Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2021 Aug;125(4):569-575.
doi: 10.1038/s41416-021-01410-0. Epub 2021 May 18.

PALB2 mutations and prostate cancer risk and survival

Dominika Wokołorczyk  1 , Wojciech Kluźniak  1 , Klaudia Stempa  1 , Bogna Rusak  1 , Tomasz Huzarski  1   2 , Jacek Gronwald  1 , Katarzyna Gliniewicz  1 , Aniruddh Kashyap  1 , Sylwia Morawska  1 , Tadeusz Dębniak  1 , Anna Jakubowska  1   3 , Marek Szwiec  4 , Paweł Domagała  5 , Jan Lubiński  1 , Steven A Narod  6   7 , Mohammad R Akbari  6   7 , Cezary Cybulski  8 ; Polish Hereditary Prostate Cancer Consortium
Collaborators, Affiliations
Multicenter Study

PALB2 mutations and prostate cancer risk and survival

Dominika Wokołorczyk et al. Br J Cancer. 2021 Aug.

Abstract

Background: The objective of this study was to establish the contribution of PALB2 mutations to prostate cancer risk and to estimate survival among PALB2 carriers.

Methods: We genotyped 5472 unselected men with prostate cancer and 8016 controls for two Polish founder variants of PALB2 (c.509_510delGA and c.172_175delTTGT). In patients with prostate cancer, the survival of carriers of a PALB2 mutation was compared to that of non-carriers.

Results: A PALB2 mutation was found in 0.29% of cases and 0.21% of controls (odds ratio (OR) = 1.38; 95% confidence interval (CI) 0.70-2.73; p = 0.45). PALB2 mutation carriers were more commonly diagnosed with aggressive cancers of high (8-10) Gleason score than non-carriers (64.3 vs 18.1%, p < 0.0001). The OR for high-grade prostate cancer was 8.05 (95% CI 3.57-18.15, p < 0.0001). After a median follow-up of 102 months, the age-adjusted hazard ratio for all-cause mortality associated with a PALB2 mutation was 2.52 (95% CI 1.40-4.54; p = 0.0023). The actuarial 5-year survival was 42% for PALB2 carriers and was 72% for non-carriers (p = 0.006).

Conclusion: In Poland, PALB2 mutations predispose to an aggressive and lethal form of prostate cancer.

PubMed Disclaimer

Conflict of interest statement

S.N. is an editorial board member for the British Journal of Cancer. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Kaplan–Meier curves of prostate cancer patients with a PALB2 mutation, compared with mutation-negative prostate cancer patients (non-carriers).
PALB2 mutation non-carriers—men with prostate cancer who tested negative for PALB2 c.509_510delGA and c.172_175delTTGT mutations. PALB2 mutation carriers—men with prostate cancer who tested positive for PALB2 c.509_510delGA or c.172_175delTTGT mutation.
Fig. 2
Fig. 2. Loss of heterozygosity (LOH) analysis in prostate cancer tissues and normal tissues from four carriers of a PALB2 mutation; retention of the wild-type PALB2 allele is seen in two tumours; two tumours probably have loss of the wild-type PALB2 allele (best shown by asterisks).
PALB2 mutations are indicated by an arrow (↓). On chromatograms green peaks correspond to nucleotide A, red peaks to nucleotide T, black peaks to nucleotide G, and blue peaks to nucleotide C.
See this image and copyright information in PMC

References

    1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer. 2015;136:359–386. doi: 10.1002/ijc.29210. - DOI - PubMed
    1. Carter BS, Beaty TH, Steinberg GD, Childs B, Walsh PC. Mendelian inheritance of familial prostate cancer. Proc. Natl Acad. Sci. USA. 1992;89:3367–3371. doi: 10.1073/pnas.89.8.3367. - DOI - PMC - PubMed
    1. Mucci LA, Hjelmborg JB, Harris JR, Czene K, Havelick DJ, Scheike T, et al. Familial risk and heritability of cancer among twins in Nordic countries. JAMA. 2016;315:68–76. doi: 10.1001/jama.2015.17703. - DOI - PMC - PubMed
    1. Schumacher FR, Al Olama AA, Berndt SI, Benlloch S, Ahmed M, Saunders EJ, et al. Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci. Nat. Genet. 2018;50:928–936. doi: 10.1038/s41588-018-0142-8. - DOI - PMC - PubMed
    1. Ewing CM, Ray AM, Lange EM, Zuhlke KA, Robbins CM, Tembe WD, et al. Germline mutations in HOXB13 and prostate-cancer risk. N. Engl. J. Med. 2012;366:141–149. doi: 10.1056/NEJMoa1110000. - DOI - PMC - PubMed

Publication types

Substances