复旦大学遗传工程实验室卢大儒教授联合美国研究人员在《癌症》期刊撰文指出，两种基因的变异可能是导致中国人更易罹患肺癌的原因。
研究人员此前认为，ABCB1和ABCC1两种基因的作用是去除肺部的致癌物质，防止吸入毒素导致肺癌。
在本次研究中，研究者分析了中国东南部500名肺癌患者和517名未患肺癌者的基因，并在声明中写道：“某些基因变异在肺癌患者身上发生的概率比未患癌症者身上大得多。”
在肺癌患者中，31%的人ABCB1基因发生某种变异，27%的人ABCC1基因发生变异。而非癌症患者中，这两种基因发生变异的概率则分别只有15%和12%。
研究人员称：“ABCB1的变异尤其会使女性和60岁以下人群罹患癌症的几率升高。它还与一种常见肺癌--腺癌（adenocarcinoma）直接相关。”（生物谷Bioon.com）
生物谷推荐原始出处：
Cancer 23 Dec 2008 DOI 10.1002/cncr.24042
Genetic susceptibility of lung cancer associated with common variants in the 3 untranslated regions of the adenosine triphosphate-binding cassette B1 (ABCB1) and ABCC1 candidate transporter genes for carcinogen export
Haijian Wang, PhD 1 2, Guangfu Jin, PhD 3, Haifeng Wang, PhD 4, Gaifen Liu, PhD 5, Ji Qian, MS 1, Li Jin, PhD 1, Qingyi Wei, MD, PhD 6, Hongbing Shen, MD, PhD 3, Wei Huang, MD, PhD 4, Daru Lu, PhD 1 *
1State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China
2The Simons Center for Systems Biology, School of Natural Sciences, Institute for Advanced Study, Princeton, New Jersey
3Department of Epidemiology and Biostatistics, Cancer Research Center, Nanjing Medical University, Nanjing, China
4Department of Genetics, Chinese National Human Genome Center at Shanghai, Shanghai, China
5Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, Groningen, the Netherlands
6Department of Epidemiology, the University of Texas M. D. Anderson Cancer Center, Houston, Texas
*Correspondence to Daru Lu, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China
ABSTRACT
BACKGROUND:
Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NKK) is a well defined carcinogen that can induce lung cancer. Genetic polymorphisms in its disposition pathways could modify the risk of developing lung cancer. The authors of this report previously catalogued the sequence variations of the adenosine triphosphate-binding cassette B1 (ABCB1) and ABCC1 candidate transporter genes for carcinogen export in the Chinese population and screened out common variants with potential function in their 5 flanking and 3 untranslated regions. The objective of the current study was to test the hypothesis that these common variants are associated with lung cancer risk.
METHODS:
The genotyping analyses for 6 common regulatory variants (reference single-nucleotide polymorphism 4728709 [rs4728709] and rs2188524 in the 5 flanking region of ABCB1 and rs3842 in its 3untranslated region; rs3743527, rs212090, and rs212091 in the 3 untranslated region of ABCC1) was conducted in a case-control study of 500 patients with incident lung cancer and 517 cancer-free controls in a Chinese population.
RESULTS:
Compared with the wild adenosine/adenosine (A/A) genotype, the variant rs3842 genotype (adenosine/guanosine [A/G] + G/G) of ABCB1 was associated with a statistically significant increased risk of developing lung cancer (odds ratio [OR]. 1.36; 95% confidence interval [95% CI], 1.06-1.76). Also evident was the association between cancer susceptibility and the variant rs212090 genotype (adenosine/thymidine [A/T] + T/T) of ABCC1 (OR, 1.37; 95% CI, 1.03-1.83). Haplotype-based association analysis also emphasized that 2 common haplotypes carrying the culprit alleles of the 2 single-nucleotide polymorphisms were associated with an increased risk of cancer. In addition, stratification analysis demonstrated a remarkable association of ABCB1 rs3842 with the risk of cancer manifested in women (OR, 2.57; 95% CI, 1.36-4.85), in the histologic type of adenocarcinoma (OR, 1.42; 95% CI, 1.03-1.99), and in individuals aged <60 years (OR, 1.50; 95% CI, 1.05-2.14).
CONCLUSIONS:
The current study demonstrated that common polymorphisms in the 3 untranslated region of ABCB1 and ABCC1 may contribute to the etiology of lung cancer, providing further support for the hypothesis that genetic components in the metabolism and the disposition of NNK may modify the risk of lung cancer, especially in lung adenocarcinoma among women. Functional studies are warranted to elucidate whether aberrant expression and dysfunction of ABC transporters for carcinogen export may play a role in the development of lung cancer. Cancer 2009. ? 2008 American Cancer Society.
