David C. Christiani

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BACKGROUND Most patients with non-small-cell lung cancer have no response to the tyrosine kinase inhibitor gefitinib, which targets the epidermal growth factor receptor (EGFR). However, about 10 percent of patients have a rapid and often dramatic clinical response. The molecular mechanisms underlying sensitivity to gefitinib are unknown. METHODS We(More)
We propose in this paper a unified approach for testing the association between rare variants and phenotypes in sequencing association studies. This approach maximizes power by adaptively using the data to optimally combine the burden test and the nonburden sequence kernel association test (SKAT). Burden tests are more powerful when most variants in a(More)
Germline mutation in serine/threonine kinase 11 (STK11, also called LKB1) results in Peutz-Jeghers syndrome, characterized by intestinal hamartomas and increased incidence of epithelial cancers. Although uncommon in most sporadic cancers, inactivating somatic mutations of LKB1 have been reported in primary human lung adenocarcinomas and derivative cell(More)
Lung cancer is the leading cause of cancer deaths worldwide, yet few genetic markers of lung cancer risk useful for screening exist. The let-7 family-of-microRNAs (miRNA) are global genetic regulators important in controlling lung cancer oncogene expression by binding to the 3' untranslated regions of their target mRNAs. The purpose of this study was to(More)
In humans the glutathione S-transferase (GST) genes encode four classes of proteins (GST) important in the detoxification of reactive electrophiles. Recently, a gene deletion polymorphism was discovered within the GST class theta locus that leads to a functional deficiency in GST theta activity within circulating red blood cells. In this study we have(More)
Environmental factors contributing to reduced birth weight are of great concern because of the well-known relation of birth weight to infant mortality and adverse effects in later life. We examined the associations between air pollution exposures during pregnancy and low birth weight among all full-term births (gestational age 37-44 weeks) for a 2-year(More)
OBJECTIVE Clinical predictors for acute respiratory distress syndrome (ARDS) have been studied in few prospective studies. Although transfusions are common in the intensive care unit, the role of submassive transfusion in non-trauma-related ARDS has not been studied. We describe here the clinical predictors of ARDS risk and mortality including the role of(More)
BACKGROUND Airborne particulate matter has been linked to excess morbidity and mortality. Recent attention has focused on the effects of particulate exposure on cardiac autonomic control. Inhaled particulates may affect the autonomic nervous system either directly, by eliciting a sympathetic stress response, or indirectly, through inflammatory cytokines(More)
Polymorphisms in several DNA repair genes have recently been identified, but little is known about their phenotypic significance. To determine whether variation in DNA repair genes is related to host DNA damage, we studied the association between polymorphisms in XRCC1 (codon 399) and ERCC2 (codon 751) and two markers of DNA damage, sister chromatid(More)
BACKGROUND There is scientific and public concern about commonly used chemicals, including phthalates, that are associated with reproductive toxicity in laboratory animals and are hormonally active. People are exposed to phthalates through diet, consumer products and medical devices. The present study explored whether environmental levels of phthalates are(More)