Gohlke Jie H, Lloyd Stacy M, Basu Sumanta, Putluri Vasanta, Vareed Shaiju K, Rasaily Uttam, Piyarathna Danthasinghe Waduge Badrajee, Fuentes Hunter, Rajendiran Thekkelnaycke M, Dorsey Tiffany H, Ambati Chandrashekar R, Sonavane Rajni, Karanam Balasubramanyam, Bhowmik Salil Kumar, Kittles Rick, Ambs Stefan, Mims Martha Pritchett, Ittmann Michael, Jones Jeffrey A, Palapattu Ganesh, Putluri Nagireddy, Michailidis George, Sreekumar Arun
JNCI Cancer Spectr. 2019 Apr 25;3(2):pkz019. doi: 10.1093/jncics/pkz019. eCollection 2019 Jun.
African American (AA) men have a 60% higher incidence and two times greater risk of dying of prostate cancer (PCa) than European American men, yet there is limited insight into the molecular mechanisms driving this difference. To our knowledge, metabolic alterations, a cancer-associated hallmark, have not been reported in AA PCa, despite their importance in tumor biology. Therefore, we measured 190 metabolites across ancestry-verified AA PCa/benign adjacent tissue pairs (n = 33 each) and identified alterations in the methionine-homocysteine pathway utilizing two-sided statistical tests for all comparisons. Consistent with this finding, methionine and homocysteine were elevated in plasma from AA PCa patients using case-control (AA PCa vs AA control, methionine: = .0007 and homocysteine: < .0001), biopsy cohorts (AA biopsy positive vs AA biopsy negative, methionine: = .0002 and homocysteine: < .0001), and race assignments based on either self-report (AA PCa vs European American PCa, methionine: = .001, homocysteine: < .0001) or West African ancestry (upper tertile vs middle tertile, homocysteine: < .0001; upper tertile vs low tertile, homocysteine: = .002). These findings demonstrate reprogrammed metabolism in AA PCa patients and provide a potential biological basis for PCa disparities.
非裔美国（AA）男性患前列腺癌（PCa）的发病率比欧美男性高60%，死于前列腺癌的风险是欧美男性的两倍，但对于导致这种差异的分子机制，人们了解有限。据我们所知，代谢改变作为一种癌症相关特征，在AA前列腺癌中尚未见报道，尽管其在肿瘤生物学中很重要。因此，我们在经过血统验证的AA前列腺癌/良性相邻组织对（每组n = 33）中测量了190种代谢物，并通过双侧统计检验对所有比较进行分析，确定了甲硫氨酸-同型半胱氨酸途径的改变。与此发现一致，在病例对照研究（AA前列腺癌患者与AA对照，甲硫氨酸：P = 0.0007，同型半胱氨酸：P < 0.0001）、活检队列（AA活检阳性与AA活检阴性，甲硫氨酸：P = 0.0002，同型半胱氨酸：P < 0.0001）以及基于自我报告（AA前列腺癌患者与欧美前列腺癌患者，甲硫氨酸：P = 0.001，同型半胱氨酸：P < 0.0001）或西非血统（上三分位数与中三分位数，同型半胱氨酸：P < 0.0001；上三分位数与下三分位数，同型半胱氨酸：P = 0.002）的种族分组中，AA前列腺癌患者血浆中的甲硫氨酸和同型半胱氨酸水平升高。这些发现证明了AA前列腺癌患者的代谢重编程，并为前列腺癌差异提供了潜在的生物学基础。
