Specific genes may signal aggressive prostate cancer (PCa) in African American men, according to researchers of a new study. The findings may partly explain ethnic disparities in PCa, which have been linked to both biologic and socioeconomic factors.

Investigators led by Kosj Yamoah, MD, of Thomas Jefferson University Hospital in Philadelphia, examined mRNA expression of 20 biomarkers associated with prostate cancer initiation and progression by ethnicity. The researchers matched 154 African American to 243 European American patients from 4 institutions based on the Cancer of the Prostate Risk Assessment postsurgical scores (CAPRA-S) of their tumors.   

According to results published in the Journal of Clinical Oncology, 6 biomarkers showed significant differential expression in black men: ERG, AMACR, SPINK1, NKX3-1, GOLM1, and androgen receptor. Risk of stage 3 PCa in African American patients was predicted by dysregulation of specific biomarkers (AMACR, ERG, FOXP1, and GSTP1) as well as by tumor suppressor mutations in NKX3-1 and RB1 that caused loss of function. In addition, dysregulation of GOLM1, SRD5A2, and MKi67 predicted 3-year biochemical recurrence and metastasis at 5 years. The researchers observed that more African American than European American patients (51 vs. 35%) had triple-negative PCa (i.e., absence or low levels of ERG, ETS, and SPINK1).

“Much of what we understand in terms of the genetics of prostate cancer to date has been based on clinical trials in Caucasian men,” Dr. Yamoah explained in a news release. “However, the data here suggest that a subset of African American men may have a type of prostate cancer that arises from molecular pathways that are distinctly different from those of European American men.”

African American patients with this biomarker signature may have better survival if they are treated with a different approach than standard of care, Dr. Yamoah suggested. The biomarkers need to be validated and refined in further studies involving larger groups of patients.

1. Yamoah, K; Johnson, MH; Choeurng, V; et al. Journal of Clinical Oncology; doi: 10.1200/JCO.2014.59.8912.
2. Thomas Jefferson University news release, July 21, 2015.

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(HealthDay News) -- Survivors of childhood cancer have an increased long-term risk of intestinal obstruction requiring surgery (IOS), according to a study published online in the Journal of Clinical Oncology.

Arin L. Madenci, M.D., M.P.H., from Boston Children's Hospital and Harvard Medical School, and colleagues assessed IOS occurring 5 or more years after cancer diagnosis. Data were included for 12,316 five-year survivors in the Childhood Cancer Survivor Study (2,002 with and 10,314 without abdominopelvic tumors) and 4,023 sibling participants.

The researchers found that 165 survivors (median age at IOS, 19 years; median time from diagnosis, 13 years) and 14 siblings reported late IOS. At 35 years, the cumulative incidence of late IOS was 5.8, 1.0, and 0.3% among survivors with abdominopelvic tumors, survivors without abdominopelvic tumors, and siblings, respectively. After adjustment for confounding variables, the rate of late IOS was increased with abdominopelvic tumor (adjusted rate ratio [aRR], 3.6; P < 0.001) and abdominal/pelvic radiotherapy within 5 years of cancer diagnosis (aRR, 2.4; P < 0.001). After adjustment for the same variables, developing late IOS correlated with increased subsequent mortality among survivors (aRR, 1.8: P = 0.016).

"The long-term risk of IOS and its association with subsequent mortality underscore the need to promote awareness of this complication among patients and providers," the authors write.

Several authors disclosed financial ties to the pharmaceutical industry.

Source

1. Madenci, AL; Fisher, S; Diller, LR; et al. Journal of Clinical Oncology, August 10, 2015; doi: 10.1200/JCO.2015.61.5070.

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