Lung cancer is the leading cause of cancer-related deaths worldwide. To identify genetic factors that modify the risk of lung cancer in individuals of Chinese ancestry, we performed a genome-wide association scan in 5,408 subjects (2,331 individuals with lung cancer (cases) and 3,077 controls) followed by a two-stage validation among 12,722 subjects (6,313 cases and 6,409 controls). The combined analyses identified six well-replicated SNPs with independent effects and significant lung cancer associations (P < 5.0 × 10(-8)) located in TP63 (rs4488809 at 3q28, P = 7.2 × 10(-26)), TERT-CLPTM1L (rs465498 and rs2736100 at 5p15.33, P = 1.2 × 10(-20) and P = 1.0 × 10(-27), respectively), MIPEP-TNFRSF19 (rs753955 at 13q12.12, P = 1.5 × 10(-12)) and MTMR3-HORMAD2-LIF (rs17728461 and rs36600 at 22q12.2, P = 1.1 × 10(-11) and P = 6.2 × 10(-13), respectively). Two of these loci (13q12.12 and 22q12.2) were newly identified in the Chinese population. These results suggest that genetic variants in 3q28, 5p15.33, 13q12.12 and 22q12.2 may contribute to the susceptibility of lung cancer in Han Chinese.

Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia is a ravaging condition of progressive lung scarring and destruction. Anti-inflammatory therapies including corticosteroids have limited efficacy in this ultimately fatal disorder. An important unmet need is to identify new agents that interact with key molecular pathways involved in the pathogenesis of pulmonary fibrosis to prevent progression or reverse fibrosis in these patients. Because aberrant activation of the Wnt/β-catenin signaling cascade occurs in lungs of patients with IPF, we have targeted this pathway for intervention in pulmonary fibrosis using ICG-001, a small molecule that specifically inhibits T-cell factor/β-catenin transcription in a cyclic AMP response-element binding protein binding protein (CBP)-dependent fashion. ICG-001 selectively blocks the β-catenin/CBP interaction without interfering with the β-catenin/p300 interaction. We report here that ICG-001 (5 mg/kg per day) significantly inhibits β-catenin signaling and attenuates bleomycin-induced lung fibrosis in mice, while concurrently preserving the epithelium. Administration of ICG-001 concurrent with bleomycin prevents fibrosis, and late administration is able to reverse established fibrosis and significantly improve survival. Because no effective treatment for IPF exists, selective inhibition of Wnt/β-catenin-dependent transcription suggests a potential unique therapeutic approach for pulmonary fibrosis.

To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan, and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10-6) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10-18), 6q22.2 (rs9387478, P = 4.14 × 10-10) and 6p21.32 (rs2395185, P = 9.51 × 10-9). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.

There has been conflicting evidence concerning the possible association between tuberculosis (TB) and subsequent risk of lung cancer. To investigate whether currently published epidemiological studies can clarify this association, we performed a systematic review of 37 case-control and 4 cohort studies (published between January 1966 and January 2009) and a meta-analysis of risk estimates, with particular attention to the role of smoking, passive smoking and the timing of diagnosis of TB on this relationship. Data for the review show a significantly increased lung cancer risk associated with preexisting TB. Importantly, the association was not due to confounding by the effects of tobacco use (RR 5 1.8, 95% confidence interval (CI) 5 1.4-2.2, among never smoking individuals), lifetime environmental tobacco smoke exposure (RR 5 2.9, 95%CI 5 1.6-5.3, after controlling) or the timing of diagnosis of TB (the increased lung cancer risk remained 2-fold elevated for more than 20 years after TB diagnosis). Interestingly, the association was significant with adenocarcinoma (RR 5 1.6, 95%CI 5 1.2-2.1), but no significant associations with squamous and small cell type of lung cancer were observed. Although no causal mechanism has been demonstrated for such an association, present study supports a direct relation between TB and lung cancer, especially adenocarcinomas. ' UICCKey words: systematic review; tuberculosis; meta-analysis; lung cancer Lung cancer as the most common cancer in the world represents a major public health problem. Worldwide it accounts for approximately 1.2 million cancer-related deaths each year.1 In men it is the largest cause of mortality, and in women it is the third largest cause, just after breast and intestinal cancer, but before cervical cancer.2-4 Good prevention and early detection of breast and cervical cancer mean that lung cancer will be the leading cause of mortality in women worldwide, too.5 Tuberculosis (TB) is another major cause of morbidity and mortality, especially in developing countries. Worldwide, approximately one third of people are infected with Mycobacterium tuberculosis, the causative microorganism, and with aging or weakening of the immune system, this infection can reactivate, leading to severe and prolonged pneumonia, pulmonary scarring and wasting.6 It has been well documented that lung inflammation and fibrosis from TB could induce genetic damage, which may increase the risk of lung cancer. [7][8][9] Along these lines, a number of retrospective case-control/prospective cohort studies have reported that subjects with a history of preexisting TB experience excess risk of lung cancer. However, the evidence has been inconsistent, and there has also been uncertainty about the temporal relationship between previous TB and lung cancer and possible residual confounding by cigarette smoking, passive smoking and the timing of diagnosis of TB. The determination of whether or not there is such an association has potential importance for managing TB, for screening of lung cancer an...