Cancer Res Treat.  2019 Jul;51(3):1180-1187. 10.4143/crt.2018.532.

Inherited NBN Mutations and Prostate Cancer Risk and Survival

• Rusak B
• Kluźniak
• WokoÅ‚orczykv D
• Stempa K
• Kashyap A
• Gronwald J
• Huzarski T
• DÄ™bniak T
• Jakubowska A
• Masojć B
• Akbari MR
• Narodv SA
• LubiÅ„ski
• Cybulski C
• The Polish Hereditary Prostate Cancer Consortium

• KMID: 2454309
• DOI: http://doi.org/10.4143/crt.2018.532

Abstract

PURPOSE
The purpose of this study was to establish the contribution of four founder alleles of NBN to prostate cancer risk and cancer survival.
MATERIALS AND METHODS
Five thousand one hundred eighty-nine men with prostate cancer and 6,152 controls were genotyped for four recurrent variants of NBN (657del5, R215W, I171V, and E185Q).
RESULTS
The NBN 657del5 mutation was detected in 74 of 5,189 unselected cases and in 35 of 6,152 controls (odds ratio [OR], 2.5; p < 0.001). In carriers of 657del5 deletion, the cancer risk was restricted to men with the GG genotype of the E185Q variant of the same gene. Among men with the GG genotype, the OR associated with 657del5 was 4.4 (95% confidence interval [CI], 2.4 to 8.0). Among men with other E185Q genotypes, the OR associated with 657del5 was 1.4 (95% CI, 0.8 to 2.4) and the interaction was significant (homogeneity p=0.006). After a median follow-up of 109 months, mortality was worse for 657del5 mutation carriers than for non-carriers (hazard ratio [HR], 1.6; p=0.001). The adverse effect of 657del5 on survival was only seen on the background of the GG genotype of E185Q (HR, 1.9; p=0.0004).
CONCLUSION
The NBN 657del5 mutation predisposes to poor prognosis prostate cancer. The pathogenicity of this mutation, with regards to both prostate cancer risk and survival, is modified by a missense variant of the same gene (E185Q).

Keyword

NBN; NBS1; Mutation; Aggressive prostate cancer; Survival

MeSH Terms

Alleles
Follow-Up Studies
Genotype
Humans
Male
Mortality
Prognosis
Prostate*
Prostatic Neoplasms*
Virulence

Figure

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  Fig. 1. Kaplan-Meier curves of prostate cancer patients with 657del5 mutation in NBN, compared with prostate cancer patients without 657del5 variant (non-carriers). HR, hazard ratio.

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  Fig. 2. Kaplan-Meier curves of prostate cancer patients with a 657del5 mutation in NBN and non-carriers: on the GG genotype background of E185Q (A); on the non-GG (GC and CC) genotype background of E185Q (B).

Reference

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