香烟烟雾中含有约50种致癌物质和前致癌物。最著名的前致癌物质是多环芳香烃和芳香胺。[12]Hecht SS. Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst. 1999;91:1194-1210.http://jnci.oxfordjournals.org/cgi/content/full/91/14/1194http://www.ncbi.nlm.nih.gov/pubmed/10413421?tool=bestpractice.com大多数致癌物质和前致癌物需要通过代谢酶如细胞色素P450激活。其他的酶有助于分解致癌物质如谷胱甘肽-S-转移酶。
酒精引起的致癌作用是通过乙醛介导的。[13]Baan R, Straif K, Grosse Y, et al. Carcinogenicity of alcoholic beverages. Lancet Oncol. 2007;8:292-293.http://www.ncbi.nlm.nih.gov/pubmed/17431955?tool=bestpractice.com直接暴露于酒精的部位,如口咽和喉咽部,存在罹患癌症的风险。由于累及部位均可能罹患癌症,吸烟和饮酒者还存在发生第二原发癌的危险。乙醇脱氢酶激活乙醛,乙醛脱氢酶分解其毒性。对这些致癌物质和前致癌物的个体易感性被认为是继发于这些酶的遗传多态性。[14]Hashibe M, Brennan P, Strange RC, et al. Meta- and pooled analyses of GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes and risk of head and neck cancer. Cancer Epidemiol Biomarkers Prev. 2003;12:1509-1517.http://cebp.aacrjournals.org/cgi/content/full/12/12/1509http://www.ncbi.nlm.nih.gov/pubmed/14693745?tool=bestpractice.com
HPV的致癌作用尚不清楚,目前被认为是病毒灭活抑癌基因p53所致。[15]Wang X, Wang HK, McCoy JP, et al. Oncogenic HPV infection interrupts the expression of tumor-suppressive miR-34a through viral oncoprotein E6. RNA. 2009;15:637-647.http://rnajournal.cshlp.org/content/15/4/637.longhttp://www.ncbi.nlm.nih.gov/pubmed/19258450?tool=bestpractice.com
亚硝胺是无烟烟草的主要致癌物。[16]Boffetta P, Hecht S, Gray N, et al. Smokeless tobacco and cancer. Lancet Oncol. 2008;9:667-675.http://www.ncbi.nlm.nih.gov/pubmed/18598931?tool=bestpractice.com
槟榔碱是槟榔的主要致癌物。[17]Chen YJ, Chang JT, Liao CT, et al. Head and neck cancer in the betel quid chewing area: recent advances in molecular carcinogenesis. Cancer Sci. 2008;99:1507-1514.http://www3.interscience.wiley.com/cgi-bin/fulltext/121378170/HTMLSTARThttp://www.ncbi.nlm.nih.gov/pubmed/18754860?tool=bestpractice.com