Biomedical subjects

John C Wain

Publications and source records attributed to John C Wain.

At least 19 recordsLinked to original sources

PubMed2005

Genotypes and haplotypes of matrix metalloproteinase 1, 3 and 12 genes and the risk of lung cancer.

The MMPs (matrix metalloproteinases) are a family of secreted zinc metalloproteases that degrade the collagens of the extracellular matrix important in tissue remodeling and repair during development and inflammation. We investigated the associations between polymorphisms of MMP-1 (-1607 1G/2G, rs1799750), MMP-3 (-1171 5A/6A, rs3025058), and MMP-12 (-82AG, rs2276109, and 1082A/G, rs652438) and the risk of lung cancer in 2014 Caucasian lung cancer patients and 1323 healthy controls. The results were analyzed using logistic regression models, adjusting for covariates. The four polymorphisms were in Hardy-Weinberg disequilibrium. Except for the 1G-1082A, the other linkage disequilibrium tests between the four MMP polymorphisms were statistically significant (P < 0.001). There was no overall association between individual MMP polymorphism and the risk of lung cancer. The MMP polymorphisms jointly were associated with a non-statistically significant higher risk of lung cancer, with the adjusted odds ratio (AOR) of subjects with 5+ variant alleles versus zero variant allele of 1.31 [95% confidence interval (CI), 0.92-1.88]. Stronger associations were observed in never-smokers and males, with the corresponding AORs of 2.44 (95%CI, 1.10-5.43, P(trend) = 0.04) in never smokers and 1.35 (95%CI, 0.79-2.30, P(trend) = 0.04) in men. In haplotype analysis, the 1G-6A-82A-1082G haplotype was associated with higher risk of lung cancer among never smokers, with the AOR of 3.65 (95%CI, 1.62-8.20) when compared with the most common 1G-5A-82A-1082A haplotype. In conclusion, the combined MMP genotypes and associated haplotypes may be associated with higher risk of lung cancer, particularly among never smokers and men.

Adult↗

PubMed2005

Predictors of recurrence in thymic tumors: importance of invasion, World Health Organization histology, and size.

OBJECTIVE: This study sought to define predictors of recurrence after resection of thymic tumors. METHODS: A single-institution retrospective study was performed of 179 patients who underwent resection of a thymic tumor from 1972 through 2003. RESULTS: Resection was complete in 90% (161/179) of patients. After a median follow-up of 115 months, the recurrence rate was 11% (20/179), the tumor-related death rate was 7.8% (14/179), and the overall death rate was 36.3% (65/179). Tumor recurrence correlated with advanced stage and histology (P < .0001). The difference in recurrence between Masaoka stage I (0) and II (1.7% [1/59]) was insignificant. Recurrence rates correlated with World Health Organization tumor type: A and AB, 0%; B1 and B2, 8% (4/51); B3, 27% (14/51); and C, 50% (2/4; P < .0001). Tumor size separation into quintiles demonstrated a step-up of recurrence at 8 cm (<8 cm, 1.8% [2/113]; > or =8 cm, 28% [18/64]; P < .003). Multivariate Cox modeling demonstrated that Masaoka stage (odds ratio, 5.70; P < .001), World Health Organization histology (odds ratio, 5.77; P = .003), and size (odds ratio, 1.16; P = .001) were independent predictors of recurrence. CONCLUSION: The Masaoka staging system could be collapsed to 3 degrees of invasion by combining stages I and II. The World Health Organization histologic type can be simplified for clinical use into A (A, AB), early B (B1, B2), advanced B (B3), and C tumors. Size of 8 cm or larger is an independent risk factor, even when patients with Masaoka stage III tumors are considered alone, and might identify candidates for preoperative therapy.

Adult↗

PubMed2005

BLT1-mediated T cell trafficking is critical for rejection and obliterative bronchiolitis after lung transplantation.

