[en] It is well known from clinical experience that acute complications of chemoradiation therapy vary from patients to patients. However, there are no known factors to predict these acute complications before treatment starts. The human XRCC1 gene is known as a DNA base excision repair gene. We investigated the possibilities of XRCC1 gene polymorphisms as a predictor for the acute complications of chemoradiation therapy in colorectal cancer patients. From July 1997 to June 2003, 86 colorectal cancer patients (71 rectal cancer, 13 sigmoid colon cancer and 2 colon cancer patients) were treated with chemoradiation therapy at the Department of Radiation Oncology, Inha University Hospital. Twenty-two patients were in stage B, 50 were in stage C, 8 were in stage D and 6 patients were unresectable cases. External radiation therapy was delivered with 10MV X-ray at a 1.8 Gy fraction per day for a total dose of radiation of 30.6 ∼ 59.4 Gy (median: 54 Gy). All the patients received 5-FU based chemotherapy regimen. We analyzed the acute complications of upper and lower gastrointestinal tract based on the RTOG complication scale. The initial and lowest WBC and platelet count were recorded during both the RT period and the whole treatment period. Allelic variants of the XRCC1 gene at codons 194, 280 and 399 were analyzed in the lymphocyte DNA by performing PCR-RFLP. Statistical analyses were carried out with the SAS (version 6.12) statistical package. When all the variables were assessed on the multivariate analysis, recurrent disease revealed the factors that significantly correlated with upper gastrointestinal acute complications. Arg399Gln polymorphisms of the XRCC1 gene, the radiation dose and the frequencies of chemotherapy during radiation therapy were significantly correlated with lower gastrointestinal complications. Arg399Gln polymorphisms also affected the decrease of the WBC and platelet count during radiation therapy. Although the present sample size was too small for fully evaluating this hypothesis, this study suggests that Arg399Gln polymorphisms of the XRCC1 genes may be used as one of the predictors for acute complications of chemoradiation therapy in colorectal cancer patients

[en] NAD(P)H:quinone oxidoreductase 1 (NQO1) has been known to function on reduction of oxidative status as a cytosolic flavoenzyme that catalyzes the electron reduction of substrates. It was reported to play a role in the prognosis of lung cancer patients treated with chemotherapy. Single nucleotide polymorphisms (SNPs) make up about ninety percent of human DNA polymorphisms, and they are a major focus of study about the individual differences for the risk of cancer and for anti-cancer treatment. A point mutation in exon 6 of the NQO1 gene is a C-to-T base pair substitution at position 609 of the NQO1 cDNA, and this codes for a proline-to-serine change at position 187 in the amino acid sequence of the protein. We hypothesized that NQO1 polymorphism could have an adverse influence on the survival of NSCLC patients treated with radiation therapy and/or surgery, and so we tried to discover whether the NQO1 polymorphism could be a predictive or prognostic marker for determining treatment outcome of radiotherapy in nonsmall cell lung cancer (NSCLC) patients

[en] Despite their popular use and emerging evidences of adverse health effects, consequent trends in population level triclosan and benzophenone-3 exposure have been poorly evaluated. Therefore, we examined temporal trends of urinary triclosan and benzophenone-3 concentration in the general U.S. population by combining five cycles of National Health and Nutritional Examination Survey (NHANES, 2003–2012) data. We calculated percent changes and the least square geometric means (LSGMs) of urinary triclosan and benzophenone-3 concentration from 10,232 participants by using multivariable regression models. As a result, LSGM concentration of urinary triclosan and benzophenone-3 did not show statistically significant changes over the study period. [Percent change (95% CI): Triclosan, −7.35% (−20.86, 8.47); Benzophenone-3, 7.08% (−27.88, 58.99)] However, we found decreasing trend of urinary triclosan concentration and increasing trend of urinary benzophenone-3 concentration since 2005–2006. Socio-demographic factors which affected urinary concentration of triclosan and benzophenone-3 persisted throughout 10 year study period. Highest income group showed higher level of urinary triclosan and benzophenone-3 concentration. Overall concentration of benzophenone-3 was higher in female than in male, and higher in non-Hispanic Whites than any other races/ethnicities. - Highlights: • We analyzed 2003–2012 NHANES to evaluate temporal trends in triclosan and BP3 exposure levels. • There was decreasing trend of urinary triclosan concentration since 2005–2006. • There was increasing trend of urinary BP3 concentration since 2005–2006. • Urinary triclosan and BP3 concentration of each NHANES cycle varied by socio-demographic factors. - In the analysis of 2003–2012 National Health and Nutrition Examination Surveys data, we found decreasing trend of urinary triclosan concentration and increasing trend of urinary Benzophenone-3 concentration since 2005–2006.

