JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients

被引：21

作者：

Guerrero-Preston, Rafael ^{[1
,2
]}

Lawson, Fahcina ^{[1
]}

Rodriguez-Torres, Sebastian ^{[1
,3
]}

Noordhuis, Maartje G. ^{[1
,4
]}

Pirini, Francesca ^{[5
]}

Manuel, Laura ^{[6
]}

Valle, Blanca L. ^{[1
]}

Hadar, Tal ^{[7
]}

Rivera, Bianca ^{[8
]}

Folawiyo, Oluwasina ^{[1
]}

Baez, Adriana ^{[8
]}

Marchionni, Luigi ^{[9
]}

Koch, Wayne M. ^{[1
]}

Westra, William H. ^{[10
]}

Kim, Young J. ^{[11
]}

Eshleman, James R. ^{[12
]}

Sidransky, David ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Otolaryngol & Head & Neck Surg, Baltimore, MD USA

[2] Univ Puerto Rico, Sch Med, Dept Obstet & Gynecol, San Juan, PR 00936 USA

[3] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[4] Univ Groningen, Univ Med Ctr Groningen, Dept Otorhinolaryngol Head & Neck Surg, Groningen, Netherlands

[5] IRCCS, Biosci Lab, Ist Sci Romagnolo Studio & Cura Tumori IRST, Meldola, Italy

[6] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA

[7] Shaare Zedek Med Ctr, Dept Gen Surg, Breast Hlth Unit, Jerusalem, Israel

[8] Univ Puerto Rico, Sch Med, Dept Otolaryngol, San Juan, PR 00936 USA

[9] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[10] Mt Sinai Hosp, Dept Pathol, Icahn Sch Med, New York, NY 10029 USA

[11] Vanderbilt Univ, Sch Med, Dept Otolaryngol, Nashville, TN 37212 USA

[12] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

来源：

CANCER PREVENTION RESEARCH | 2019年 / 12卷 / 04期

关键词：

SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS HPV; RACIAL/ETHNIC DISPARITIES; AFRICAN-AMERICAN; EPIGENETIC INACTIVATION; SOMATIC MUTATIONS; GENE-EXPRESSION; BREAST-CANCER; POSITIVE HEAD; LUNG-CANCER;

D O I：

10.1158/1940-6207.CAPR-17-0356

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

To inform novel personalized medicine approaches for race and socioeconomic disparities in head and neck cancer, we examined germline and somatic mutations, immune signatures, and epigenetic alterations linked to neighborhood determinants of health in Black and non-Latino White (NLW) patients with head and neck cancer. Cox proportional hazards revealed that Black patients with squamous cell carcinoma of head and neck (HNSCC) with PAX5 (P = 0.06) and PAX1 (P = 0.017) promoter methylation had worse survival than NLW patients, after controlling for education, zipcode, and tumor-node-metastasis stage (n = 118). We also found that promoter methylation of PAX1 and PAX5 (n = 78), was correlated with neighborhood characteristics at the zip-code level (P < 0.05). Analyses also showed differences in the frequency of TP53 mutations (n = 32) and tumor-infiltrating lymphocyte (TIL) counts (n = 24), and the presence of a specific C -> A germline mutation in JAK3, chr19:17954215 (protein P132T), in Black patients with HNSCC (n = 73; P < 0.05), when compared with NLW (n = 37) patients. TIL counts are associated (P = 0.035) with long-term (>5 years), when compared with short-term survival (<2 years). We show bio-social determinants of health associated with survival in Black patients with HNSCC, which together with racial differences shown in germline mutations, somatic mutations, and TIL counts, suggests that contextual factors may significantly inform precision oncology services for diverse populations.

引用

页码：255 / 270

页数：16