Leukotriene B4 is a lipid mediator that recently has been shown to have potent chemotactic activity for effector T lymphocytes mediated through its receptor, BLT1. Here, we developed a novel murine model of acute lung rejection to demonstrate that BLT1 controls effector CD8+ T cell trafficking into the lung and that disruption of BLT1 signaling in CD8+ T cells reduces lung inflammation and mortality in the model. In addition, we used BLT1-deficient mice and a BLT1 antagonist in two tracheal transplant models of lung transplantation to demonstrate the importance of BLT1 for the recruitment of T cells into tracheal allografts. We also show that BLT1-mediated CD8+ T cell recruitment plays an important role in the development of airway fibroproliferation and obliteration. Finally, in human studies of lung transplant recipients, we found that BLT1 is up-regulated on T lymphocytes isolated from the airways of patients with obliterative bronchiolitis. These data demonstrate that BLT1 contributes to the development of lung rejection and obliterative bronchiolitis by mediating effector T lymphocyte trafficking into the lung. This is the first report that describes a pathologic role for BLT1-mediated T lymphocyte recruitment in disease and identifies BLT1 as a potential therapeutic target after lung transplantation.

Animals↗

PubMed2005

Polyphenol associated-DNA adducts in lung and blood mononuclear cells from lung cancer patients.

The formation of smoking induced-DNA adducts is a critical factor in the induction of human lung cancer. As derivates of benzene and polyaromatic hydrocarbons (PAHs) are important compounds of tobacco smoke, in DNA isolated from human lung and blood mononuclear cells (MNCs) from 38 lung cancer patients, we used the (32)P-postlabeling assay to detect polyphenol associated DNA adducts. Two DNA adducts were detected in blood MNCs and lung tissue that co-chromatographed with DNA modifications from HL60 cells treated with combinations of benzene metabolites (e.g., hydroquinone and benzenetriol). These adducts were designated polyphenol-associated DNA adducts. Relative adduct levels for polyphenolic adducts were five-fold higher than aromatic adducts in both lung and MNCs. A significant correlation was observed between levels of polyphenol adducts and total duration of cigarette smoking in lung (r=0.34; P<0.04) and MNCs (r=0.7; P<0.04), but no correlation between levels of polyphenol adducts and pack-years consumption of cigarettes nor time since quitting smoking in former smokers. Long term former smokers and the one non-smoker in the study had detectable levels of polyphenol adducts. Surprisingly, the levels of polyphenol adducts in MNCs were highly correlated with aromatic adduct levels (r=0.84; P<0.001). Individual aromatic adducts in MNCs also correlated with polyphenol adducts. Total polyphenol adduct levels had a correlation with aromatic DNA adduct levels in lung tissue (r=0.46; P<0.01). To our knowledge these results are the only comparison of adducts in MNCs with lung tissue, and the only data set indicating that blood MNCs are a valid surrogate for lung adduct DNA burden.

Adenocarcinoma↗

PubMed2005

Polymorphisms in ERCC1 and grade 3 or 4 toxicity in non-small cell lung cancer patients.

PURPOSE: ERCC1 is a lead enzyme in the nucleotide excision repair pathway of DNA repair. Polymorphisms have been identified in the ERCC1 gene, the C8092A and codon 118 polymorphisms, which may lead to an altered capacity to regenerate damaged normal tissue and greater treatment-related toxicity. EXPERIMENTAL DESIGN: Using logistic regression models, we evaluated the ERCC1 C8092A and codon 118 polymorphisms and their association with the occurrence of grade 3 or 4 toxicity in 214 stage III and IV non-small cell lung cancer patients treated first line with platinum-based chemotherapy. Adjusting covariates were performance status and type of treatment regimen. RESULTS: There was no statistically significant association between either the C8092A or codon 118 polymorphism and overall or hematologic grade 3 or 4 toxicity. However, carrying at least one variant ERCC1 C8092A allele was associated with a significantly increased risk of grade 3 or 4 gastrointestinal toxicity (adjusted odds ratio, 2.33; 95% confidence interval, 1.07-5.05; P = 0.03). CONCLUSIONS: Adjusting for performance status and type of treatment regimen, carrying at least one ERCC1 8092A allele is associated with a >2-fold increase in grade 3 or 4 gastrointestinal toxicity among platinum-treated non-small cell lung cancer patients.

Adult↗

PubMed2005

Esophageal leiomyoma: a 40-year experience.

