All Title Author
Keywords Abstract

PLOS ONE  2009 

Is Genetic Background Important in Lung Cancer Survival?

DOI: 10.1371/journal.pone.0005588

Full-Text   Cite this paper   Add to My Lib

Abstract:

Background In lung cancer, a patient's survival is poor with a wide variation in survival within the stage of disease. The aim of this study was to investigate the familial concordance in lung cancer survival by means of analyses of pairs with different degrees of familial relationships. Methods Our population-based Swedish family database included three million families and over 58 100 lung cancer patients. We modelled the proband (parent, sibling, spouse) survival utilizing a multivariate proportional hazard (Cox) model adjusting for possible confounders of survival. Subsequently, the survival in proband's relative (child, sibling, spouse) was analysed with a Cox model. Findings By use of Cox modelling with 5 years follow-up, we noted a decreased hazard ratio for death in children with good parental survival (Hazard Ratio [HR] = 0.71, 95% CI = 0.51 to 0.99), compared to those with poor parental survival. Also for siblings, a very strong protective effect was seen (HR = 0.14, 95% CI = 0.030 to 0.65). Finally, in spouses no correlation in survival was found. Interpretation Our findings suggest that genetic factors are important in lung cancer survival. In a clinical setting, information on prognosis in a relative may be vital in foreseeing the survival in an individual newly diagnosed with lung cancer. Future molecular studies enhancing the understanding of the underlying mechanisms and pathways are needed.

