Influence of Hospice Palliative Care on Medical Service Usage in Prolonged Mechanical Ventilation Cases: A Nationwide Cohort Study.

BACKGROUND: Numerous studies have demonstrated that hospice palliative care interventions for cancer patients can reduce health care utilzation. In Taiwan, 20-25% of patients who require mechanical ventilation are using prolonged mechanical ventilation (PMV); however, only a limited number of studies have addressed the effectiveness of hospice palliative care for these patients. This study investigated the impact of hospice palliative care utilization on medical utilization among subjects using PMV. METHODS: By using the health insurance database of a nationwide population-based study, we identified subjects who had been on mechanical ventilation for > 21 d, were age ≥18 y between 2009 and 2017, and had received hospice palliative care. The control group was formed through 1:1 matching by using propensity scoring after excluding patients who had participated in palliative care for <15 d or for >181 d. Furthermore, we used a conditional logistic regression analysis to investigate the incidence of ICU admission, emergency department presentation, and cardiopulmonary resuscitation within 14 d before death. RESULTS: A total of 186,533 new subjects receiving PMV age ≥ 18 y were admitted between 2009 and 2017. In addition, the number of subjects receiving palliative care increased annually, rising from 0.6% in 2009 to 41.33% in 2017. The emergency department visits (odds ratio [OR] 0.68, 95% CI 0.63-0.74), ICU admission (OR 0.59, 95% CI 0.53-0.66), cardiopulmonary resuscitation (OR 0.40, 95% CI 0.35-0.46), and total hospitalization cost ($1,319.91 ± $1,821.66 versus $1,544.37 ± $2,309.27 [$USD], P < .001) were significant lower in the palliative care group. CONCLUSIONS: Subjects undergoing PMV while receiving hospice palliative care experienced significant reductions in total hospitalization costs, ICU admissions, cardiopulmonary resuscitation, and medical expenses within 14 d before death.

Stress on caregivers providing prolonged mechanical ventilation patient care in different facilities: A cross-sectional study.

PURPOSE: Taiwan has implemented an integrated prospective payment program (IPP) for prolonged mechanical ventilation (PMV) patients that consists of four stages of care: intensive care unit (ICU), respiratory care center (RCC), respiratory care ward (RCW), and respiratory home care (RHC). We aimed to investigate the life impact on family caregivers of PMV patients opting for a payment program and compared different care units. METHOD: A total of 610 questionnaires were recalled. Statistical analyses were conducted by using the chi-square test and multivariate logistic regression model. RESULTS: The results indicated no associations between caregivers' stress levels and opting for a payment program. Participants in the non-IPP group spent less time with friends and family owing to caregiver responsibilities. The results of the family domain show that the RHC group (OR = 2.54) had worsened family relationships compared with the ICU group; however, there was less psychological stress in the RCC (OR = 0.54) and RCW (OR = 0.16) groups than in the ICU group. In the social domain, RHC interviewees experienced reduced friend and family interactivity (OR = 2.18) and community or religious activities (OR = 2.06) than the ICU group. The RCW group felt that leisure and work time had less effect (OR = 0.37 and 0.41) than the ICU group. Furthermore, RCW interviewees (OR = 0.43) were less influenced by the reduced family income than the ICU group in the economic domain. CONCLUSIONS: RHC family caregivers had the highest level of stress, whereas family caregivers in the RCW group had the lowest level of stress.

A Meta-analysis of Dynamic Prevalence of Cognitive Deficits in the Acute, Subacute, and Chronic Phases After Traumatic Brain Injury.

ABSTRACT: BACKGROUND: Reports regarding prevalence of post-traumatic brain injury (TBI) cognitive deficits were inconsistent. We aimed to synthesize the prevalence of cognitive deficits after TBI in the acute, subacute, and chronic phases. METHODS: PubMed, EMBASE, and ProQuest Dissertations and Theses A&I databases were searched from the inception to April 27, 2020. Studies with prospective, retrospective, and cross-sectional designs reporting the prevalence of cognitive deficits after TBI in adults were included. RESULTS: A total of 15 articles were included for prevalence estimation. The pooled prevalence of memory and attention deficits after mild TBI was 31% and 20% in the acute phase and 26% and 18% in the subacute phase, respectively, and 49% and 54% in the subacute phase and 21% and 50% in the chronic phase after moderate-to-severe TBI. The overall prevalence of information processing speed deficits after mild TBI in the acute and subacute phases was 21% and 17%, respectively, and 57% in the chronic phase after moderate-to-severe TBI. The overall prevalence of executive dysfunction in the subacute and chronic phases was 48% and 38%, respectively, after moderate-to-severe TBI. CONCLUSION: Cognitive deficits are prevalent in the acute to chronic phases after TBI. Healthcare providers should design effective intervention targeting cognitive impairment after TBI as early as possible.

