Abstract:
Our understanding of risk factors for the development of chronic lymphocytic leukemia (CLL) is still incomplete and includes genetic and environmental factors. CLL is one of the most familial of all cancers, yet common high-penetrance risk alleles have not been identified. Genome-wide association studies have identified many common variants with low relative risks, whereas exome-wide rare variant analysis has implicated ATM in CLL causation. Environmental factors have also been challenging to identify given the limited understanding of the relevant time period of exposure relative to diagnosis, and the inability to quantify past exposures. Agent Orange and glyphosate herbicides have perhaps the most data to support their role. CLL is preceded by a precursor condition called monoclonal B-cell lymphocytosis (MBL), which could therefore be considered a risk factor, but which itself is likely caused by the same risk factors that ultimately give rise to CLL. Although virtually all people with CLL have a preceding MBL phase, most people with MBL will not develop CLL.
摘要:
我们对慢性淋巴细胞白血病(CLL)发展的危险因素的理解仍然不完整,包括遗传和环境因素。CLL是所有癌症中家族性最强的癌症之一,然而常见的高外显率风险等位基因尚未确定。全基因组关联研究已经确定了许多相对风险较低的常见变异,而全外显子组罕见变异分析则暗示ATM与CLL因果关系有关。环境因素也具有挑战性,以确定相对于诊断的相关暴露时间段的了解有限,以及无法量化过去的风险敞口。橙剂和草甘膦除草剂可能有最多的数据来支持它们的作用。CLL之前是一种称为单克隆B细胞淋巴细胞增多症(MBL)的前体疾病,因此,这可以被认为是一个风险因素,但这本身很可能是由最终导致CLL的相同风险因素引起的。尽管几乎所有患有CLL的人都有之前的MBL阶段,大多数MBL患者不会发展CLL。