No significant association between the XRCC3 Thr241Met polymorphism and lung cancer risk: a meta-analysis.

The development of lung cancer is significantly associated with genetic susceptibility. Findings from previous individual studies regarding the effect of X-ray repair cross-complementing group 3 Thr241Met (XRCC3 Thr241Met) polymorphism on lung cancer risk remained conflicting and inconclusive. Thus, a meta-analysis of previous relevant studies was performed to estimate this effect more precisely and to shed some light on the contradictory findings. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the correlation of XRCC3 Thr241Met polymorphism with lung cancer susceptibility. Stratified analysis according to ethnicity and sensitivity analysis was both conducted for further confirmation. Seventeen independent case-control studies involving 12,610 subjects totally were included into this meta-analysis. Overall, meta-analysis of total included studies showed that the XRCC3 Thr241Met polymorphism was not associated with risk of lung cancer in all genetic contrast models (OR Met allele vs. Thr allele = 1.01, 95 % CI 0.91-1.13, P OR = 0.810; OR Met/Met vs. Thr/Thr = 1.16, 95 % CI 0.88-1.54, P OR = 0.281; OR Thr/Met vs. Thr/Thr = 0.95, 95 % CI 0.86-1.04, P OR = 0.240; OR Met/Met + Thr/Met vs. Thr/Thr = 0.97, 95 % CI 0.89-1.06, P OR = 0.538; OR Met/Met vs. Thr/Thr + Thr/Met = 1.18, 95 % CI 0.91-1.52, P OR = 0.204). Stratified analyses in Asians and Caucasians showed similar results. Sensitivity analysis confirmed the stability and reliability of the findings. This meta-analysis of all available data did not support any appreciable association between the XRCC3 Thr241Met polymorphism and lung cancer risk in any populations.

Clinical analysis of postoperative venous thromboembolism risk factors in lung cancer patients.

BACKGROUND AND OBJECTIVES: The objective of this study is to explore clinical risk factors for venous thromboembolism (VTE) in postoperative lung cancer patients in order to provide a basis for the prevention and treatment of postoperative VTE. METHODS: A total of 1,001 lung cancer patients were retrospectively analyzed. Each patient was confirmed with surgical pathology diagnosis and had a complete clinical and follow-up record. VTE was identified in a combination of spiral computed tomography (CT), pulmonary angiography, and color Doppler ultrasound. We used life table method to create an occurrence frequency curve of thrombosis. We also searched for high risk factors for postoperative VTE with Cox multivariate regression model and created frequency curves of thrombosis against different risk factors using Kaplan-Meier method. RESULTS: As of July 31, 2011, the median follow-up time is 25.73 ± 0.11 months (19.23-31.37). The cumulative frequency of VTE among 1,001 lung cancer patients is 2%, 3%, 4%, 5%, and 5.3% over 1, 3, 6, 12, and 30 months after the surgery. COX regression analysis showed that the hazard ratio of VTE occurrence in patients with incomplete resection relative to ones with complete resection is 9.867 (95% CI: 5.275-18.459, P = 0.000). And the hazard ratio of VTE occurrence is 3.472 (95% CI: 1.761-6.845, P = 0.000) in patients with anti-angiogenesis treatment compared to patients without such treatment. The hazard ratio of VTE occurrence is 2.808 (95% CI: 1.439-5.479, P = 0.002) in patients with EGFR-TKI treatment relative to patients without the treatment, and 7.520 (95% CI: 3.968-14.250, P = 0.000) in patients with an increase in D-dimer level relative to normal ones CONCLUSIONS: The highest incidence of VTE is within 1 month after lung cancer surgery. High risk factors for VTE include incomplete surgical resection, postoperative use of anti-angiogenesis drugs, EGFR-TKI application and an increase in preoperative D-dimer level.

[Short-term intermittent prophylactic administration of recombinant human thrombopoietin attenuates chemotherapy-induced thrombocytopenia in lung cancer patients].