BACKGROUND: Esophageal leiomyomas, although infrequent, are the most common benign intramural tumors of the esophagus. They represent 10% of all gastrointestinal leiomyomas and frequently cause symptoms, necessitating resection. METHODS: The Massachusetts General Hospital Pathologic Database was reviewed over a 40-year period for patients who underwent surgical resection of esophageal leiomyomas. Data analyzed included demographic information, presenting symptoms, tumor location, tumor characteristics and histology, diagnostic procedures, and treatment modalities/outcomes. Fifty-three patients were identified; 31 patients were symptomatic from their leiomyomas. RESULTS: Symptomatic patients presented at a mean age of 44 years old and exhibited a twofold male predominance. Mean tumor diameter among symptomatic patients was 5.3 cm, as compared to 1.5 cm in asymptomatic patients (p < 0.0001). Thirty of the symptomatic patients had solitary leiomyomas, and 1 patient had five separate leiomyomas. Eighty-four percent of the lesions in symptomatic patients occurred in the lower two-thirds of the esophagus, with epigastric discomfort being the most common presenting symptom. Among patients operated on solely for leiomyoma, 97% were enucleated without an esophageal resection. None of the leiomyomas showed malignant transformation or recurrence. All symptomatic patients had relief of symptoms, with no perioperative morbidity or mortality. CONCLUSIONS: In a large pathologic series, over half of all patients with esophageal leiomyomas were symptomatic. Larger tumors were significantly more likely to be symptomatic. Local enucleation by a variety of surgical approaches was accomplished in most patients. All symptomatic patients had relief of symptoms, with no perioperative morbidity or mortality. There was no observed tendency for malignant transformation or recurrence.

Adult↗

PubMed2005

Surgical treatment of esophageal high-grade dysplasia.

BACKGROUND: Barrett's esophagus, high-grade dysplasia (HGD), and invasive cancer are steps in the progression of esophageal adenocarcinoma. While surgery is recommended for resectable invasive adenocarcinoma, a number of treatment modalities are advocated for HGD. The purpose of this study is to determine the outcomes after surgery for HGD. METHODS: We identified cases of HGD based on endoscopic biopsy in a single institution's databases from 1980 through 2001. Records were reviewed for patient characteristics, treatments, staging, and outcomes. RESULTS: In a 22-year period, 869 cases of esophageal adenocarcinoma and 1,614 cases of Barrett's esophagus were diagnosed. Of these, 115 had HGD without pretreatment evidence of invasion. Forty-nine patients with HGD underwent resection (mean age, 59 years) as initial treatment. Forty-seven had endoscopic treatment (mean age, 70 years) by photodynamic therapy or endoscopic mucosal resection. Seven of the endoscopically treated patients failed, with three undergoing surgery and four observation. Nineteen patients were initially observed, with six eventually having surgery. For the 49 initially treated surgically, one (2%) operative mortality occurred. Invasive adenocarcinoma was present in 18 (37%). The five-year survival was 83% for all resected HGD patients (91% for those without invasion, 68% with invasion). Three of the eight deaths in those with invasion were from recurrent adenocarcinoma. CONCLUSIONS: Surgical resection of esophageal HGD can be performed with low mortality and allows long-term survival. A significant percentage with an initial diagnosis of HGD will have invasive disease at resection. Surgery is the optimal treatment for HGD unless contraindicated by severe comorbidities.

Adenocarcinoma↗

PubMed2005

Adjuvant radiation of stage III thymoma: is it necessary?

