A genetic sequence variant (GSV) at susceptibility loci of 5p15.33 (TERT-CLPTM1L) is associated with survival outcome in locally advanced and metastatic non-small-cell lung cancer (NSCLC).

INTRODUCTION: Lung cancer is a leading cause of cancer-related mortality in North America. In addition to tobacco smoking, inherited genetic factors can also influence the development of lung cancer. These genetic factors may lead to biologically distinct subsets of cancers that have different outcomes. We evaluated whether genetic sequence variants (GSVs) associated with lung cancer risk are associated with overall survival (OS) and progression-free survival (PFS) in stage-III-IV non-small-cell lung cancer (NSCLC) patients. METHODS: A total of 20 candidate GSVs in 12 genes previously reported to be associated with lung cancer risk were genotyped in 564 patients with stage-III or IV NSCLC. Multivariate Cox proportional hazard models adjusted for potential clinical prognostic factors were generated for OS and PFS. RESULTS: After taking into account multiple comparisons, one GSV remained significant: rs4975616 on chromosome 5p15.33, located near the TERT-CLPTM1L gene. The adjusted hazard ratio (aHR) for OS was 0.75 (0.69-0.91), p = 0.002; for PFS aHR was 0.74 (0.62-0.89), p < 0.001 for each protective variant allele. Results were similar in both Stage III (OS: aHR = 0.70; PFS: aHR = 0.71) and Stage IV patients (OS: aHR = 0.81; PFS: aHR = 0.77). CONCLUSION: A GSV on 5p15.33 is not only a risk factor for lung cancer but may also be associated with survival in patients with late stage NSCLC. If validated, GSVs may define subsets of patients with different risk and prognosis of NSCLC.

Two BRM promoter insertion polymorphisms increase the risk of early-stage upper aerodigestive tract cancers.

Brahma (BRM) has a key function in chromatin remodeling. Two germline BRM promoter insertion-deletion polymorphisms, BRM-741 and BRM-1321, have been previously associated with an increased risk of lung cancer in smokers and head and neck cancer. To further evaluate their role in cancer susceptibility particularly in early disease, we conducted a preplanned case-control study to investigate the association between the BRM promoter variants and stage I/II upper aerodigestive tract (UADT) cancers (i.e., lung, esophageal, head and neck), a group of early-stage malignancies in which molecular and genetic etiologic factors are poorly understood. The effects of various clinical factors on this association were also studied. We analyzed 562 cases of early-stage UADT cancers and 993 matched healthy controls. The double homozygous BRM promoter variants were associated with a significantly increased risk of early stage UADT cancers (adjusted odds ratio [aOR], 2.46; 95% confidence interval [CI], 1.7-3.8). This association was observed in lung (aOR, 2.61; 95% CI, 1.5-4.9) and head and neck (aOR, 2.75; 95% CI, 1.4-5.6) cancers, but not significantly in esophageal cancer (aOR, 1.66; 95% CI, 0.7-5.8). There was a nonsignificant trend for increased risk in the heterozygotes or single homozygotes. The relationship between the BRM polymorphisms and early-stage UADT cancers was independent of age, sex, smoking status, histology, and clinical stage. These findings suggest that the BRM promoter double insertion homozygotes may be associated with an increased risk of early-stage UADT cancers independent of smoking status and histology, which must be further validated in other populations.

Second-hand smoke as a predictor of smoking cessation among lung cancer survivors.

PURPOSE: Second-hand smoke (SHS; ie, exposure to smoking of friends and spouses in the household) reduces the likelihood of smoking cessation in noncancer populations. We assessed whether SHS is associated with cessation rates in lung cancer survivors. PATIENTS AND METHODS: Patients with lung cancer were recruited from Princess Margaret Cancer Centre, Toronto, ON, Canada. Multivariable logistic regression and Cox proportional hazard models evaluated the association of sociodemographics, clinicopathologic variables, and SHS with either smoking cessation or time to quitting. RESULTS: In all, 721 patients completed baseline and follow-up questionnaires with a mean follow-up time of 54 months. Of the 242 current smokers at diagnosis, 136 (56%) had quit 1 year after diagnosis. Exposure to smoking at home (adjusted odds ratio [aOR], 6.18; 95% CI, 2.83 to 13.5; P < .001), spousal smoking (aOR, 6.01; 95% CI, 2.63 to 13.8; P < .001), and peer smoking (aOR, 2.49; 95% CI, 1.33 to 4.66; P = .0043) were each associated with decreased rates of cessation. Individuals exposed to smoking in all three settings had the lowest chances of quitting (aOR, 9.57; 95% CI, 2.50 to 36.64; P < .001). Results were similar in time-to-quitting analysis, in which 68% of patients who eventually quit did so within 6 months after cancer diagnosis. Subgroup analysis revealed similar associations across early- and late-stage patients and between sexes. CONCLUSION: SHS is an important factor associated with smoking cessation in lung cancer survivors of all stages and should be a key consideration when developing smoking cessation programs for patients with lung cancer.

Impact and feasibility of a comprehensive geriatric assessment in the oncology setting: a pilot study.

OBJECTIVES: A comprehensive geriatric assessment (CGA) is an objective means of assessing the global health of older patients. While evidence suggesting its promise in improving outcome prediction in the oncology setting is growing, its benefit in guiding treatment decisions remains uncertain. We sought to determine the feasibility and impact of CGA, from a consultative geriatric-oncology service, on treatment decisions in older cancer patients. METHODS: A pilot clinic, where patients underwent CGA with a medical oncologist and geriatrician, was established. Patients ≥70 years, with gastrointestinal or lung cancer were eligible. Following standard assessment by the primary oncologist, a treatment decision was recorded. Patients subsequently underwent a CGA. The final treatment plan was made by the primary oncologist after receipt of findings and recommendations from the CGA. Changes in treatment decisions were recorded. RESULTS: The study enrolled from January to October 2009. Of 168 eligible patients, 120 (71%) were not referred for assessment. Thirty of 48 patients approached underwent CGA. In six patients the treatment plan was undecided at time of referral. In five of these, CGA impacted the ultimate decision (83%). Where the management plan was decided at time of referral (n=24), CGA impacted the final decision in only 1 patient (4%). Previously unidentified medical problems were identified in 70% of patients. CONCLUSIONS: Several factors limited the feasibility of a consultation-type geriatric-oncology service to assess older cancer patients. The impact of CGA in informing treatment decisions was modest but may be of value when the initial treatment decision is uncertain.