Study, a prospective cohort study conducted in the US.
METHODS: A case-only study design was applied. Coffee intake was assessed using validated food frequency questionnaires completed in 1986 and every four years thereafter until prostate cancer diagnosis.
METHODS: Study participants comprised 1,242 men diagnosed with prostate cancer from 1986 to 2009 and with tumor markers assessed from tissue microarrays constructed from tumor specimens.
METHODS: The outcomes include the PI3K activation score; expression of insulin receptor and IGF1 receptor; angiogenesis markers; and presence of the tumor suppressor PTEN, chronic and acute inflammation, simple atrophy, and post-atrophic hyperplasia.
METHODS: Multivariable linear or logistic regression was conducted to estimate associations between coffee intake and tumor marker expression/presence.
RESULTS: Among coffee drinkers (86.6% of the population), median (25th-75th) coffee intake was 2 (1-3) cups/day. The associations between coffee consumption and the tumor markers of interest were generally weak with modest precision. When comparing men who drank >3 cups/day of coffee with nondrinkers, the absolute percent difference in the PI3K activation score and angiogenesis markers ranged from 0.6% to 3.6%. The odds ratios for PTEN loss, IGF1 receptor and insulin receptor expression, and presence of chronic and acute inflammation, simple atrophy, and post-atrophic hyperplasia also were not statistically significant, were imprecise, and ranged from 0.82 to 1.58.
CONCLUSIONS: Coffee intake was not observed to be associated with PI3K activation, related regulators, and several effectors in prostate tumor tissue. Studies exploring alternative pathways or earlier steps in carcinogenesis are needed to investigate the underlying mechanisms of the coffee and prostate cancer association.
摘要：
背景：较高的咖啡摄入量与前列腺癌的风险降低有关，特别是侵略性的形式。PI3K信号通路的激活在前列腺癌的发生中起重要作用。
目的：评估诊断前咖啡摄入量与PI3K激活评分之间的关联，PI3K调节剂的表达/存在，在健康专业人员随访研究中，前列腺癌男性肿瘤组织中的下游效应物，一项在美国进行的前瞻性队列研究.
方法：采用仅病例研究设计。使用1986年完成的经过验证的食物频率问卷评估咖啡摄入量，此后每四年进行一次，直到前列腺癌诊断。
方法：研究参与者包括1986年至2009年诊断为前列腺癌的1,242名男性，并从肿瘤标本构建的组织微阵列评估肿瘤标志物。
方法：结果包括PI3K激活评分；胰岛素受体和IGF1受体的表达；血管生成标志物；肿瘤抑制因子PTEN的存在，慢性和急性炎症，单纯性萎缩,和萎缩性增生后。
方法：进行多变量线性或逻辑回归以估计咖啡摄入量与肿瘤标志物表达/存在之间的关联。
结果：在喝咖啡的人中（占人口的86.6％），中位数（第25-75位）咖啡摄入量为2（1-3）杯/天。咖啡消耗与感兴趣的肿瘤标记物之间的关联通常较弱，精度适中。当比较每天喝咖啡>3杯的男人和不喝酒的男人时，PI3K激活评分和血管生成标志物的绝对百分比差异为0.6%~3.6%.PTEN损失的赔率比，IGF1受体和胰岛素受体表达，以及慢性和急性炎症的存在，单纯性萎缩,萎缩性增生也没有统计学意义，不精确，范围从0.82到1.58。
结论：未观察到咖啡摄入与PI3K激活相关，相关监管机构，和前列腺肿瘤组织中的几个效应物。需要探索癌症发生中的替代途径或更早步骤的研究来研究咖啡和前列腺癌关联的潜在机制。
目的：评估诊断前咖啡摄入量与PI3K激活评分之间的关联，PI3K调节剂的表达/存在，在健康专业人员随访研究中，前列腺癌男性肿瘤组织中的下游效应物，一项在美国进行的前瞻性队列研究.
方法：采用仅病例研究设计。使用1986年完成的经过验证的食物频率问卷评估咖啡摄入量，此后每四年进行一次，直到前列腺癌诊断。
方法：研究参与者包括1986年至2009年诊断为前列腺癌的1,242名男性，并从肿瘤标本构建的组织微阵列评估肿瘤标志物。
方法：结果包括PI3K激活评分；胰岛素受体和IGF1受体的表达；血管生成标志物；肿瘤抑制因子PTEN的存在，慢性和急性炎症，单纯性萎缩,和萎缩性增生后。
方法：进行多变量线性或逻辑回归以估计咖啡摄入量与肿瘤标志物表达/存在之间的关联。
结果：在喝咖啡的人中（占人口的86.6％），中位数（第25-75位）咖啡摄入量为2（1-3）杯/天。咖啡消耗与感兴趣的肿瘤标记物之间的关联通常较弱，精度适中。当比较每天喝咖啡>3杯的男人和不喝酒的男人时，PI3K激活评分和血管生成标志物的绝对百分比差异为0.6%~3.6%.PTEN损失的赔率比，IGF1受体和胰岛素受体表达，以及慢性和急性炎症的存在，单纯性萎缩,萎缩性增生也没有统计学意义，不精确，范围从0.82到1.58。
结论：未观察到咖啡摄入与PI3K激活相关，相关监管机构，和前列腺肿瘤组织中的几个效应物。需要探索癌症发生中的替代途径或更早步骤的研究来研究咖啡和前列腺癌关联的潜在机制。