Effect of the Integrated Prospective Payment Program on Family Members' Knowledge and Acceptance of Hospice Care of Patients on Prolonged Mechanical Ventilation.

BACKGROUND: We sought to evaluate the effect of an integrated prospective payment program (IPP) on knowledge of hospice care and willingness to participate in hospice care among family members of patients on prolonged mechanical ventilation (PMV). METHODS: Between November 2013 and April 2014, we used paper-based survey questionnaires from 64 institutions to evaluate knowledge, willingness, and related factors among the main caregivers of patients on PMV regarding hospice care and to determine whether their decisions for the patients were affected by the IPP. RESULTS: The average ages of the respondents and patients on PMV were 51.9 y and 70.8 y respectively; 70.6% of the respondents knew about the Hospice Palliative Care Act (HPCA), and 42.3% of the medical staff had introduced hospice care-related information to patients and caregivers in Taiwan. Among the caregiver respondents, 67.6% agreed to write a letter of intent regarding the choice of hospice care or limited life-sustaining treatment. In total, 66.2% (16.1 + 50.1%) of the respondents agreed to hospice care for their family members (ie, the patients on PMV) when the condition was terminal. The factors of greater HPCA knowledge among the patients on PMV were IPP participation, female sex, and coma status. Factors leading to higher levels of HPCA knowledge included age ≥ 65 y being married, higher income, awareness of the law, and being introduced to hospice care by medical staff. CONCLUSIONS: High levels of hospice care knowledge were unrelated to willingness to participate. HPCA knowledge was greater in the IPP group than in the non-IPP group; however, there was no significant difference in the willingness to agree to hospice care. It is recommended that individuals be encouraged to express their medical decisions.

Is incentive spirometry beneficial for patients with lung cancer receiving video-assisted thoracic surgery?

BACKGROUND: The effectiveness of Incentive spirometry (IS) in patients undergoing video-assisted thoracic surgery (VATS) remains lacking. We conducted a population-based study to investigate the effectiveness of IS on patients with lung cancers following VATS. METHODS: We identified patients newly diagnosed with lung cancer who underwent surgical resection by VATS or thoracotomy from the years 2000 to 2008 in the Longitudinal Health Insurance Database. Exposure variable was the use of IS during admission for surgical resection by VATS or thoracotomy. Primary outcomes included hospitalization cost, incidence of pneumonia, and length of hospital stay. Secondary outcomes included the frequency of emergency department (ED) visits and hospitalizations at 3-month, 6-month, and 12-month follow-ups after thoracic surgery. RESULTS: We analyzed 7549 patients with lung cancer undergoing surgical resection by VATS and thoracotomy. The proportion of patients who were subjected to IS was significantly higher in those who underwent thoracotomy than in those who underwent VATS (68.4% vs. 53.1%, P < 0.0001). After we controlled for potential covariates, the IS group significantly reduced hospitalization costs (- 524.5 USD, 95% confidence interval [CI] = - 982.6 USD - -66.4 USD) and the risk of pneumonia (odds ratio = 0.55, 95% CI = 0.32-0.95) compared to the non-IS group following VATS. No difference in ED visit frequency and hospitalization frequency at 3-month, 6-month, and 1-year follow-up was noted between the IS and the non-IS groups following VATS. CONCLUSIONS: The use of IS in patients with lung cancers undergoing VATS may reduce hospitalization cost and the risk of pneumonia.

Propensity score-matching analyses on the effectiveness of integrated prospective payment program for patients with prolonged mechanical ventilation.

