A two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer.

BACKGROUND: Most head and neck cancer (HNC) patients receive radiotherapy (RT) and develop toxicities. This genome-wide association study (GWAS) was designed to identify single nucleotide polymorphisms (SNPs) associated with common acute radiation-induced toxicities (RITs) in an HNC cohort. METHODS: A two-stage GWAS was performed in 1279 HNC patients treated with RT and prospectively scored for mucositis, xerostomia, sticky saliva, and dysphagia. The area under the curve (AUC) was used to estimate the average load of toxicity during RT. At the discovery study, multivariate linear regression was used in 957 patients, and the top-ranking SNPs were tested in 322 independent replication cohort. Next, the discovery and the replication studies were meta-analyzed. RESULTS: A region on 5q21.3 containing 16 SNPs showed genome-wide (GW) significance association at P-value < 5.0 × 10-8 with patient-rated acute xerostomia in the discovery study. The top signal was rs35542 with an adjusted effect size of 0.17*A (95% CI 0.12 to 0.23; P-value < = 3.78 × 10-9). The genome wide significant SNPs were located within three genes (EFNA5, FBXL17, and FER). In-silico functional analysis showed these genes may be involved in DNA damage response and co-expressed in minor salivary glands. We found 428 suggestive SNPs (P-value < 1.0 × 10-5) for other toxicities, taken to the replication study. Eleven of them showed a nominal association (P-value < 0.05). CONCLUSIONS: This GWAS suggested novel SNPs for patient-rated acute xerostomia in HNC patients. If validated, these SNPs and their related functional pathways could lead to a predictive assay to identify sensitive patients to radiation, which may eventually allow a more individualized RT treatment.

Postpartum Weight Change in Relation to Pre-Pregnancy Weight and Gestational Weight Gain in Women in Low-Income Setting: Data from the KITE Cohort in the Northern Part of Ethiopia.

(1) Background: Postpartum weight may increase compared to pre-pregnancy due to weight retention or decrease due to weight loss. Both changes could pose deleterious effects on maternal health and subsequent pregnancy outcomes. Therefore, this study aimed to assess postpartum weight change and its associated factors. (2) Methods: A total of 585 women from the KIlte-Awlaelo Tigray Ethiopia (KITE) cohort were included in the analysis. (3) Results: The mean pre-pregnancy body mass index and weight gain during pregnancy were 19.7 kg/m2 and 10.8 kg, respectively. At 18 to 24 months postpartum, the weight change ranged from -3.2 to 5.5 kg (mean = 0.42 kg [SD = 1.5]). In addition, 17.8% of women shifted to normal weight and 5.1% to underweight compared to the pre-pregnancy period. A unit increase in weight during pregnancy was associated with higher weight change (ß = 0.56 kg, 95% CI [0.52, 0.60]) and increased probability to achieve normal weight (AOR = 1.65, 95% CI [1.37, 2.00]). Food insecurity (AOR = 5.26, 95% CI [1.68, 16.50]), however, was associated with a shift to underweight postpartum. Interestingly, high symptoms of distress (AOR = 0.13, 95% CI [0.03, 0.48]) also negatively impacted a change in weight category. (4) Conclusions: In low-income settings such as northern Ethiopia, higher weight gain and better mental health during pregnancy may help women achieve a better nutritional status after pregnancy and before a possible subsequent pregnancy.

Adiposity and High Blood Pressure during Childhood: A Prospective Analysis of the Role of Physical Activity Intensity and Sedentary Time in the GECKO Drenthe Cohort.

Whereas in adults, physical inactivity is strongly related to obesity and hypertension, in young children the evidence is inconsistent and scarce. We examined the association between physical activity (PA) behaviours at 5-6 years of age and adiposity and blood pressure (BP) at 10-11 years in 947 children (51% boys) from the Groningen Expert Center for Kids with Obesity (GECKO) Drenthe cohort. Sedentary time (ST) and light, moderate, and vigorous PA were assessed using accelerometry (ActiGraph GT3X, wear time > 600 min/day, ≥3 days). Body mass index (BMI), waist circumference (WC), and systolic and diastolic BP were measured at 5-6 and 10-11 years of age and standardized as age- and sex-adjusted (and height-adjusted, for BP) z-scores. Adjusted linear and logistic regression models showed that most PA behaviours were not related to standardized BMI or WC, overweightness/obesity, abdominal overweightness/obesity, standardized systolic or diastolic BP, pulse pressure, or prehypertension at 10-11 years of age. Only if children spent more time in vigorous PA was WC slightly lower (B (95% CI) = -0.08 (-0.16, -0.01) SD, stdß = -0.068) and the increase in WC over the years was less (B (95% CI) = -0.10 (-0.18, -0.01) SD; stdß = -0.083). To conclude, at this very young age, PA behaviours are not a strong predictor for overweightness/obesity or hypertension later in childhood.