ABSTRACT
Purpose@#Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients. @*Materials and Methods@#Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model. @*Results@#We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression. @*Conclusion@#This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.
ABSTRACT
Purpose@#Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients. @*Materials and Methods@#Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model. @*Results@#We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression. @*Conclusion@#This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.
ABSTRACT
MicroRNAs (miRNAs), which play a role in tumorigenesis, may also serve as diagnostic or prognostic biomarkers. However, studies on human miRNA profiles in plasma from nasopharyngeal carcinoma (NPC) patients are in their infancy. Here, we used microarrays to perform systematic profiling of human miRNAs in plasma from NPC patients. We subsequently used real-time quantitative polymerase chain reaction (Q-PCR) to validate miRNAs with aberrant expression that could serve as potential biomarkers. By comparing the plasma miRNA profiles of 31 NPC patients and 19 controls, 39 of 887 human miRNAs were found to be aberrantly expressed. Considering the fold change and P value, miR-548q and miR-483-5p were validated in 132 samples from 82 NPC patients and 50 controls. Moreover, high expression of miR-548q and miR-483-5p was further found in 3 NPC cell lines and clinical biopsy tissues from 54 NPC patients and 22 controls. Our results revealed that miR-548q and miR-483-5p are potential biomarkers of NPC. Combining the receiver operating characteristic (ROC) analyses of these 2 miRNAs, an area under the ROC curve (AUC) of 0.737 with 67.1% sensitivity and 68.0% specificity were obtained, showing the preliminary diagnostic value of plasma miRNAs. Moreover, most NPC patients with a poor outcome exhibited high expression (> median) of miR-548q (70.6%) and miR-483-5p (64.7%) in tissue samples, indicating their prognostic value. The high expression levels of miR-548q and miR-483-5p in plasma, cell lines, and clinical tissues of NPC patients indicate that their roles in NPC should be explored in the future.
Subject(s)
Aged , Humans , Biomarkers , Carcinoma , MicroRNAs , Nasopharyngeal Neoplasms , Plasma , Prognosis , Real-Time Polymerase Chain Reaction , Sensitivity and SpecificityABSTRACT
Objective To assess the impact of tea consumption on the risk of osteoporotic hip fractures.Methods Between January 2008 and June 2012,581 (148 males,433 females) incident cases of hip fractures were enrolled from four hospitals in Guangdong province,with 581 sex-and age-matched (± 3 years) controls from either hospitals or communities.Face-to-face interviews wer conducted to collect data pertaining to tea drinking and various covariates.Results Results from univariate conditional logistic analyses showed that an inverse association was observed in tea drinking and hip fracture risk.Longer time,greater frequency and dosage of tea consumption were dose-dependently associated with lower risk of hip fractures (P-trend ＜0.05).Compared to non drinkers,the odd ratios related to regular tea drinkers,subgroups with different length,frequency,dosage,type of tea consumption were ranged between 0.54 and 0.74 (all P＜0.05).After adjustment for factors as age,daily energy intake,BMI,education levels,passive smoking,calcium supplement and physical activity,the dose-dependent associations among above said factors still remained significant.However,the strength of the association lowered slightly.The beneficial effect of tea was significant only in men but not in women.Similar effects were found in subjects with different education levels.Conclusion Regular tea drinking habit might decrease the risk of osteoporotic hip fractures in the elderly males.
ABSTRACT
Objective To assess the relationship between cardiovascular risk factors and osteoporosis. Methods 2202 women aged 50-73 years were included in this cross-sectional study from the communities in Guangzhou, from July 2008 to January 2010. Cardiovascular risk factors including age, years since menopause, physical activity, anthropometrics, body composition, blood pressure, fasting serum lipids, glucose and uric acid, intima-media thickness(IMT) of carotid artery were assessed. Ultrasonic bone density (speed of sound) at the radius and tibia were determined. Osteoporosis was defined as T-score≤-2.5. Common factors for the cardiovascular risk factors were extracted using the factor analysis method. Results Eight common factors representing obesity, lean mass, blood triglycerides and uric acid, cholesterol, age, blood pressure, IMT and physical activity were extracted. Data from the Multivariate logistic regression showed a dose-dependent association of greater scores of age and IMT factors and lower score of lean mass factor with the increased risk of osteoporosis at the radius and tibia. As compared with the bottom quartile, the OR (95%CI) of radius and tibia osteoporosis were 0.62 (0.44-0.88) and 0.62 (0.48-0.80) for lean mass factor, 4.02 (2.72-5.94) and 3.68(2.81-4.82) for age factor, 1.41 (1.00-2.00) and 1.54 (1.19-2.00) for IMT factors, respectively. Moreover, greater blood pressure score was associated with higher risk of radius osteoporosis while the higher obese score, was correlated with the increased risk of tibia osteoporosis. Conclusion The cardiovascular-related risk factors of greater IMT, obesity, blood pressure and lower lean mass scores were associated with increased osteoporosis risks while called for more concern among the Chinese women.