Yale School of Public Health, Yale University School of Medicine, New Haven, CT 06520, United States.
Cancer Epidemiol. 2009 Oct;33(3-4):249-56. doi: 10.1016/j.canep.2009.08.004. Epub 2009 Sep 12.
Glutathione S-transferase (GST) enzymes are involved in electrophile detoxification. The authors investigated the association between GST genotype and survival in a racially diverse, population-based cohort of colorectal cancer (CRC) patients followed for a median of 9.6 years.
Interviews were conducted with 315 African-American and White CRC patients in Connecticut, 1987-1991. Tumor tissue (n=197) was later retrieved from hospital of diagnosis and assayed using multiplex PCR (GSTM1 and GSTT1) and PCR and RFLP analysis (GSTP1). Cox proportional hazards models provided adjusted hazard ratios (HR) and 95% confidence intervals (CI).
Individuals with Ile/Val or Val/Val GSTP1 genotypes had a decreased risk of death (multivariate adjusted HR=0.72, 95% CI: 0.48, 1.09) relative to those with wild type (Ile/Ile). Among those who received chemotherapy, this benefit was more pronounced (HR=0.35, 95% CI: 0.16, 0.79); the interaction of reduced function GSTP1 genotype and chemotherapy was significant (P=0.05). GSTM1 and GSTT1 genotype were not associated with survival. GSTM1, GSTT1, and GSTP1 genotype did not vary by race and did not contribute significantly to the survival disadvantage observed in African-Americans.
In summary, GSTP1 genotype may play a role in CRC survival in African-Americans and Whites, particularly among those who receive chemotherapy.
谷胱甘肽 S-转移酶（GST）酶参与亲电解毒。作者研究了 GST 基因型与种族多样化、基于人群的结直肠癌（CRC）患者生存的相关性，这些患者的中位随访时间为 9.6 年。
1987 年至 1991 年，对康涅狄格州的 315 名非裔美国人和白人 CRC 患者进行了访谈。随后从诊断医院获取肿瘤组织（n=197），并使用多重 PCR（GSTM1 和 GSTT1）和 PCR 和 RFLP 分析（GSTP1）进行检测。Cox 比例风险模型提供了调整后的危险比（HR）和 95%置信区间（CI）。
与野生型（Ile/Ile）相比，GSTP1 基因型为 Ile/Val 或 Val/Val 的个体死亡风险降低（多变量调整 HR=0.72，95%CI：0.48，1.09）。在接受化疗的患者中，这种益处更为明显（HR=0.35，95%CI：0.16，0.79）；功能降低的 GSTP1 基因型和化疗之间的相互作用具有统计学意义（P=0.05）。GSTM1 和 GSTT1 基因型与生存无关。GSTM1、GSTT1 和 GSTP1 基因型不因种族而异，也不能显著导致非裔美国人和白人观察到的生存劣势。
总之，GSTP1 基因型可能在非裔美国人和白人群体中的 CRC 生存中发挥作用，尤其是在接受化疗的患者中。