OBJECTIVES: An integrated delivery system with a prospective payment program (IPP) for prolonged mechanical ventilation (PMV) was launched by Taiwan's National Health Insurance (NHI) due to the costly and limited ICU resources. This study aimed to analyze the effectiveness of IPP and evaluate the factors associated with successful weaning and survival among patients with PMV. METHODS: Taiwan's NHI Research Database was searched to obtain the data of patients aged ≥17 years who had PMV from 2006 to 2010 (N=50,570). A 1:1 propensity score matching approach was used to compare patients with and without IPP (N=30,576). Cox proportional hazards modeling was used to examine the factors related to successful weaning and survival. RESULTS: The related factors of lower weaning rate in IPP participants (hazard ratio [HR]=0.84), were older age, higher income, catastrophic illness (HR=0.87), and higher comorbidity. The effectiveness of IPP intervention for the PMV patients showed longer days of hospitalization, longer ventilation days, higher survival rate, and higher medical costs (in respiratory care center, respiratory care ward). The 6-month mortality rate was lower (34.0% vs. 32.9%). The death risk of IPP patients compared to those non-IPP patients was lower (HR=0.91, P<0.001). CONCLUSIONS: The policy of IPP for PMV patients showed higher survival rate although it was costly and related to lower weaning rate.

Factors Associated With Re-Intubation Within 14 Days After Ventilator Liberation.

BACKGROUND: According to Taiwan's integrated delivery system policy, ventilator-dependent patients are successfully liberated from mechanical ventilation in accordance with step-down care. However, premature discharge affects the 14-d readmission quality index. Therefore, we explored the risk and related factors of subjects liberated from mechanical ventilation who were re-intubated within 14 d. METHODS: This retrospective study analyzed a cohort of ventilator-dependent subjects 17 y of age and older using a population-based database from the Taiwan National Health Research Institutes Database from 2006 to 2010. Chi-square test and logistic regression analyses were used to explore whether subjects liberated from mechanical ventilation were re-intubated within 14 d and to investigate the related factors. RESULTS: A total of 15,840 ventilator-dependent subjects were liberated from mechanical ventilation, and 449 subjects were re-intubated within 14 d; the total re-intubation rate was 2.83%. The factors related to a higher risk of re-intubation were also the reasons for ventilator use, including complications, hospital accreditation level, and the ventilator weaning care stage. A higher risk of re-intubation was identified in subjects with COPD (odds ratio [OR] 1.32, 95% CI 1.02-1.7, P = .035) or pneumonia (OR 1.4, 95% CI 1.07-1.86, P = .02) and in subjects who stayed at a district hospital (OR 3.53, 95% CI 2.48-5.01, P < .001). Liberation from mechanical ventilation in the respiratory care ward and home respiratory care were associated with the highest risk of re-intubation, which was 2.32 times that of ICU subjects (P < .001). CONCLUSIONS: Factors associated with re-intubation within 14 d after ventilator liberation are related to the level and quality of the care setting; thus, to prevent re-intubation, more attention should be paid to higher-risk ventilator-dependent subjects after they are liberated from mechanical ventilation.

The Contribution of Interleukin-10 Promoter Genotypes to Susceptibility to Asthma in Adults.

AIM: Accumulating evidence suggests that inflammatory processes play a role in asthma etiology, and interleukin-10 (IL10) is an important immunosuppressive cytokine. The present study aimed to evaluate the contribution of IL10 promoter A-1082G (rs1800896), T-819C (rs3021097), A-592C (rs1800872) genetic polymorphisms to the risk of asthma in Taiwan. MATERIALS AND METHODS: Associations of three IL10 polymorphic genotypes with risk of asthma were investigated among 198 patients with asthma and 453 non-asthmatic healthy controls, by polymerase chain reaction-restriction fragment length polymorphism genotyping method. RESULTS: The results showed that the percentages of TT, TC and CC for IL-10 T-819C genotypes were differentially represented at 63.1%, 32.3% and 4.6%, respectively, in the patient group and 53.0%, 36.4% and 10.6%, respectively, in the healthy control group (p for trend=0.0114). The CC genotype carriers were at lower risk for asthma (odds ratio=0.36, 95% confidence interval=0.17-0.76, p=0.0055). There was no difference in the distribution of A-1082G or A-592C genotype between the asthma and non-asthma groups. The protective effects of the CC genotype were obvious among males, but not females, and those aged 25 up to 40 years but not those aged over 40 years. CONCLUSION: The CC genotype of IL10 T-819C compared to the TT genotype may have a protective effect on asthma risk in younger adults (25-40 years old), and males in Taiwan.

