Dataset Information

Genetic susceptibility to patient-reported xerostomia among long-term oropharyngeal cancer survivors.

ABSTRACT: Genetic susceptibility for xerostomia, a common sequela of radiotherapy and chemoradiotherapy for head and neck cancer, is unknown. Therefore, to identify genetic variants associated with moderate to severe xerostomia, we conducted a GWAS of 359 long-term oropharyngeal cancer (OPC) survivors using 579,956 autosomal SNPs. Patient-reported cancer treatment-related xerostomia was assessed using the MD Anderson Symptom Inventory. Patient response was dichotomized as moderate to severe or none to mild symptoms. In our study, 39.2% of OPC survivors reported moderate to severe xerostomia. Our GWAS identified eight SNPs suggestively associated with higher risk of moderate to severe xerostomia in six genomic regions (2p13.3, rs6546481, Minor Allele (MA) = A, ANTXR1, P = 4.3 × 10^-7; 5p13.2-p13.1, rs16903936, MA = G, EGFLAM, P = 5.1 × 10^-6; 4q21.1, rs10518156, MA = G, SHROOM3, P = 7.1 × 10^-6; 19q13.42, rs11882068, MA = G, NLRP9, P = 1.7 × 10^-5; 12q24.33, rs4760542, MA = G, GLT1D1, P = 1.8 × 10^-5; and 3q27.3, rs11714564, MA = G, RTP1, P = 2.9 × 10^-5. Seven SNPs were associated with lower risk of moderate to severe xerostomia, of which only one mapped to specific genomic region (15q21.3, rs4776140, MA = G, LOC105370826, a ncRNA class RNA gene, P = 1.5 × 10^-5). Although our small exploratory study did not reach genome-wide statistical significance, our study provides, for the first time, preliminary evidence of genetic susceptibility to xerostomia. Further studies are needed to elucidate the role of genetic susceptibility to xerostomia.

SUBMITTER: Aggarwal P

PROVIDER: S-EPMC9033773 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Genetic susceptibility to patient-reported xerostomia among long-term oropharyngeal cancer survivors.

Aggarwal Puja P Hutcheson Katherine A KA Yu Robert R Wang Jian J Fuller Clifton D CD Garden Adam S AS Goepfert Ryan P RP Rigert Jillian J Mott Frank E FE Lu Charles C Lai Stephen Y SY Gunn G Brandon GB Chambers Mark S MS Li Guojun G Wu Chih-Chieh CC Hanna Ehab Y EY Sturgis Erich M EM Shete Sanjay S

Scientific reports 20220422 1

Genetic susceptibility for xerostomia, a common sequela of radiotherapy and chemoradiotherapy for head and neck cancer, is unknown. Therefore, to identify genetic variants associated with moderate to severe xerostomia, we conducted a GWAS of 359 long-term oropharyngeal cancer (OPC) survivors using 579,956 autosomal SNPs. Patient-reported cancer treatment-related xerostomia was assessed using the MD Anderson Symptom Inventory. Patient response was dichotomized as moderate to severe or none to mil ...[more]

PMID: 35459784

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Project description:ImportanceVoice and speech production are critical physiological functions that affect quality of life and may deteriorate substantially after oropharyngeal cancer (OPC) treatment. There is limited knowledge about risk factors associated with voice and speech outcomes among survivors of OPC.ObjectiveTo identify the risk factors of voice and speech symptoms among long-term survivors of OPC.Design, setting, and participantsThis retrospective cohort study with cross-sectional survivorship survey administration includes cancer-free survivors of OPC who were treated curatively between January 2000 and December 2013 at MD Anderson Cancer Center (Houston, Texas) who participated in a survey from September 2015 to July 2016. Of 906 survivors of OPC with a median survival duration at time of survey of 6 years (range, 1-16 years), patient-rated voice and speech outcomes for 881 were available and analyzed. The data were analyzed from June 30, 2020, to February 28, 2021.Main outcomes and measuresThe primary outcome variable was patient-reported voice and speech scores that were measured using the MD Anderson Symptom Inventory-Head and Neck Cancer Module. Voice and speech scores of 0 to 4 were categorized as none to mild symptoms, and scores of 5 to 10 were categorized as moderate to severe symptoms. Risk factors for moderate to severe voice and speech symptoms were identified by multivariable logistic regression.ResultsAmong 881 survivors of OPC (median [range] age, 56 [32-84] years; 140 women [15.5%]; 837 White [92.4%], 17 Black [1.9%], and 35 Hispanic individuals [3.8%]), 113 (12.8%) reported moderate to severe voice and speech scores. Increasing survival time (odds ratio [OR], 1.17; 95% CI, 1.06-1.30) and increasing total radiation dose (OR, 1.16; 95% CI, 1.00-1.34), Black race (OR, 3.90; 95% CI, 1.02-14.89), Hispanic ethnicity (OR, 3.74; 95% CI, 1.50-9.35), current cigarette smoking at the time of survey (OR, 3.98; 95% CI, 1.56-10.18), treatment with induction and concurrent chemotherapy (OR, 1.94; 95% CI, 1.06-3.57), and late (OR, 7.11; 95% CI, 3.08-16.41) and baseline lower cranial neuropathy (OR, 8.70; 95% CI, 3.01-25.13) were risk factors associated with moderate to severe voice and speech symptoms. Intensity-modulated radiotherapy split-field regimen (OR, 0.31; 95% CI, 0.12-0.80; P = .01) was associated with lower likelihood of moderate to severe voice and speech symptoms.Conclusions and relevanceThis large OPC survivorship cohort study identified many treatment-related factors, including increasing total radiotherapy dose, multimodality induction and concurrent chemotherapy regimens, and continued smoking, as well as clinical and demographic factors, as risk factors that were associated with moderate to severe voice and speech symptoms. The key findings in this study were the protective associations of split-field radiation and that longer-term survivors, and those who continued to smoke, had worse voice and speech symptoms. These findings may inform research and effective targeted clinical voice and speech preservation interventions and smoking cessation interventions to maximize voice and speech function and address quality of life among patients with OPC.

