Impact of Transcript (p16/p14ARF) Alteration on Cancer Risk in CDKN2A Germline Pathogenic Variant Carriers
Menée à partir de données portant sur 385 porteurs de variants pathogènes constitutionnels du gène CDKN2A, cette étude analyse l'association entre des altérations au niveau des transcrits p16 et p14ARF et le risque de cancer
Few studies have evaluated the relationship between CDKN2A germline pathogenic variants (GPV), transcript (p16, p14ARF) alteration, and cancer risk.Standardized incidence ratios (SIRs) comparing cancer risk to the general population were calculated for 385 CDKN2A GPV carriers from two large cohorts (259 United States and 126 Swedish individuals) using Poisson regression; statistical significance was defined as P<.002 (Bonferroni correction). Cumulative incidence is reported for melanoma and non-melanoma cancer.Incidence was significantly 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 (HNSCC; 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 for melanoma and non-melanoma cancer was 68.3% (95% CI = 68.0 to 68.6) and 35.2% (95% CI = 34.9 to 35.6), respectively. 89% of smoking-related cancers (lung, HNSCC, pancreatic, esophageal) occurred in ever smokers.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.
JNCI Cancer Spectrum 2022