Aggregation of cancer among relatives of never-smoking lung cancer patients.
ABSTRACT The authors evaluated the familial aggregation of lung and other cancers in first-degree relatives of lung cancer patients self-reported to be lifetime never smokers. The data, derived from a large lung cancer case-control study, included 2,465 first-degree relatives of 316 never smoker lung cancer cases and 2,441 first-degree relatives of 318 never smoker controls, frequency matched to the cases on age, gender and ethnicity. The median age of the cases and the controls was 61 years, about 2/3 were women, and about 80% were Caucasian. Overall, there was a 25% excess risk [95% CI (1.05-1.50)] of any type of cancer among the first-degree relatives of cases, and case offspring exhibited a 2-fold excess cancer risk (1.03-4.10) compared with control offspring. There was also a 44% excess risk (1.05-1.97) of young onset cancers (before age 50) among relatives of cases. Smoking case relatives had an increased risk of any cancer [odds ratio (OR) = 1.36 (1.03-1.81)] and a 5.52-fold risk (1.19-25.51) of young onset lung cancer compared with smoking control relatives. Female case relatives had a 58% excess breast cancer risk (1.04-2.43), and case mothers a 2.57-fold breast cancer risk (1.16-4.24). A significant excess of testicular cancer was observed among case male relatives [OR = 12.32 (1.71-88.90)], although based on only 9 cases. The age at lung cancer diagnosis tended to be earlier in case relatives (61.4, SD = 12.9) compared with control relatives (66.2, SD = 11.4; p = 0.07). Our analysis provides further evidence for the importance of genetic factors for lung cancer in never smokers.
Article: Lung cancer in never smokers.[show abstract] [hide abstract]
ABSTRACT: Lung cancer in never smokers (LCINS) has lately been recognized as a unique disease based on rapidly gained knowledge from genomic changes to treatment responses. The focus of this article is on current knowledge and challenges with regard to LCINS expanded from recent reviews highlighting five areas: (1) distribution of LCINS by temporal trends, geographic regions, and populations; (2) three well-recognized environmental risk factors; (3) other plausible environmental risk factors; (4) prior chronic lung diseases and infectious diseases as risk factors; and (5) lifestyles as risk or protective factors. This article will also bring attention to recently published literature in two pioneering areas: (1) histological characteristics, clinical features with emerging new effective therapies, and social and psychological stigma; and (2) searching for susceptibility genes using integrated genomic approaches.Seminars in Respiratory and Critical Care Medicine 02/2011; 32(1):10-21. · 2.43 Impact Factor
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ABSTRACT: Squamous cell carcinoma (SCC) is an epithelial malignancy involving many anatomical sites and is the most common cancer capable of metastatic spread. Development of early diagnosis methods and novel therapeutics are important for prevention and mortality reduction. In this effort, numerous molecular alterations have been described in SCCs. SCCs share many phenotypic and molecular characteristics, but they have not been extensively compared. This article reviews SCC as a disease, including: epidemiology, pathology, risk factors, molecular characteristics, prognostic markers, targeted therapy, and a new approach to studying SCCs. Through this comparison, several themes are apparent. For example, HPV infection is a common risk factor among the four major SCCs (NMSC, HNSC, ESCC, and NSCLC) and molecular abnormalities in cell-cycle regulation and signal transduction predominate. These data reveal that the molecular insights, new markers, and drug targets discovered in individual SCCs may shed light on this type of cancer as a whole.American journal of cancer research. 01/2011; 1(3):275-300.
Article: miR-511 and miR-1297 Inhibit Human Lung Adenocarcinoma Cell Proliferation by Targeting Oncogene TRIB2.[show abstract] [hide abstract]
ABSTRACT: microRNAs (miRNAs) are small noncoding RNAs that regulate genes and contribute to many kinds of human diseases, including cancer. Two miRNAs, miR-511 and miR-1297, were investigated for a possible role in adenocarcinoma based on predicted binding sites for the TRIB2 oncogene by microRNA analysis software, and the pcDNA-GFP-TRIB2-3'UTR vector was constructed to investigate the interaction between TRIB2 and miR-511/1297 in the adenocarcinoma cell line A549. Green fluorescent protein (GFP) expression was estimated by fluorescence microscopy and flow cytometry after A549 cells were co-transfected with miR-511 (or miR-1297) and pcDNA-GFP-TRIB2-3'UTR vector. The expression of GFP in the miR-511- and miR-1297-treated cells was significantly downregulated in contrast with the negative-control (NC) miRNA-treated cells. The decreased expression of TRIB2 was further detected after miR-511 (or miR-1297) treatment by western blotting. The MTT test showed inhibition of A549 cell proliferation and Annexin V-FITC/PI dual staining showed increased apoptosis in the miR-511- and miR-1297-treated cells compared to the NC cultures. A transcription factor downstream of TRIB2, the CCAAT/enhancer-binding protein alpha (C/EBPα), was expression at higher levels after miR-511 (or miR-1297) decreasing TRIB2 expression. Our results illustrate that miR-511 and miR-1297 act as tumor suppressor genes, which could suppress A549 cell proliferation in vitro and in vivo by suppressing TRIB2 and further increasing C/EBPα expression.PLoS ONE 01/2012; 7(10):e46090. · 4.09 Impact Factor