The Risk and Related Factors for Readmission to an ICU Within 7 Days in Mechanically Ventilated Subjects--A Nationwide Population-Based Cohort Study.

BACKGROUND: Readmission of mechanically ventilated patients to an ICU within 7 d reflects not only patient safety but also the quality of care of the ICU. This study aimed to investigate the risk and related factors for readmission to an ICU within 7 d in mechanically ventilated subjects. METHODS: A total of 658,452 mechanically ventilated subjects discharged from an ICU whose age was ≥ 17 y old were obtained from the Taiwan National Health Insurance Research Database for the period from January 1, 2005, to December 31, 2011. The study applied a generalized estimating equation logistic regression model to explore whether the mechanically ventilated subjects were readmitted within 7 d or not and the related factors. RESULTS: A total of 29,657 subjects were readmitted to the ICU within 7 d; the total readmission rate was 4.5%. Also, 64.8% of the subjects with the same diagnosis were returned to the ICU within 7 d. Generalized estimating equation logistic regression model results showed that the factors related to higher risk of readmission were male sex, old age, higher comorbidity score, complications (eg, pneumothorax, subcutaneous emphysema, pneumonia, oxygen toxicity, pulmonary embolism, or pulmonary edema), use of a private hospital ICU, ICU stay ≥21 d, transfer to a respiratory care center and respiratory care ward, and subsequent transfer to the regional hospital or district hospital. CONCLUSIONS: The risk and related factors of a mechanically ventilated subject whose age is ≥ 17 y old being readmitted to the ICU within 7 d include subject characteristics, health status, hospital attributes, and the length of ICU stay. Therefore, higher risk subjects should receive attention and assessment before transfer or discharge from the ICU to prevent readmission.

Association of inflammatory bowel disease with asthma risk: A nationwide cohort study.

OBJECTIVE: We evaluated the risk of asthma development in adult patients with inflammatory bowel disease (IBD) in a nationwide population. METHODS: A retrospective cohort study was conducted by using data retrieved from the Taiwan National Health Insurance Research Database. Patients, ages 20 year or older, with newly diagnosed IBD between 2000 and 2005 were identified and randomly frequency-matched (based on sex, age, and index year) with four times the number of enrollees without IBD from the general population. Both cohorts were followed up until the end of 2011 to examine the incidence of asthma. Cox proportional hazard regression analysis was used to measure the hazard ratios (HR) of asthma in the IBD cohort compared with that in the non-IBD cohort. RESULTS: The IBD and non-IBD cohorts comprised 5260 patients with IBD and 21,040 participants, respectively. After adjustment for covariates, the IBD cohort exhibited a 1.50-fold increased risk for asthma (HR 1.50, [95% confidence interval {CI}, 1.32-1.71]). Further analysis according to the two major forms of IBD revealed that the adjusted HR of asthma was 1.46 (95% CI, 1.03-2.07) and 1.50 (95% CI, 1.31-1.72) in patients with ulcerative colitis and Crohn's disease, respectively, compared with the non-IBD cohort. CONCLUSION: After adjustment for comorbidities, patients with IBD were associated with a higher subsequent risk of asthma.

Association between obstructive sleep apnea and deep vein thrombosis / pulmonary embolism: a population-based retrospective cohort study.

BACKGROUND: Obstructive sleep apnea (OSA) is a major contributor to cardiovascular disease, and may cause severe morbidity and mortality. Recent studies have indicated that OSA patients exhibited elevated platelet activity, fibrinogen levels, and platelet aggregation. OBJECTIVES: We investigated the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients diagnosed with OSA compared with age- and sex-matched unaffected people. PATIENTS/METHODS: This longitudinal, nationwide, population-based cohort study was conducted using data from Taiwan National Health Insurance Research Database (NHIRD) recorded between January 2000 and December 2011. The study consisted of 3511 patients with OSA and 35110 matched comparison individuals. A Cox proportional hazard regression was used to compute the risk of DVT and PE in patients with OSA compared with those without OSA. RESULTS: The DVT and PE risks were 3.50- and 3.97-fold higher (95% CI=1.83-6.69 and 1.85-8.51) respectively, in the OSA cohort than in the reference cohort after we adjusted for age, sex, and comorbidities. CONCLUSION: This nationwide population-based cohort study indicates that patients with OSA exhibit a higher risk of subsequent DVT and PE.