[en] Highlights: • We did a systematic review of studies on blood pressure effects of PM respirator use. • Seven randomized crossover studies were selected for our systematic review. • Use of PM respirator was associated with −1.23 and −1.57 mmHg change in SBP and MAP. • However, significant heterogeneities and publication bias were observed. • Further interventions on blood pressure effects of PM respirator are needed. People use a particulate respirator in order to reduce exposure to ambient fine particulate matter (PM_2.5). Acute exposure to PM_2.5 is known to increase blood pressure. However, systematic reviews or meta-analyses on blood pressure-related benefits of using a particulate respirator is lacking. Therefore, we reviewed randomized crossover intervention studies on blood pressure-related effects of particulate matter respirator use. We conducted a literature review of articles found on Embase, Medline, and Cochrane library on August 31, 2020. The study outcomes were systolic and diastolic blood pressure and mean arterial pressure. A random-effect model was used in the meta-analysis. Subgroup analyses, based on age (adult < 60 years, elderly ≥ 60 years), personal PM_2.5 exposure levels (High: ≥ 25 μg/m³, Low: < 25 μg/m³), and types of monitoring methods (ambulatory and resting blood pressure) were conducted. We identified 297 references, and seven studies were included in our systematic review. None of the studies used a sham respirator as control and complete allocation concealment and blinding were impossible. The use of a particulate respirator was associated with a −1.23 mmHg (95% confidence interval (CI): −2.53, 0.07) change in systolic blood pressure and a −1.57 mmHg (95% CI: −3.85, 0.71) change in mean arterial pressure. There were significant heterogeneities and possibilities for publication bias. The subgroup analyses revealed that studies involving elderly individuals, those conducted in high PM_2.5 personal exposure, and those in which resting blood pressure was monitored demonstrated a larger decrease in blood pressure resulting from respirator use. Further intervention studies with a large sample size and subjects with diverse characteristics and different personal PM_2.5 levels may add the evidence to current literature.

[en] Highlights: • We examined the relationship of maternal air pollution exposure with fetal growth. • NO₂ was associated with decreased biparietal diameter (BPD) in second trimester. • PM₁₀ was inversely associated with BPD in third trimester. • Air pollution in third trimester was inversely associated with birth head circumference. Few studies have examined the effects of air pollution on fetal growth based on ultrasound measures during pregnancy. More data is needed to evaluate the windows of special vulnerability. Our aim was to investigate the association of ambient air pollution during pregnancy with fetal and neonatal characteristics in a cohort of Korean women. Maternal exposure to particulate matter with an aerodynamic diameter < 10 μm (PM₁₀) and nitrogen dioxide (NO₂) was estimated using land-use regression models based on residential address. The biparietal diameter (BPD), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW) were evaluated via ultrasonography, and birth weight (BW), birth length (BL), and head circumference at birth (BHC) were obtained from medical records. The multiple linear regression model was used to adjust for confounders, and the mixed-effect model was used to evaluate longitudinal effect. The negative effects for NO₂ and PM₁₀ were estimated; in the adjusted analyses the decreases of BPD were − 0.26 mm (95% confidence interval [CI] = − 0.41 to − 0.11, with a 10 μg/m³ increase) in the second trimester for NO₂, and − 0.30 mm (95% CI = − 0.59 to − 0.03, with a 10 μg/m³ increase) in the third trimester for PM₁₀. Both NO₂ and PM₁₀ levels (10 μg/m³) during third trimester were inversely associated with BHC, and NO₂ level was inversely associated with BL in all exposure windows. No significant associations for AC, FL, and EFW were observed. The longitudinal analyses showed inverse association of NO₂ exposure with head and length growth (P < 0.001). Our findings suggest that ambient air pollution is associated with impaired fetal head size from mid-gestation onwards.