BACKGROUND: The criteria for administration of adjuvant radiation therapy after thymoma resection remains controversial, and it is unclear whether patients with Masaoka stage III thymoma benefit from adjuvant radiation. The goal of this report was to determine whether or not this group benefits from radiation therapy in disease-specific survival and disease-free survival. METHODS: Case records of the Massachusetts General Hospital were retrospectively reviewed from 1972 to 2004. One hundred and seventy-nine patients underwent resection for thymoma, of which 45 had stage III disease. RESULTS: Forty-five stage III patients underwent resection and in 36 it was complete. Thirty-eight stage III patients received radiation therapy. Baseline prognostic factors between radiated and nonradiated groups were similar. The addition of adjuvant radiotherapy did not alter local or distant recurrence rates in patients with stage III thymoma. Disease-specific survival at 10 years in stage III patients who did not receive radiation was 75% (95% confidence interval, 32% to 100%) and in patients who did receive radiation therapy it was 79% (95% confidence interval, 64% to 94%) (p = 0.21). The most common site of relapse was the pleura. CONCLUSIONS: Most patients who have stage III thymoma undergo complete resection. Some patients enjoy prolonged disease-free survival without adjuvant radiation after resection of stage III thymoma. Radiation does not seem to prevent pleural recurrences when given after resection of stage III thymomas. The use of routine adjuvant radiation after a complete resection of stage III thymoma needs to be re-addressed. There may be a role for the use of chemotherapy to reduce pleural recurrences.

Adolescent↗

PubMed2005

Tracheoplasty for expiratory collapse of central airways.

BACKGROUND: Severe central airway obstruction due to expiratory collapse occurs with malacia of intrathoracic trachea and main bronchi, often with chronic obstructive pulmonary disease. Bronchoscopically observed, it is confirmed by inspiratory-expiratory computerized tomographic chest scans. Prior attempts at surgical stabilization have not given dependable results. METHODS: Posterior tracheobronchial splinting with polypropylene mesh (Marlex) holds cartilages in more normal configuration, and fixes redundant membranous walls. Fourteen consecutive patients were so treated for severe dyspnea. Prior trials of various autologous and exogenous splints failed. RESULTS: All felt subjectively improved early, with decreased dyspnea, cough, and secretion retention, and with increased activities. Mean forced expiratory volume in 1 second rose from 51% predicted to 73% (p = 0.009), and peak expiratory flow rate from 49% to 70% (p < 0.00001). One patient was lost to follow-up (1 year), 1 died of unrelated cause (5 years), 1 died of chronic obstructive pulmonary disease (3 years), and 1 had decreased respiratory function over 5 years. Ten patients were available for long-term follow-up: 6 were judged to have an excellent result, 2 were good, and 2 were poor due to collapse of unsplinted main bronchi. CONCLUSIONS: Complete splinting of all malacic central airways with Marlex restores anatomic configuration and permanently prevents expiratory collapse, with relief of extreme dyspnea, cough, and secretion retention.

Adult↗

PubMed2005

Tracheal compression caused by straight back syndrome, chest wall deformity, and anterior spinal displacement: techniques for relief.

BACKGROUND: Straight back syndrome and other causes of extreme narrowing of the space between sternal notch and vertebrae can cause critical tracheal obstruction. Additional points of compression may result from the brachiocephalic artery and from anterior vertebral displacement. METHODS: Individualized surgical maneuvers are necessary to correct all points of obstruction. Techniques include sternoplasty, sternal division, reimplantation of brachiocephalic artery, correction of severe pectus excavatum, and posterior wall tracheoplasty. RESULTS: Four patients were successfully treated by individualized techniques with complete long-term relief of critical tracheal obstruction. CONCLUSIONS: Severe tracheal compression caused by straight back syndrome and other causes of narrowed sternospinal channel is surgically correctable.

Adult↗

PubMed2005

Laryngotracheoplastic resection for primary tumors of the proximal airway.

BACKGROUND: Primary tumors of the airway with proximity to vocal cords and recurrent laryngeal nerves can be resected with sparing of the larynx. Long-term data on survival and local recurrence after laryngotracheal resection are scarce. METHODS: We conducted a retrospective study of laryngotracheal resection and reconstruction for primary tumors of the airway since 1972. RESULTS: Twenty-five patients aged 15 to 77 years presented with adenoid cystic carcinomas (n = 9), squamous cell carcinomas (n = 6), and other airway tumors (n = 10). Subglottic resection consisted of anterior cricoid in 5 patients; posterior cricoid mucosa in 9 patients, with resection of the posterior cricoid plate in 3 patients; lateral resection in 7 patients; and combined anterior and posterior elements in 4 patients. Vascularized trachea was tailored to reconstruct the defect. Seven patients without hoarseness required resection of the recurrent laryngeal nerve, and 4 other patients with hoarseness did not. There were no operative deaths. Two (8.0%) patients who had received prior high-dose cervical radiation had anastomotic separation, one requiring laryngectomy. One patient needed permanent tracheostomy, and temporary (<2 months) airway tubes were used in 5 patients. Sixteen patients received postoperative radiation. Median follow-up was 101 months. Four (16%) patients died of disease. Overall survival at 5 and 10 years was 79% and 64%, respectively. No patient underwent laryngectomy for recurrence. CONCLUSION: Laryngotracheal resection and immediate reconstruction for subglottic tumors is achieved with good preservation of voice, low morbidity, and no compromise of long-term survival.

