Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas 77005, USA.
Cancer Res. 2010 Mar 15;70(6):2359-67. doi: 10.1158/0008-5472.CAN-09-3096. Epub 2010 Mar 9.
Cigarette smoking is the major cause for lung cancer, but genetic factors also affect susceptibility. We studied families that included multiple relatives affected by lung cancer. Results from linkage analysis showed strong evidence that a region of chromosome 6q affects lung cancer risk. To characterize the effects that this region of chromosome 6q region has on lung cancer risk, we identified a haplotype that segregated with lung cancer. We then performed Cox regression analysis to estimate the differential effects that smoking behaviors have on lung cancer risk according to whether each individual carried a risk-associated haplotype or could not be classified and was assigned unknown haplotypic status. We divided smoking exposures into never smokers, light smokers (<20 pack-years), moderate smokers (20 to <40 pack-years), and heavy smokers (>or=40 pack-years). Comparing results according to smoking behavior stratified by carrier status, compared with never smokers, there was weakly increasing risk for increasing smoking behaviors, with the hazards ratios being 3.44, 4.91, and 5.18, respectively, for light, moderate, or heavy smokers, whereas among the individuals from families without the risk haplotype, the risks associated with smoking increased strongly with exposure, the hazards ratios being, respectively, 4.25, 9.17, and 11.89 for light, moderate, and heavy smokers. The never smoking carriers had a 4.71-fold higher risk than the never smoking individuals without known risk haplotypes. These results identify a region of chromosome 6q that increases risk for lung cancer and that confers particularly higher risks to never and light smokers.
吸烟是肺癌的主要原因，但遗传因素也会影响易感性。我们研究了包括多个受肺癌影响的亲属的家庭。连锁分析的结果表明，染色体 6q 区域强烈影响肺癌风险。为了描述该染色体 6q 区域对肺癌风险的影响，我们确定了与肺癌分离的单倍型。然后，我们进行了 Cox 回归分析，以根据个体是否携带风险相关的单倍型或无法分类且被分配为未知单倍型状态来估计吸烟行为对肺癌风险的差异影响。我们将吸烟暴露分为从不吸烟者、轻度吸烟者（<20 包年）、中度吸烟者（20-<40 包年）和重度吸烟者（>=40 包年）。根据携带状态分层的吸烟行为比较结果，与从不吸烟者相比，随着吸烟行为的增加，风险逐渐增加，危险比分别为 3.44、4.91 和 5.18，分别为轻度、中度或重度吸烟者，而在没有风险单倍型的家庭个体中，与吸烟相关的风险随着暴露的增加而强烈增加，危险比分别为 4.25、9.17 和 11.89，分别为轻度、中度和重度吸烟者。不吸烟的携带者的风险比无已知风险单倍型的不吸烟个体高 4.71 倍。这些结果确定了一个增加肺癌风险的染色体 6q 区域，并且对从不吸烟和轻度吸烟者尤其具有更高的风险。
