Impact of Transcript (p16/p14ARF) Alteration on Cancer Risk in CDKN2A Germline Pathogenic Variant Carriers.

Abstract

BACKGROUND:

Few studies have evaluated the relationship between CDKN2A germline pathogenic variants (GPV), transcript (p16/p14ARF) alteration, and cancer risk.

METHODS:

Standardized incidence ratios (SIRs) comparing cancer risk with the general population were calculated for 385 CDKN2A GPV carriers from 2 large cohorts (259 United States and 126 Swedish individuals) using Poisson regression; statistical significance was defined as P less than .002 (Bonferroni correction). Cumulative incidence is reported for melanoma and nonmelanoma cancer.

RESULTS:

Incidence was increased for melanoma (SIR = 159.8, 95% confidence interval [CI] = 132.1 to 193.2), pancreatic cancer (SIR = 24.1, 95% CI = 14.7 to 39.4), head and neck squamous cell carcinoma (SIR = 16.2, 95% CI = 9.5 to 27.6), and lung cancer (SIR = 5.6, 95% CI = 3.4 to 9.1) in GPV carriers. Similar associations were observed with p16 alteration. Combined p16 and p14ARF alteration was associated with increased incidence of esophageal cancer (SIR = 16.7, 95% CI = 5.7 to 48.9) and malignant peripheral nerve sheath tumor (SIR = 113.0, 95% CI = 16.4 to 780.9), although cancer events were limited (n < 5 for each malignancy). Cumulative incidence at age 70 years for melanoma and nonmelanoma cancer was 68.3% (95% CI = 68.0% to 68.6%) and 35.2% (95% CI = 34.9% to 35.6%), respectively. A total 89% of smoking-related cancers (lung, head and neck squamous cell carcinoma, pancreatic, esophageal) occurred in ever smokers.

CONCLUSION:

These findings highlight the impact of p16 and p14ARF alteration on cancer risk. Smoking was an important risk factor for smoking-related cancers in our study.

• Authors: Michael R Sargen, Hildur Helgadottir, Xiaohong R Yang, Mark Harland, Jessica N Hatton, Kristine Jones, Belynda D Hicks, Amy Hutchinson, Michael Curry, Margaret A Tucker, Alisa M Goldstein, Ruth M Pfeiffer
• Journal: JNCI cancer spectrum (JNCI Cancer Spectr) Vol. 6 Issue 6 (11 01 2022) ISSN: 2515-5091 [Electronic] England
• PMID: 36269225 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: Published by Oxford University Press 2022.

Chemical References

• Tumor Suppressor Protein p14ARF
• Cyclin-Dependent Kinase Inhibitor p16
• CDKN2A protein, human

Topics

• Humans
• United States
• Aged
• Tumor Suppressor Protein p14ARF (genetics)
• Squamous Cell Carcinoma of Head and Neck (epidemiology)
• Cyclin-Dependent Kinase Inhibitor p16 (genetics)
• Melanoma (epidemiology)
• Risk Factors
• Head and Neck Neoplasms