Adolescent↗

PubMed2005

Dietary iron, zinc, and calcium and the risk of lung cancer.

BACKGROUND: Iron, zinc, and calcium are all involved in the metabolism of reactive oxygen species and may compete with each other for similar binding sites. Dietary intakes of these micronutrients have been associated with altered risks of colorectal, breast, and prostate cancers. METHODS: In this Massachusetts hospital-based case-control study of 923 patients with lung cancer and 1125 healthy controls, we studied the associations between dietary iron, zinc, and calcium intake and the risk of lung cancer. Dietary intake was assessed at the time of recruitment (1992 to 2000) with the use of a 126-item semiquantitative food-frequency questionnaire. We analyzed the data using multiple logistic regression models adjusting for smoking history and other potential risk factors. RESULTS: The adjusted odds ratios of dietary iron, zinc, and calcium from food sources were 1.45 (95% confidence interval=1.03-2.06), 0.71 (0.50-0.99), and 1.64 (1.17-2.29), respectively, for the highest quintile versus the lowest quintile of each micronutrient. Stronger associations between micronutrients and lung cancer risk were found when iron, zinc, and calcium were included together in the same model. The associations between dietary micronutrients intake and lung cancer risk were stronger among current smokers than among former smokers. When we examined intake from supplements as well as diet, associations were similar to those for diet alone. CONCLUSIONS: Dietary iron, zinc, and calcium may play an important role in the development of lung cancer, especially among current smokers. These results need to be confirmed in large prospective studies.

Adult↗

PubMed2005

Indirect recognition of MHC class I allopeptides accelerates lung allograft rejection in miniature swine.

The role of indirect allorecognition in graft rejection is examined in two experiments using a swine lung transplantation model. First, two swine received class I mismatched grafts without immunosuppression; another two recipients were treated postoperatively with cyclosporine (CsA). These swine exhibited acute and chronic rejection, respectively. All four recipients developed T-cell reactivity to donor-derived class I major histocompatibility complex (MHC) peptides. Second, six swine were immunized with synthetic donor-derived class I allopeptides prior to transplantation. Control groups consisted of nonimmunized recipients (n = 6) and recipients immunized with an irrelevant peptide (n = 3). These recipients all received a 12-day course of post-operative CsA. Swine immunized with allopeptides exhibited accelerated graft rejection, as compared to both control groups (p < 0.01 and p = 0.03, respectively). Within the experimental group, the dominant histologic finding was acute rejection (AR). Obliterative bronchiolitis (OB) was seen in the graft with the longest survival. Both control groups showed a lesser degree of AR, with four out of six nonimmunized swine ultimately developing OB. These studies suggest that indirect allorecognition is operative during lung allograft rejection, and that pre-transplant sensitization to donor-derived MHC allopeptides can accelerate graft rejection.

Acute Disease↗

PubMed2005

Matrix metalloproteinase-1 promoter polymorphism and lung cancer risk.