Impact of Taiwan's integrated prospective payment program on prolonged mechanical ventilation: a 6-year nationwide study.

OBJECTIVE: The integrated prospective payment program (IPP), which encourages the integrated care of mechanically ventilated patients in order to reduce the heavy utilization of high-cost ICUs, has been implemented by Taiwan's Bureau of National Health Insurance since July 2000. The aim of this study was to assess the impact of this program on weaning, hospital stay, mortality, and cost for patients requiring prolonged mechanical ventilation (PMV). METHODS: A data set of 1,000,000 randomly selected insurance holders from the National Health Research Insurance Database, Taiwan, was retrospectively analyzed. We enrolled 7,967 adult patients (age ≥ 17 y) who required PMV (duration ≥ 21 d) over a 6 year period. RESULTS: There were 3,275 patients on PMV before (1997-1999) and 4,692 patients on PMV after (2001-2003) the IPP implementation. After IPP implementation, PMV was found to be required in patients with a significantly higher age, lower urbanization level, higher income status, and a higher prevalence of neuromuscular disease (P < .001). In-hospital mortality was similar between the 2 periods (17.2% before vs 16.2% after, P = .26), but the weaning rate was significantly lower in the latter period (68.1% vs 64.2%, P < .001). Total hospital stay (75.3 d vs 95.1 d, P < .001) and duration of mechanical ventilation usage (55.8 d vs 71.6 d, P < .001) were both significantly higher after the IPP implementation. Total hospitalization cost in the PMV patients was significantly lower after IPP implementation. CONCLUSIONS: Implementation of the IPP program reduced the total hospitalization cost, increased the duration of mechanical ventilation usage and stay, and reduced the weaning rate in PMV patients.

Association of DNA double-strand break gene XRCC6 genotypes and lung cancer in Taiwan.

AIM: The DNA repair gene X-ray repair complementing defective repair in Chinese hamster cells 6 (XRCC6) is thought to play an important role in the repair of DNA double-strand breaks. It is known that defects in double-strand break repair capacity can lead to irreversible genomic instability. However, the association of polymorphic variants of XRCC6 with lung cancer susceptibility has never been reported. In this hospital-based case-control study, the association of XRCC6 promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter G-31A (rs132770), and intron 3 (rs132774) polymorphisms with lung cancer risk in a Taiwanese population, was studied. MATERIALS AND METHODS: In total, 358 patients with lung cancer and 716 healthy controls recruited from the China Medical Hospital in Taiwan were genotyped. RESULTS: The results showed that there were significant differences between lung cancer and control groups in the distribution of their genotypic (p=3.7×10(-4)) and allelic frequency (p=2.7×10(-5)) in the XRCC6 promoter T-991C polymorphism. Individuals who carried at least one C allele (TC or CC) had a 2.03-fold increased odds ratio of developing lung cancer compared to those who carried the wild-type TT genotype (95% conference internal=1.42-2.91, p=0.0001). For the other three polymorphisms, there was no difference between the case and control groups in the distribution of either genotypic or allelic frequency. CONCLUSION: In conclusion, the XRCC6 promoter T-991C, but not the promoter C-57G, promoter G-31A or intron 3, is associated with lung cancer susceptibility.

Interaction of CCND1 genotype and smoking habit in Taiwan lung cancer patients.

AIM: Cyclin D1 (CCND1) is critical in the transition of the cell cycle from G1 to S phase and unbalanced cell cycle regulation is a hallmark of carcinogenesis. The study aimed at investigating the association of CCND1 genotypes with lung cancer risk in Taiwan and examining the interaction between CCND1 genotype and smoking habit. PATIENTS AND METHODS: CCND1 A870G (rs9344) and C1722G (rs678653) genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis of DNA from the blood of 358 lung cancer patients and 716 cancer-free healthy controls. RESULTS: The results showed that there were significant differences between lung cancer and control groups in the distribution of the genotypes (p=0.0003) and allelic frequency (p=0.0007) in the CCND1 rs9344 genotype. Individuals who carried AG or GG genotype had 0.59- and 0.52-fold risk, respectively, of developing lung cancer compared to those who carried the AA genotype (95% CI=0.44-0.78 and 0.35-0.79, respectively). There was also an obvious interaction of CCND1 rs9344 genotype with personal smoking habit on lung cancer risk (p=0.0009). CONCLUSION: These findings support the conclusion that cell cycle regulation may play a role in lung cancer development and that CCND1 rs9344 polymorphism together with smoking habit maybe a useful biomarker for lung cancer prediction.