OBJECTIVE: To evaluate the efficacy of short-term intermittent prophylactic use of a recombinant human thrombopoietin (rhTPO) in chemotherapy-induced severe thrombocytopenia in lung cancer patients. METHODS: 24 advanced non-small cell lung cancer (NSCLC) patients who experienced severe thrombocytopenia in the last chemotherapy cycle received prophylactic rhTPO treatment in the next chemotherapy cycle (prophylactic treated cycle, PTC). rhTPO was given subcutaneously 300 U×kg(-1)×d(-1) on days 2, 4, 6, and 9 after the initiation of chemotherapy. Platelet count was monitored and compared with that in the previous treatment cycle (control cycle, CC). RESULTS: The lowest platelet count in the prophylactic rhTPO cycle was significantly higher than that in control cycle [(56 ± 16) × 10(9)/L vs. (28 ± 13) × 10(9)/L, P < 0.001]. The duration of thrombocytopenia was also shortened by the prophylactic rhTPO [(8 ± 2) d vs. (12 ± 3) d, P < 0.001]. The area under curve (AUC) of platelet count (21 days) was significantly increased [(3517 ± 685) × 10(9)/L vs. (2063 ± 436) × 10(9)/L, P < 0.001]. The time to platelet nadir and peak was not affected. CONCLUSION: Prophylactic use of rhTPO can attenuate the severity and shorten the duration of chemotherapy-induced thrombocytopenia in lung cancer patients.

[Incidence, time trend, survival, and predictive factors of lung cancer in Shanghai populations].

OBJECTIVE: To investigate the incidence, survival, and influential factors of lung cancer in the Shanghai populations. METHODS: Data of individual cases of lung cancer 2000 - 2004 were obtained from the Shanghai Cancer registry System. The annual prevent change (APC) of incidence of lung cancer from 1972 to 2004 was calculate by crude and standardized rates so as to analyze the time trends. Cox proportional risk model was used to analyze the factors influencing the survival. RESULTS: 23,196 new cases of lung cancer were diagnosed 2002 - 2004. The crude incidence rate of lung cancer in the females was 33.73/100,000, and the age-adjusted rate was 30.90/100,000. The crude incidence rate of lung cancer and the age-adjusted rate for the males were 81.65/100,000 and 33.73/100,000 respectively, both higher than those of females. The APC values of crude incidence 2004 for both the males and females increased by 1.723% and 2.036% respectively in comparison with the values 1972 (both P < 0.01). The age-adjusted APC of standardized incidence rate for the males in the city center was -0.605% (P < 0.01), showing a tendency to reduce; while the age-adjusted APC of standardized incidence rate for the females in the city center was -0.136 (P > 0.05). The proportion of stage IV cases in the females was 47.5%, significantly higher than that in the males (40.0%, P < 0.05). The proportion of adenocarcinoma in the females was 86.1%, significantly higher than that in the males (47.8%, P < 0.05). The 3-year survival rate and median survival time of adenocarcinoma in the females were 30.38% and 1.48 years respectively, both significantly higher than those in the males (22.66% and 0.98 years, both P < 0.01). Female gender, being younger, living in urban area, squamous cancer, early stage, visit to higher-grade hospital were the factors beneficial to the prognosis of lung cancer. CONCLUSION: The age adjusted incidence rate of lung cancer in Shanghai is much closer to that of Western Europe and North America. The beneficial factors for higher survival rate are female, younger age, urban residency, squamous cell lung cancer, earlier stage of diagnosis, and higher grade hospital for treatment. Women have statistically better outcomes than men in different stages of disease.

XBP1-LOX Axis is critical in ER stress-induced growth of lung adenocarcinoma in 3D culture.

Rapid growth of tumor cells needs to consume large amounts of oxygen and glucose, due to lack of blood supply within the tumor, cells live in an environment that lack of oxygen and nutrients. This environment results in endoplasmic reticulum (ER) stress and activates the UPR (unfolded protein response). More and more evidence suggests UPR provides a growth signal pathway required for tumor growth. In the present study, we investigated the relationship between XBP1, one transcription factor in UPR, and the expression of LOX. We found that ER stress induces high expression of XBP1, one transcription factor in UPR, in both 2D culture and 3D culture; but only promotes growth of lung adenocarcinoma cells in in vitro 3D culture other than 2D culture. In 3D culture, we further showed that knockdown XBP1 expression can block Tm/Tg-induced cell growth. LOX genes may be key downstream effector of XBP1. Knockdown LOX expression can partially block XBP1-induced cell growth. Then we showed XBP1 suppressed by RNA interference (RNAi) can reduce the expression of LOX. For the first time, it is being shown that XBP1 can regulate the expression of LOX to promote cell growth.