Urinary Thromboxane B2 May Be Marker of Aggressive Prostate Cancer in Black Men

By Reuters Staff

July 26, 2021

NEW YORK (Reuters Health) - Upregulation of urinary thromboxane B2 may be a new marker of aggressive prostate cancer in African American men, a group that bears a disproportionately high burden of lethal prostate cancer.

Thromboxane A2 (TXA2) is a platelet- and cyclooxygenase-derived eicosanoid that has been linked to metastasis. Dr. Stefan Ambs and colleagues with the National Cancer Institute investigated the role of TXA2 in the development of lethal prostate cancer in African American (AA) and European American (EA) men.

Using mass-spectrometry, they measured urinary 11-dehydrothromboxane B2 (TXB2), a stable metabolite of TXA2, in 977 men with prostate cancer (490 AA and 487 EA) and 1,022 controls (479 AA and 543 EA). During a median follow-up of 8.4 years, 246 men with prostate cancer died.

There was a statistically significant association between high TXB2 and having prostate cancer among AA men (odds ratio, 1.50) but not EA men (OR, 1.07), the researchers report in the Journal of the National Cancer Institute.

High TXB2 was associated with significantly increased all-cause mortality in AA men (hazard ratio, 1.59) but not in EA men (HR 1.11).

The results showed a "distinct" association of upregulated TXB2 with lethal prostate cancer in AA men, the researchers write.

High TXB2 was also associated with higher prostate-cancer-specific mortality in AA men (HR, 4.74) but not in EA men (HR, 1.12).

The association between high TXB2 and all-cause mortality remained significant only in AA men who did not use aspirin but not in aspirin users, the researchers note.

"Our observations suggest that aspirin may reduce all-cause mortality by decreasing TXA2/TXB2 levels in AA patients with an otherwise upregulated pro-metastatic COX1/TXA2 pathway," they say.

"Our findings further corroborate the hypothesis that a systemic low-grade inflammation is prevalent in AA men with prostate cancer and these elevated inflammatory processes are contributing to adverse outcomes for this population," they add.

A limitation of the study is the retrospective, case-control study design, "so it remains unknown if elevated TXA2 is a risk factor for prostate cancer development," they note. It's also unclear why AA men with prostate cancer have higher TXB2 levels than EA men.

Also data on aspirin use were self-reported. "However, our findings that aspirin use may reduce TXA2/TXB2 levels is very much in agreement with the published literature providing strong support of the correctness of the self-reported aspirin use data," the team says. "Lack of dose information for aspirin use prevents us from making any conclusions as to what dose is required to inhibit TXA2."

Summing up, Dr. Ambs and colleagues say their work "identifies a novel association between high urinary TXB2 and aggressive prostate cancer as well as adverse survival outcomes for AA men. These observations need further validation, but they are consistent with our previous findings of a prevalent immune-inflammation signature and an inverse association of aspirin use with lethal prostate cancer in these patients. Our study highlights the potential benefit of aspirin for prevention of lethal prostate cancer in this high-risk group of men through inhibition of TXA2 synthesis."

The study had no commercial funding and the authors have no relevant disclosures.

SOURCE: https://bit.ly/3rtij30 Journal of the National Cancer Institute, online July 15, 2021.

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