The joint effect of hOGG1 single nucleotide polymorphism and smoking habit on lung cancer in Taiwan.

AIM: To evaluate the association and interaction among human 8-oxoguanine DNA glycosylase 1 (hOGG1) genotypic polymorphism, smoking status and lung cancer risk in Taiwan. MATERIALS AND METHODS: The gene for hOGG1 was analyzed via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 358 patients with lung cancer and 716 healthy controls recruited from the China Medical Hospital. RESULTS: The hOGG1 codon 326 genotypes were not differently distributed between the lung cancer and control groups (p=0.0809). However, the C allele of hOGG1 codon 326 was significantly (p=0.0198) more frequently found in controls than in cancer patients. We further analyzed the joint effect of genetics and smoking on lung cancer risk and found an interaction between hOGG1 codon 326 genotypes and smoking status. The hOGG1 codon 326 C allele-bearing genotypes were significantly associated with lung cancer risk only in the smoker group (p=0.0132), but not in the non-smoker group (p=0.06588). CONCLUSION: Our results provide evidence that the C allele of hOGG1 codon 326 may have a joint effect with smoking on the development of lung cancer.

Interaction of cyclooxygenase 2 genotype and smoking habit in Taiwanese lung cancer patients.

AIM: The aim of this study was to evaluate the association and interaction of genotypic polymorphisms in the cyclooxygenase 2 (Cox-2) gene with smoking habits with lung cancer patients in Taiwan. Six polymorphic variants of Cox-2 were analysed in association with their effect on lung cancer susceptibility, and their joint effects with smoking habits on lung cancer risk is discussed. MATERIALS AND METHODS: Three hundred and fifty-eight patients with lung cancer and 716 healthy controls from the China Medical Hospital in central Taiwan were genotyped. RESULTS: The Cox-2 intron 6 (rs2066826) genotypes were distributed differently between the lung cancer and control groups. The A allele of Cox-2 intrin 6 was found more frequently in the cancer patient group than in the controls. Furthermore, the interactions of smoking with genetic factors were significant for the Cox-2 intron 6 genotypes. Patients who smoked and had the Cox-2 intron 6 AG or AA genotype had an increased risk of 2.21 (95% confidence interval=1.53-3.27) for developing lung cancer. CONCLUSION: These results provide evidence that the A allele of Cox-2 intron 6 may be associated with the development of lung cancer and may be a useful marker for early detection and treatment of lung cancer.

Interaction of methylenetetrahydrofolate reductase genotype and smoking habit in Taiwanese lung cancer patients.

UNLABELLED: The aim of this study was to evaluate the association and interaction of genotypic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and environmental factors with lung cancer in Taiwan. Two well-known polymorphic variants of MTHFR, C677T (rs1801133) and A1298C (rs1801131), were analyzed in association with lung cancer susceptibility, and discussed their joint effects with individual habits on lung cancer risk. PATIENTS AND METHODS: In total, 358 patients with lung cancer and 716 healthy controls recruited from the China Medical Hospital in central Taiwan were genotyped. RESULTS: The MTHFR C677T genotype, but not the A1298C, was differently distributed between the lung cancer and control groups. The T allele of MTHFR C677T was significantly more frequently found in controls than in cancer patients. As for A1298C polymorphism, there was no difference in distribution between the lung cancer and control groups. Gene interactions with smoking were significant for MTHFR C677T polymorphism. The MTHFR C677T CT and TT genotypes in association with smoking conferred a decreased risk of 0.706 (95% confidence interval=0.531-0.939) for lung cancer. CONCLUSION: Our results provide the first evidence that the C allele of MTHFR C677T may be associated with the development of lung cancer and may be a novel useful marker for primary prevention and anticancer intervention.