Extracellular matrix-degrading matrix metalloproteinase-1 (MMP-1) is an interstitial collagenase that degrades the interstitial types I, II, and III collagens, and overexpression of MMP-1 is associated with cancer development and cellular invasion. The 2G allele of the MMP-1 -1607 1G/2G polymorphism is associated with enhanced transcriptional activity. We investigated the association between the MMP-1 1G/2G polymorphism and lung cancer risk in 1,752 Caucasian lung cancer patients and 1,363 healthy controls. There were no overall associations between the MMP-1 genotypes and risk of lung cancer, with the adjusted odds ratios of 1.15 [95% confidence interval (CI), 0.94-1.40] for the 1G/2G genotype and 1.14 (95% CI, 0.90-1.45) for the 2G/2G genotype, when versus the 1G/1G genotype. Stratified analyses suggested higher lung cancer risk for the 2G allele in never-smokers and males, with the adjusted odds ratios of 1.67 (95% CI, 1.02-2.76; 1G/2G) and 1.50 (95% CI, 0.86-2.62; 2G/2G) in never-smokers; and 1.30 (95% CI, 1.00-1.75; 1G/2G) and 1.23 (95% CI, 0.88-1.73; 2G/2G) in males, respectively. In conclusion, genotypes containing the 2G allele of the MMP-1 polymorphism are associated with higher risk of lung cancer in never-smokers and in males.

Adult↗

PubMed2005

Gene-smoking interaction associations for the ERCC1 polymorphisms in the risk of lung cancer.

Cigarette smoking may induce DNA damage. Lower DNA repair capacities have been associated with higher risk of lung cancer. Excision repair cross-complementing group 1 (ERCC1) is the lead enzyme in the nucleotide excision repair process, and low expression of ERCC1 mRNA levels has been associated with higher risk of cancers. We examined the association between two polymorphisms of ERCC1, 8092C > A (rs3212986) and 19007T > C (codon 118, rs11615), which are associated with altered ERCC1 mRNA stability and mRNA levels, in 1,752 Caucasian lung cancer patients and 1,358 controls. The results were analyzed using logistic regression models, adjusting for relevant covariates. The two polymorphisms were in Hardy-Weinberg disequilibrium and in linkage disequilibrium. There was no overall association between ERCC1 polymorphisms and lung cancer risk, with the adjusted odds ratios (AOR) of 1.26 [95% confidence interval (95% CI), 0.81-1.96] for the 8092C > A polymorphism (A/A versus C/C) and 0.93 (95% CI, 0.67-1.30) for the 19007T > C polymorphism (C/C versus T/T). Stratified analyses revealed that the AORs for the 8092C > A polymorphism (A/A versus C/C) decreased significantly as pack-years increased, with the AOR of 2.11 (95% CI, 1.03-4.31) in never smokers and 0.50 (95% CI, 0.25-1.01) in heavy smokers (>/=56 pack-years), respectively. Consistent results were found when gene-smoking interaction was incorporated by joint effects and interactions models that considered both discrete and continuous variables for cumulative smoking exposure. The same direction for the gene-smoking interaction was found for the 19007T > C polymorphism, although the interaction was not statistically significant. In conclusion, ERCC1 8092C > A polymorphism may modify the associations between cumulative cigarette smoking and lung cancer risk.

Adult↗

PubMed2005

Vitamin D is associated with improved survival in early-stage non-small cell lung cancer patients.

Vitamin D may inhibit the development and progression of a wide spectrum of cancers. We investigated the associations of surgery season and vitamin D intake with recurrence-free survival (RFS) and overall survival in 456 early-stage non-small cell lung cancer patients. The data were analyzed using log-rank test and Cox proportional hazards models. The median (range) follow-up time was 71 (0.1-140) months, with 161 recurrence and 231 deaths. Patients who had surgery in summer had a better RFS than those who had surgery in winter (adjusted hazard ratio, 0.75; 95% confidence interval, 0.56-1.01), with 5-year RFS rates of 53% (45-61%) and 40% (32-49%), respectively (P = 0.10, log-rank test). Similar association between surgery season and RFS was found among the 321 patients with dietary information (P = 0.33, log-rank test). There was no statistically significant association between vitamin D intake and RFS. Because both season and vitamin D intake are important predictors for vitamin D levels, we investigated the joint effects of surgery season and vitamin D intake. Patients who had surgery during summer with the highest vitamin D intake had better RFS (adjusted hazard ratio, 0.33; 95% confidence interval, 0.15-0.74) than patients who had surgery during winter with the lowest vitamin D intake, with the 5-year RFS rates of 56% (34-78%) and 23% (4-42%), respectively. Similar associations of surgery season and vitamin D intake with overall survival were also observed. In conclusion, the joint effects of surgery season and recent vitamin D intake seem to be associated with the survival of early-stage non-small cell lung cancer patients.

