Nasr Rami, Temraz Sally, Mukherji Deborah, Shamseddine Ali, Akika Reem, Abbasi Sehrish, Khauli Raja, Bulbul Muhammad, Tamim Hani, Zgheib Nathalie K
Division of Urology, Department of Surgery, American University of Beirut Faculty of Medicine, Beirut, Lebanon. Email:
Asian Pac J Cancer Prev. 2017 Sep 27;18(9):2561-2568. doi: 10.22034/APJCP.2017.18.9.2561.
Background: In Lebanon, bladder cancer (BC) has an unusually high prevalence. Individuals who are exposed to aromatic amines from smoking or certain occupations and carrying the slow N-acetyl transferase 2 (NAT2) acetylator’ phenotype may be at a higher risk. Methods: Data and DNA from 115 Lebanese BC cases and 306 controls were examined. Ten NAT2 single nucleotide polymorphisms were genotyped, seven of which were then included in haplotype and phenotype analysis. Results: BC patients were more likely to be males (87.8% vs. 54.9%) and current smokers (60.9% vs. 26.5%) when compared to controls. In both groups, most participants had the slow NAT2 acetylator phenotype (66.1% of BC cases vs 62.7% of controls; P=0.302) with the NAT2*5B and *6A haplotypes being the most common. The odds ratio (95%CI) of having BC among slow NAT2 acetylators was 1.157 (0.738-1.815) and remained non-significant after adjustment [1.097 (0.666-1.806)]. Sensitivity analysis with a subgroup of 113 cases and 84 controls for which occupational history was available revealed a statistically significant association between slow NAT2 acetylators and BC in females only. The sample size was however very small and the CI quite wide. Conclusions: This is the first study to evaluate the distribution of NAT2 haplotypes and their potential role in BC in a Lebanese population. The absence of any significant association may be due to the relatively small sample size, the unavailability of matching by gender, and the lack of evaluation of genetic interactions with extent of active and passive smoking, exposure to environmental pollutants, diet, and other genes. The potential association limited to females needs further evaluation.
在黎巴嫩，膀胱癌（BC）的患病率异常高。因吸烟或某些职业接触芳香胺且携带慢乙酰化型N - 乙酰基转移酶2（NAT2）表型的个体可能面临更高风险。方法：对115例黎巴嫩膀胱癌患者和306例对照的数据及DNA进行检测。对10个NAT2单核苷酸多态性进行基因分型，其中7个随后纳入单倍型和表型分析。结果：与对照组相比，膀胱癌患者男性比例更高（87.8%对54.9%）且当前吸烟者比例更高（60.9%对26.5%）。在两组中，大多数参与者具有慢NAT2乙酰化型表型（膀胱癌患者中66.1%，对照组中62.7%；P = 0.302），其中NAT25B和6A单倍型最为常见。慢NAT2乙酰化者患膀胱癌的比值比（95%置信区间）为1.157（0.738 - 1.815），调整后仍无统计学意义[1.097（0.666 - 1.806）]。对有职业史的113例病例和84例对照亚组进行的敏感性分析显示，仅在女性中慢NAT2乙酰化者与膀胱癌之间存在统计学显著关联。然而样本量非常小且置信区间很宽。结论：这是第一项评估黎巴嫩人群中NAT2单倍型分布及其在膀胱癌中潜在作用的研究。未发现任何显著关联可能是由于样本量相对较小、缺乏按性别匹配以及未评估与主动和被动吸烟程度、环境污染物暴露、饮食及其他基因的遗传相互作用。仅限于女性的潜在关联需要进一步评估。