[en] Highlights: • The effects of di-(2-ethylhexyl) phthalate (DEHP) on the neurodevelopmental outcomes in children need to be synthesized. • This meta-analysis showed that exposure to DEHP in childhood has an adverse association with the intelligence quotient. • Exposure to DEHP in prenatal period was negatively associated with psychomotor development of childhood. • Further studies considering an exposure assessment of DEHP and measurement timings of neurodevelopment outcomes are required. Di-(2-ethylhexyl) phthalate (DEHP), the most widely used phthalate, has recently been associated with neurodevelopmental disturbances in children. However, the risk is yet to be quantified. Therefore, a systematic review and meta-analysis focusing on the association between exposure to DEHP and neurodevelopmental outcomes is necessary, with particular attention to study design (longitudinal vs. cross-sectional).

[en] Highlights: • Urinary 3-PBA is a biomarker of pyrethroids related with adverse health outcomes. • We repeatedly measured urinary 3-PBA levels and pulmonary function in urban elderly. • Community-level exposure to pyrethroids induced pulmonary function reduction. • Stringent control of pyrethroids is necessary to protect health of the elderly. -- Abstract: Pyrethroids are a class of man-made insecticides associated with various adverse health outcomes including respiratory problems. However, there were limited evidences on the relation between 3-phenoxybenzoic acid (3-PBA) as a metabolite of pyrethroids and pulmonary function, particularly among elderly population who have declining pulmonary function. Therefore, we collected urine samples and performed pulmonary function test (PFT) repeatedly in a total of 559 Korean elderly living in Seoul as an urban area. After measurement of urinary 3-PBA levels, cross-sectional relations of visit-to-visit variation in 3-PBA level on visit-to-visit variation in PFT parameters were evaluated using linear mixed effect models and generalized additive mixed models after adjustment for age, sex, body mass index, smoking status, education, visit episode, and phthalate metabolite levels. The Korean elderly were highly exposed to pyrethroids with 30.2% of elderly people with 3-PBA level over reference value derived on the 95th percentile of representative samples (2 ng/mL). Forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of FVC (FEF_25–75) as PFT parameters showed significant reductions by an increase of 3-PBA level (FEV₁, β = −1.48, p-value < 0.01; FVC, β = −1.14, p-value < 0.01; and FEF_25-75, β = −1.11, p-value = 0.03). The negative associations of 3-PBA level with FEV₁, FVC, and FEF_25-75 were found only for females (FEV₁, β = −1.64, p-value < 0.01; FVC, β = −1.47, p-value < 0.01; and FEF_25-75, β = −1.06, p-value = 0.07), but not for males. However, the longitudinal effect of 3-PBA level on the trajectory of FEV₁, FVC, and FEF_25-75 declines in females was not found. Community-level exposure to pyrethroids was associated with pulmonary function reduction in elderly population, indicating that more stringent control of pyrethroids is necessary to protect the elderly who have declining pulmonary function.

[en] Highlights: • High temperature and acute kidney injury have a strong relationship. • A nonlinear relationship with a flexion point was observed in the warm season. • Men with hypertension were most vulnerable to high ambient temperatures. Some studies have suggested that high ambient temperatures are a risk factor for kidney-related diseases. However, none have examined the association between ambient temperature and acute kidney injury (AKI). This study aimed to examine the association between daily mean temperature and AKI and identify high-risk subgroups in this association. We obtained health insurance claim data from the Health Insurance Review and Assessment Service (HIRA) for 24,800 admitted cases of AKI during the period 2007–2014 in Seoul, Korea. Using a time-series design and piecewise linear regression models, we estimated the percentage change in AKI admissions associated with daily mean temperature after controlling for relevant covariates. Daily mean temperature and AKI admissions displayed an inverse association in the cold season and a nonlinear relationship with a flexion point around 28.8 °C in the warm season. AKI admissions increased by 23.3% (95% confidence interval [CI]: 14.3, 33.0) per 1 °C increase in mean temperature above the 28.8 °C flexion point in the warm season. The estimates were greatest among men with hypertension (55.1%; 95% CI: 25.1, 92.2). However, we did not observe significant increases in AKI admissions associated with ambient temperature in the cold season (0.4% [95% CI: − 0.1, 0.9] per 1 °C decrease in mean temperature). Our results suggest that hospital admissions for AKI increase in association with high temperature, particularly among men with hypertension in the warm season. Thus, early detection of AKI during heat wave periods is crucial. Our findings also provide evidence for the local government to target populations vulnerable to high ambient temperatures.

