Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection.

Background: Although cigarette smoking is the major risk factor for lung cancer, only 7% of female lung cancer patients in Taiwan have a history of smoking. The genetic mechanisms of carcinogenesis in nonsmokers are unclear, but semaphorins have been suggested to play a role as lung tumor suppressors. This report is a comprehensive analysis of the molecular signature of nonsmoking female lung cancer patients in Taiwan, with a particular focus on the semaphorin gene family.Methods: Sixty pairs of tumor and adjacent normal lung tissue specimens were analyzed by using Affymetrix U133plus2.0 expression arrays. Differentially expressed genes in tumor tissues were identified by a paired t test and validated by reverse transcriptase-PCR and immunohistochemistry. Functional analysis was conducted by using Ingenuity Pathway Analysis as well as gene set enrichment analysis and sigPathway algorithms. Kaplan-Meier survival analyses were used to evaluate the association of SEMA5A expression and clinical outcome.Results: We identified 687 differentially expressed genes in non-small cell lung carcinoma (NSCLC). Many of these genes, most notably the semaphorin family, were participants in the axon guidance signaling pathway. The downregulation of SEMA5A in tumor tissue, both at the transcriptional and translational levels, was associated with poor survival among nonsmoking women with NSCLC.Conclusions: In summary, several semaphorin gene family members were identified as potential therapeutic targets, and SEMA5A may be useful as a prognostic biomarker for NSCLC, which may also be gender specific in Taiwanese patients.Impact: A novel biomarker for NSCLC is identified. Cancer Epidemiol Biomarkers Prev; 19(10); 2590-7. ©2010 AACR.

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A multicenter case-control study was conducted in northern and southern Taiwan to clarify the independent and combined effects of alcohol intake, tobacco smoking and betel quid chewing on the risk of esophageal cancer. A total of 513 patients with newly diagnosed and histopathologically confirmed squamous cell carcinoma of the esophagus and 818 gender, age and study hospitalmatched controls were included. We found a significant doseresponse relationship between the duration and intensity of consumption of the 3 substances and the development of this neoplasm in this site. Although the amount of alcohol consumed had a stronger effect on the risk of esophageal cancer than the number of years it was consumed, however, the number of years one smoked had a stronger effect on the risk than the amount of cigarettes consumed. The strongest risk factor of esophageal cancer was alcohol intake, with highest risk (OR ‫؍‬ 13.9) being for those who consumed more than 900 g/day-year. Combined exposure to any 2 of 3 substances brought the risks up to 8.8 -19.7 fold and, to all 3 substances, to 41.2-fold. A multiplicative interaction effect for alcohol drinkers who smoked on cancer risk was detected, whereas an additive interaction effect was found among drinkers who chewed. The combined effect of all 3 substances accounted for 83.7% of the attributable fraction of contracting esophageal cancer in this population. In conclusion, these results suggest that the intensity and the length of time alcohol and tobacco are used play different roles in the etiology of esophageal cancer. Alcohol separately interacts with tobacco and betel quid in a differently synergistic way in determining the development of this site of cancer.

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N-α-acetyltransferase 10 protein, Naa10p, is an N-acetyltransferase known to be involved in cell cycle control. We found that Naa10p was expressed lower in varieties of malignancies with lymph node metastasis compared with non-lymph node metastasis. Higher Naa10p expression correlates the survival of lung cancer patients. Naa10p significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration. Forced expression of PIX in Naa10-transfected tumor cells restored the migration and metastasis ability. We suggest that Naa10p functions as a tumor metastasis suppressor by disrupting the migratory complex, PIX-GIT- Paxillin, in cancer cells.

Performing cervical esophagogastric anastomoses using a circular mechanical stapler had a shorter operating time and a comparable outcome to the hand-sewn method. The circular mechanical stapler could be used as an alternative for cervical esophagogastric anastomosis after resection for esophageal squamous cell cancer.

Background. Preserving functional walking capacity and nutritional status is important for patients with esophageal cancer, but no effective intervention is available, particularly during active treatment.Methods. This pilot randomized controlled trial tested the effects of a walk-and-eat intervention for patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy. Participants with locally advanced esophageal cancer stage IIB or higher (n 5 59) were randomly assigned to receive the walk-and-eat intervention (n 5 30; nurse-supervised walking three times per week and weekly nutritional advice) or usual care (n 5 29; control group) during 4-5 weeks of chemoradiotherapy. Primary endpoints were changes in distance on the 6-minute walk test, hand-grip strength, lean muscle mass, and body weight between initiation and completion of intervention.