References

[1]  Hoffman PC, Mauer AM, Vokes EE (2000) Lung cancer. Lancet 355: 479–485.
[2]  Jemal A, Clegg LX, Ward E, Ries LA, Wu X, et al. (2004) Annual report to the nation on the status of cancer, 1975–2001, with a special feature regarding survival. Cancer 101: 3–27.
[3]  Jemal A, Siegel R, Ward E, Murray T, Xu J, et al. (2007) Cancer statistics, 2007. CA Cancer J Clin 57: 43–66.
[4]  Hunter K, Welch DR, Liu ET (2003) Genetic background is an important determinant of metastatic potential. Nat Genet 34: 23–24; author reply 25.
[5]  Hunter KW (2003) Allelic diversity in the host genetic background may be an important determinant in tumor metastatic dissemination. Cancer Lett 200: 97–105.
[6]  Lifsted T, Le Voyer T, Williams M, Muller W, Klein-Szanto A, et al. (1998) Identification of inbred mouse strains harboring genetic modifiers of mammary tumor age of onset and metastatic progression. Int J Cancer 77: 640–644.
[7]  Welch DR, Hunter KW (2003) A new member of the growing family of metastasis suppressors identified in prostate cancer. J Natl Cancer Inst 95: 839–841.
[8]  Yoon SM, Hong YC, Park HJ, Lee JE, Kim SY, et al. (2005) The polymorphism and haplotypes of XRCC1 and survival of non-small-cell lung cancer after radiotherapy. Int J Radiat Oncol Biol Phys 63: 885–891.
[9]  Liu G, Zhou W, Christiani DC (2005) Molecular epidemiology of non-small cell lung cancer. Semin Respir Crit Care Med 26: 265–272.
[10]  Pine SR, Mechanic LE, Ambs S, Bowman ED, Chanock SJ, et al. (2007) Lung cancer survival and functional polymorphisms in MBL2, an innate-immunity gene. J Natl Cancer Inst 99: 1401–1409.
[11]  Dubey S, Stephenson P, Levy DE, Miller JA, Keller SM, et al. (2006) EGFR dinucleotide repeat polymorphism as a prognostic indicator in non-small cell lung cancer. J Thorac Oncol 1: 406–412.
[12]  Sun T, Gao Y, Tan W, Ma S, Zhang X, et al. (2006) Haplotypes in matrix metalloproteinase gene cluster on chromosome 11q22 contribute to the risk of lung cancer development and progression. Clin Cancer Res 12: 7009–7017.
[13]  Lindstrom LS, Hall P, Hartman M, Wiklund F, Gronberg H, et al. (2007) Familial concordance in cancer survival: a Swedish population-based study. Lancet Oncol 8: 1001–1006.
[14]  Zhou W, Heist RS, Liu G, Park S, Neuberg DS, et al. (2006) Smoking cessation before diagnosis and survival in early stage non-small cell lung cancer patients. Lung Cancer 53: 375–380.
[15]  Ebbert JO, Williams BA, Sun Z, Aubry MC, Wampfler JA, et al. (2005) Duration of smoking abstinence as a predictor for non-small-cell lung cancer survival in women. Lung Cancer 47: 165–172.
[16]  Tammemagi CM, Neslund-Dudas C, Simoff M, Kvale P (2004) Smoking and lung cancer survival: the role of comorbidity and treatment. Chest 125: 27–37.
[17]  Macintyre S, Sooman A (1991) Non-paternity and prenatal genetic screening. Lancet 338: 869–871.
[18]  Sykes B, Irven C (2000) Surnames and the Y chromosome. Am J Hum Genet 66: 1417–1419.
[19]  Center for Epidemiology Cancer incidence in Sweden 2000; Stockholm:The National Board of Health and Welfare, 2002.
[20]  de Faire U, Friberg L, Lorich U, Lundman T (1976) A validation of cause-of-death certification in 1,156 deaths. Acta Med Scand 200: 223–228.
[21]  Larsson LG, Nystrom L, Wall S, Rutqvist L, Andersson I, et al. (1996) The Swedish randomised mammography screening trials: analysis of their effect on the breast cancer related excess mortality. J Med Screen 3: 129–132.
[22]  Rutqvist LE (1985) Validity of certified causes of death in breast carcinoma patients. Acta Radiol Oncol 24: 385–390.
[23]  Schoenfeld D (1982) Partial residuals for the proportional hazards regression model. Biometrika 69: 239–241.
[24]  Cancer i siffror (2005) - Popul?rvetenskapliga fakta om cancer. Stockholm (Sverige): Wassberg Skotte AB.
[25]  Yoshino I, Maehara Y (2007) Impact of smoking status on the biological behavior of lung cancer. Surg Today 37: 725–734.
[26]  Lorenzo Bermejo J, Hemminki K (2005) Familial lung cancer and aggregation of smoking habits: a simulation of the effect of shared environmental factors on the familial risk of cancer. Cancer Epidemiol Biomarkers Prev 14: 1738–1740.
[27]  Bricker JB, Peterson AV Jr, Leroux BG, Andersen MR, Rajan KB, et al. (2006) Prospective prediction of children's smoking transitions: role of parents' and older siblings' smoking. Addiction 101: 128–136.
[28]  Griesbach D, Amos A, Currie C (2003) Adolescent smoking and family structure in Europe. Soc Sci Med 56: 41–52.
[29]  West P, Sweeting H, Ecob R (1999) Family and friends' influences on the uptake of regular smoking from mid-adolescence to early adulthood. Addiction 94: 1397–1411.
[30]  Sutton GC (1980) Assortative marriage for smoking habits. Ann Hum Biol 7: 449–456.
[31]  Price RA, Vandenberg SG (1980) Spouse similarity in American and Swedish couples. Behav Genet 10: 59–71.
[32]  Clark AE, Etile F (2006) Don't give up on me baby: spousal correlation in smoking behaviour. J Health Econ 25: 958–978.
[33]  Matakidou A, el Galta R, Webb EL, Rudd MF, Bridle H, et al. (2007) Genetic variation in the DNA repair genes is predictive of outcome in lung cancer. Hum Mol Genet 16: 2333–2340.
[34]  Chen HY, Yu SL, Chen CH, Chang GC, Chen CY, et al. (2007) A five-gene signature and clinical outcome in non-small-cell lung cancer. N Engl J Med 356: 11–20.
[35]  Yang P, Yokomizo A, Tazelaar HD, Marks RS, Lesnick TG, et al. (2002) Genetic determinants of lung cancer short-term survival: the role of glutathione-related genes. Lung Cancer 35: 221–229.
[36]  Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420: 860–867.
[37]  Isla D, Sarries C, Rosell R, Alonso G, Domine M, et al. (2004) Single nucleotide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer. Ann Oncol 15: 1194–1203.

Full-Text

comments powered by Disqus