[en] Highlights: • Phthalate exposure affects the development of a variety of diseases in the elderly. • We repeatedly determined urinary DEHP and DnBP metabolite levels in Korean elderly. • DEHP and DnBP variations were mainly attributed to intra-individual variation. • DEHP exposure was strongly correlated to DnBP exposure. • Urine samples with DEHP > RfD and DnBP > TDI were 20.2% and 3.6%, respectively. Recent studies indicated that exposure to phthalates affects the development of a variety of diseases in the elderly population. However, limited information was available about the variability of phthalate daily intakes (DIs) and the proportion of the population that is highly exposed to phthalates. Therefore, we measured the levels of three phthalate metabolites, mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MnBP) in 4014 urine samples repeatedly collected from 1646 elderly people. The DIs of di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DnBP) were calculated using urinary MEHHP, MEOHP, and MnBP levels, and then the proportion of the population that was highly exposed to DEHP and DnBP was calculated. The intra-class correlation (ICC) for MEHHP, MEOHP, and MnBP levels was 0.07, 0.02, and 0.03, respectively, and exposures to DEHP and DnBP were strongly correlated with each other (correlation coefficient = 0.89 and p-value < 0.0001). The geometric mean of estimated DI was 8.8 μg/kg_body-weight/day (range 0.005–3382.0) for DEHP and 1.5 μg/kg_body-weight/day (range 0.0002–1076.8) for DnBP. The percentages of urine samples with DEHP > reference dose (RfD, 20 μg/kg_body-weight/day) and DnBP > tolerable daily intake (TDI, 10 μg/kg_body-weight/day) were 20.2% and 3.6%, respectively. The Korean elderly were co-exposed to DEHP and DnBP, and the variation of DEHP and DnBP metabolite levels was mainly attributed to intra-individual variation, rather than inter-individual variation. Furthermore, Korean elderly were exposed to the hazards of DEHP and DnBP based on the high level of the exceedance rate over TDI or RfD for DEHP and DnBP. Since the elderly are very susceptible to environmental pollutants, the harmful effects of DEHP and DnBP in the elderly population should be further studied in the future.

[en] Highlights: • Bisphenol-A exposure restricts intrauterine length growth. • Intrauterine growth was affected by maternal glutathione transferase polymorphism. • But neonatal Bisphenol-A exposure increases the postnatal volume growth. • Child growth was affected by infant sex. We aimed to evaluate the effects of Bisphenol-A (BPA) exposure on fetal/child growth from the fetal period to 72 months after birth. The MOCEH study is a prospective birth cohort study in Korea. A total of 788 mother-child pairs in the third trimester and 366 pairs in the neonatal period who completed BPA assessment and fetal/children growth outcomes were included. BPA assessments were conducted twice in the third trimester using maternal urines and the neonatal period using neonatal urines. Fetal femur length was measured with ultrasound, and estimated-fetal-weight was calculated. Child growth outcomes including three z-scores for age-specific length, weight-for-length (WFL) and weight were calculated. Analysis was performed according to infant sex and maternal glutathione transferases (GSTs) polymorphisms. When maternal urinary BPA concentration in the third trimester increased by 1 log-transformed unit of BPA/Cr, the third trimester femur length decreased 0.03(0.01) cm in the whole and 0.06(0.02) cm in the GSTM1/GSTT1 either null group. Then, maternal urinary BPA levels and birth outcomes were positively correlated. When the prenatal BPA concentration is increased by 1 log-transformed unit of BPA/Cr, the z-score for weight at birth increased 0.05(0.02) in whole and 0.06(0.03) in boys and the z-score for WFL at birth increased 0.05(0.02) in whole and 0.07(0.03) in girls. In linear mixed models, significant positive effects of the neonatal urinary BPA were found on WFL over the 72 months period. When the neonatal BPA concentration is increased by 1 log-transformed unit of BPA concentration, the z-score for weight through 6–72 months increased 0.09(0.03) in whole and 0.12(0.05) in girls. Our study suggests BPA exposure is negatively associated with intrauterine linear growth, but has a positive association with volume growth during childhood. Furthermore, intrauterine growth was affected by maternal GSTs polymorphism, and child growth was affected by sex.