Bácsi Krisztián, Hitre Erika, Kósa János P, Horváth Henrik, Lazáry Aron, Lakatos Péter L, Balla Bernadett, Budai Barna, Lakatos Péter, Speer Gábor
First Department of Medicine, Semmelweis University, Budapest 1083 Korányi Sándor u 2/a, Hungary.
BMC Cancer. 2008 Nov 3;8:317. doi: 10.1186/1471-2407-8-317.
Epidemiological studies suggested the chemopreventive role of higher calcium intake in colorectal carcinogenesis. We examined genetic polymorphisms that might influence calcium metabolism: lactase (LCT) gene 13910 C/T polymorphism causing lactose intolerance and calcium-sensing receptor (CaSR) gene A986S polymorphism as a responsible factor for the altered cellular calcium sensation.
538 Hungarian subjects were studied: 278 patients with colorectal cancer and 260 healthy controls. Median follow-up was 17 months. After genotyping, the relationship between LCT 13910 C/T and CaSR A986S polymorphisms as well as tumor incidence/progression was investigated.
in patient with colorectal cancer, a significantly higher LCT CC frequency was associated with increased distant disease recurrence (OR = 4.04; 95% CI = 1.71-9.58; p = 0.006). The disease free survival calculated from distant recurrence was reduced for those with LCT CC genotype (log rank test p = 0.008). In case of CaSR A986S polymorphism, the homozygous SS genotype was more frequent in patients than in controls (OR = 4.01; 95% CI = 1.33-12.07; p = 0.014). The number of LCT C and CaSR S risk alleles were correlated with tumor incidence (p = 0.035). The CCSS genotype combination was found only in patients with CRC (p = 0.033).
LCT 13910 C/T and CaSR A986S polymorphisms may have an impact on the progression and/or incidence of CRC.
流行病学研究表明，较高的钙摄入量在结直肠癌发生过程中具有化学预防作用。我们研究了可能影响钙代谢的基因多态性：乳糖酶（LCT）基因13910 C/T多态性导致乳糖不耐受，以及钙敏感受体（CaSR）基因A986S多态性作为细胞钙感觉改变的一个相关因素。
对538名匈牙利受试者进行了研究：278例结直肠癌患者和260名健康对照者。中位随访时间为17个月。基因分型后，研究了LCT 13910 C/T和CaSR A986S多态性与肿瘤发生率/进展之间的关系。
在结直肠癌患者中，LCT基因CC型频率显著升高与远处疾病复发增加相关（OR = 4.04；95% CI = 1.71 - 9.58；p = 0.006）。LCT基因CC基因型患者从远处复发计算的无病生存期缩短（对数秩检验p = 0.008）。对于CaSR A986S多态性，纯合子SS基因型在患者中比在对照者中更常见（OR = 4.01；95% CI = 1.33 - 12.07；p = 0.014）。LCT基因C和CaSR基因S风险等位基因的数量与肿瘤发生率相关（p = 0.035）。CCSS基因型组合仅在结直肠癌患者中发现（p = 0.033）。
LCT 13910 C/T和CaSR A986S多态性可能对结直肠癌的进展和/或发生率有影响。
