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

被引：3

作者：

Sargen, Michael R. ^{[1
,6
]}

Helgadottir, Hildur ^{[2
]}

Yang, Xiaohong R. ^{[1
]}

Harland, Mark ^{[3
]}

Hatton, Jessica N. ^{[1
]}

Jones, Kristine ^{[1
]}

Hicks, Belynda D. ^{[1
,4
]}

Hutchinson, Amy ^{[1
,4
]}

Curry, Michael ^{[5
]}

Tucker, Margaret A. ^{[1
]}

Goldstein, Alisa M. ^{[1
]}

Pfeiffer, Ruth M. ^{[1
]}

机构：

[1] NIH, NCI, Div Canc Epidemiol & Genet, Rockville, MD USA

[2] Karolinska Univ Hosp, Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden

[3] Univ Leeds, Leeds Inst Canc & Pathol, Sect Epidemiol & Biostat, Leeds, England

[4] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Canc Genom Res Lab, Bethesda, MD USA

[5] Informat Management Serv Inc, Calverton, MD USA

[6] NIH, NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Room 6E-542, Rockville, MD 20850 USA

来源：

JNCI CANCER SPECTRUM | 2022年 / 6卷 / 06期

基金：

美国国家卫生研究院;

关键词：

NEURAL SYSTEM TUMORS; PANCREATIC-CANCER; FAMILIAL MELANOMA; DYSPLASTIC NEVI; NERVOUS-SYSTEM; LUNG-CANCER; MUTATIONS; DELETION; BREAST; SURVEILLANCE;

D O I：

10.1093/jncics/pkac074

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：9

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