Project description:BackgroundDue to advances in screening and treatment of lung cancer, there has been increased interest in long-term lung cancer survivors (LTLCS). The aim of this study was to evaluate the prevalence of LTLCS, their characteristics and patient-reported outcomes (PROs) of LTLCS.MethodsCross-sectional study that included patients diagnosed with primary lung cancer between Jan 2012 and Dec 2016 whose overall survival (OS) was greater than 5 years. A self-administered questionnaire was applied, including European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30), Patient Health Questionnaire-4 (PHQ-4) and two open questions regarding quality of life (QoL) and suggestions for improvements. Factors potentially related to QoL were analysed.ResultsOf 767 lung cancer patients, 158 (20.6%) were LTLCS and LTLCS' proportion increased yearly. Most patients were male (70.9%) with median age of 65 [interquartile range (IQR), 56-71] years. Fifty-seven percent had adenocarcinoma, 66.2% were diagnosed at early stages but 8.9% were at stage IV. During follow-up, 77.1% quitted smoking, 31.8% had disease progression/relapse and 15.2% developed other tumours. Of all living LTLCS, 100 (85%) patients answered the PROs questionnaire. The median Global Health score was 66.67 (IQR, 50-83), social functioning had the best score and emotional functioning the worst. Pain and fatigue were the symptoms with the worst impact on QoL. PHQ-4 identified mental distress in 36% and patients with a lower QoL were more likely to present anxiety (35.3% vs. 9.4%, P=0.007) or depression (27.9% vs. 3%, P=0.006). In the open questions, patients reported pain (17%), lack of familiar/financial support (16%), dyspnoea (14%), depression (8%), concern for the future (8%) and limitations performing daily activities (8%) as the aspects with most impact in QoL. The most suggested measures were improvement of care provided by health institutions (25%) and better social support (16%).ConclusionsPrevalence of LTLCS is increasing and survivors may experience a high prevalence of anxiety and depression as well as a high disease burden affecting QoL. Therefore, it's important to provide multidisciplinary continuous patient-centred care and a careful follow-up for all lung cancer patients, including LTLCS.

Project description:PurposeFor older women with breast cancer, local therapy options may include lumpectomy plus whole-breast irradiation (Lump + WBI), lumpectomy plus brachytherapy (Lump + Brachy), lumpectomy alone (Lump alone), mastectomy without radiation therapy (Mast alone), and mastectomy plus radiation therapy (Mast + RT). We surveyed a population-based cohort of older breast cancer survivors to assess the association of local therapy with long-term quality-of-life outcomes.Methods and materialsWe used nationally comprehensive Medicare claims to identify women aged ≥67 years in whom nonmetastatic breast cancer was diagnosed in 2009, who were treated with 1 of the 5 aforementioned treatment options, and who were still alive in 2015. From this cohort, 1650 patients (330 patients per treatment) were randomly selected. A survey that included the CanSORT (Cancer Surveillance and Outcomes Research Team) Satisfaction with Breast Cosmetic Outcome, BREAST-Q, Decisional Regret Scale, and EQ-5D-3L was mailed to potential participants. We used multivariable linear regression to assess associations between local therapy and outcomes after adjusting for patient, disease, and treatment covariates.ResultsAmong the 489 women who returned the surveys (30% response rate), the median age at diagnosis was 72 years (range, 67-87 years). The interval from diagnosis to survey completion was approximately 6 years for all patients. Compared with Lump + WBI (adjusted score, 3.40), the CanSORT cosmetic satisfaction scores were higher for Lump + Brachy (score, 3.77; P = .007) and Lump alone (score, 3.80; P = .04) and lower for Mast + RT (score, 3.01; P = .006). Similar trends were seen for BREAST-Q cosmetic satisfaction. BREAST-Q psychosocial, sexual, and physical well-being and EQ-5D-3L global health status tended to be better in patients treated with less irradiation and less surgery. BREAST-Q adverse radiation effects were worse for Lump + WBI compared with Lump + Brachy. Decisional regret regarding surgery and radiation therapy did not differ across groups. Compared with patients treated with Lump + WBI, patients treated with Lump + Brachy and Lump alone reported slightly higher rates of in-breast recurrence (excess risk of 5.8% and 6.4%, respectively; P = .01).ConclusionsIn this nationally diverse cohort, less irradiation and less surgery were associated with better long-term quality-of-life outcomes. However, patient regret regarding surgery and radiation therapy was similar across all groups.

Dataset Information

Genetic susceptibility to patient-reported xerostomia among long-term oropharyngeal cancer survivors.

Publications

Genetic susceptibility to patient-reported xerostomia among long-term oropharyngeal cancer survivors.

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