PALB2 Linked to Increased Risk for Breast, Ovarian, and Pancreatic Cancer

By Christina Bennett, MS

Germline PALB2 pathogenic variants were associated with an increased risk for female breast cancer, male breast cancer, ovarian cancer, and pancreatic cancer, and these risks varied by age, according to data from an international study recently that was published in the Journal of Clinical Oncology.

The study included 524 families made up of 17,906 individuals from 21 countries. Eligible families had at least 1 family member with a PALB2 pathogenic variant. Families with a known BRCA1/BRCA2pathogenic variant were excluded.

PALB2 pathogenic variants were associated with an estimated 7-fold higher relative risk (RR) of female breast cancer (RR, 7.18; 95% CI, 5.82-8.85; P =6.5 × 10-76), which decreased with age, from a RR of 13.10 at age 25 years to 4.69 at age 75 years (P =2.0 × 10-3).  PALB2 pathogenic variants carried an absolute risk of 16.9% (95% CI, 13.3%-21.3%) of developing breast cancer by age 50 years and an absolute risk of 52.8% (95% CI, 43.7%-62.7%) of developing breast cancer by age 80 years.

PALB2 pathogenic variants were associated with an estimated nearly 3-fold higher RR of ovarian cancer (RR, 2.91; 95% CI, 1.40-6.04; P =4.1 × 10-3), which translated into an absolute risk of 0.6% (95% CI, 0.3%-1.3%) of developing ovarian cancer by age 50 years and a risk of 4.8% (95% CI, 2.4% – 9.7%) of developing ovarian cancer by age 80 years.

PALB2 pathogenic variants were associated with an estimated 2-fold higher RR for pancreatic cancer (RR, 2.37; 95% CI, 1.24-4.50; P =8.7 × 10-3), which translated into an absolute risk among women of 2.2% (95% CI, 1.2%-4.2%) and a risk of 2.8% (95% CI, 1.5%-5.3%) among men of developing pancreatic cancer by age 80 years.

PALB2 pathogenic variants were associated with an estimated 7-fold higher RR for male breast cancer (RR, 7.34; 95% CI, 1.28-42.18; P =2.6 × 10-2), which translated into an absolute risk of 0.9% (95% CI, 0.2% – 4.9%) of developing male breast cancer by age 80 years.

PALB2 pathogenic variants were not associated with an increased risk for prostate or colorectal cancers.

“These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs [pathogenic variants] and ovarian, pancreatic, and male breast cancers,” the study authors concluded.

Disclosure: Some of the authors of this article financial relationships with pharmaceutical and medical device companies. For a full list of disclosures, please refer to the original study.

Reference

Yang X, Leslie G, Doroszuk A, et al. Cancer risks associated with germline PALB2 pathogenic variants: An international study of 524 families. J Clin Oncol. doi: 10.1200/JCO.19.01907

This article was published by Cancer Therapy Advisor.

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