Adult↗

PubMed2005

Lung transplantation biopsy specimens with bronchiolitis obliterans or bronchiolitis obliterans organizing pneumonia due to aspiration.

CONTEXT: Bronchiolitis obliterans (BO) is generally thought to be a marker of chronic airway rejection in patients who have undergone lung transplantation. Bronchoscopic biopsy specimens, by virtue of their small size, may sample only BO and not a lesion of bronchiolitis obliterans organizing pneumonia (BOOP). A role for ongoing chronic infection or aspiration has also been suggested, and the distinction of these etiologies may be difficult clinically and pathologically. OBJECTIVE: To investigate the etiology of BO and BOOP in lung transplantation patients who had chronic aspiration. DESIGN: This is a clinicopathologic study of 7 patients who had undergone lung transplantation in which biopsy findings suggested the possibility of chronic airway rejection but in which aspiration was subsequently proven as a cause of the bronchiolar disease. RESULTS: All patients were men, who ranged in age from 19 to 57 years. A clinical diagnosis of aspiration was considered based on history, acid reflux testing, and radiographic findings in all 7 patients. Three patients had BO and 4 patients had BOOP. Histiocytic giant cells or foreign material was absent. The interval from transplantation to BO ascribed to aspiration ranged from 2.5 months to 7 years. The patients were treated aggressively with medication for gastroesophageal reflux disease. Their respiratory function and chest radiography results improved. CONCLUSION: Although BO may be a manifestation of rejection, it may also be a manifestation of aspiration. Because the latter is potentially correctable, aspiration should be considered etiologically in lung transplantation patients with either BO or BOOP. Reliable distinction between aspiration-related or rejection-related BO and BOOP cannot be made on morphologic grounds alone. Clinical and radiologic correlations are indicated to establish the distinction.

Adult↗

PubMed2004

The SOD2 Val/Val genotype enhances the risk of nonsmall cell lung carcinoma by p53 and XRCC1 polymorphisms.

BACKGROUND: Exogenous reactive oxygen species (ROS) induces DNA damage. Manganese superoxide dismutase (SOD2) catalyzes the dismutation of superoxide radicals, a major type of ROS, into hydrogen peroxide. p53 is a tumor suppressor gene, and X-ray cross-complementing group 1 (XRCC1) is involved in the base-excision repair of ROS-induced DNA damage. METHODS: The authors investigated whether the SOD2 Ala16Val polymorphism modifies the associations between p53 Arg72Pro and XRCC1 Arg399Gln polymorphisms and the risk of nonsmall cell lung carcinoma (NSCLC) in a case-control study of 935 Caucasian patients with NSCLC and 1233 healthy control participants. The results were analyzed using logistic regression models that were adjusted for possible confounding variables. RESULTS: There was no association between p53 or XRCC1 polymorphism and NSCLC risk for individuals with SOD2 Ala/Ala or Ala/Val genotype. For individuals with the SOD2 Val/Val genotype, greater risks were found in association with p53 (variant Pro allele vs. Arg/Arg), XRCC1 (variant Gln allele vs. Arg/Arg), and the combination of the two polymorphisms ("double variant" vs. "double wild type"), with the adjusted odds ratios (ORs) of 1.84 (95% confidence interval [95% CI], 1.20-2.82), 1.39 (95% CI, 0.98-2.21), and 2.54 (95% CI, 1.38-4.68), respectively. Furthermore, the greater risk for the double variant of p53 and XRCC1 in the SOD2 Val/Val genotype group was specific only for patients with adenocarcinoma and not for patients with squamous cell carcinoma, with adjusted ORs of 3.31 (95% CI, 1.68-6.51) and 0.69 (95% CI, 0.24-2.02), respectively. CONCLUSIONS: The SOD2 Val/Val genotype may increase the risk of NSCLC carried by XRCC1 and p53 polymorphisms, particularly for adenocarcinoma.

Adult↗