Associations between cigarette smoking, hormone therapy, and folate intake with incident colorectal cancer by TP53 protein expression level in a population-based cohort of older women.
Associations between cigarette smoking, hormone therapy, and folate intake with incident colorectal cancer by TP53 protein expression level in a population-based cohort of older women.
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DOI：
10.1158/1055-9965.epi-13-0780
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发表时间：
2014-02
期刊：
影响因子：
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通讯作者：
Limburg PJ
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文献类型：
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作者：
Tillmans LS;Vierkant RA;Wang AH;Jewel Samadder N;Lynch CF;Anderson KE;French AJ;Haile RW;Harnack LJ;Potter JD;Slager SL;Smyrk TC;Thibodeau SN;Cerhan JR;Limburg PJ
吸烟（CS），激素治疗（HT）和叶酸摄入量（FI）都被认为会影响结直肠癌（CRC）的风险，但潜在的分子机制仍不完全确定。TP53（p53）蛋白，由TP53肿瘤抑制基因编码，通常在CRC中突变，可以很容易地进行评估，以区分生物学上不同的CRC亚型。在这项前瞻性队列研究中，我们在爱荷华州妇女健康研究（IWHS）参与者中通过TP 53蛋白表达水平检查了CS、HT和FI相关的CRC风险。IWHS招募了41,836名随机选择的爱荷华州妇女，年龄在55 - 69岁之间，在1986年进入研究时持有有效的驾驶执照。在基线时评估自我报告的暴露变量。通过与爱荷华州癌症登记处的年度联系确定CRC事件病例。收集存档的石蜡包埋组织标本，并通过免疫组织化学评价TP53蛋白表达。拟合多变量考克斯回归模型，以估计CS、HT或FI与TP 53定义的CRC亚型之间相关性的相对风险（RR）和95%置信区间（CI）。492例大肠癌病例的环境暴露和蛋白表达数据：222例（45.1%）TP 53阴性，72例（14.6%）TP 53低，198例（40.2%）TP 53高。HT持续时间较长（> 5年）与TP 53高CRC呈负相关（RR = 0.50; 95%CI = 0.27 - 0.94）。未观察到其他统计学显著相关性。这些数据支持HT对老年女性结直肠癌发生TP53相关通路的可能异质性影响。
Cigarette smoking (CS), hormone therapy (HT) and folate intake (FI) are each thought to influence colorectal cancer (CRC) risk, but the underlying molecular mechanisms remain incompletely defined. The TP53 (p53) protein, encoded by the TP53 tumor suppressor gene that is commonly mutated in CRC, can be readily assessed to differentiate biologically distinct CRC subtypes. In this prospective cohort study, we examined CS, HT, and FI -associated CRC risks by TP53 protein expression level among Iowa Women's Health Study (IWHS) participants. The IWHS recruited 41,836 randomly selected Iowa women, ages 55-69 years, with a valid driver's license at study entry in 1986. Self-reported exposure variables were assessed at baseline. Incident CRC cases were ascertained by annual linkage with the Iowa Cancer Registry. Archived, paraffin-embedded tissue specimens were collected and evaluated for TP53 protein expression by immunohistochemistry. Multivariate Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs) for associations between CS, HT, or FI and TP53-defined CRC subtypes. Informative environmental exposure and protein expression data were available for 492 incident CRC cases: 222 (45.1%) TP53 negative, 72 (14.6%) TP53 low, and 198 (40.2%) TP53 high. Longer duration (> 5 years) of HT was inversely associated with TP53 high CRCs (RR = 0.50; 95% CI = 0.27-0.94). No other statistically significant associations were observed. These data support possible heterogeneous effects from HT on TP53-related pathways of colorectal carcinogenesis in older women.