Höhne Svetlana, Gerullis Holger, Blaszkewicz Meinolf, Selinski Silvia, Hengstler Jan G, Otto Thomas, Golka Klaus
a Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo) , Dortmund , Germany.
b Department of Urology , Lukas Hospital , Neuss , Germany.
J Toxicol Environ Health A. 2017;80(7-8):417-422. doi: 10.1080/10937404.2017.1304727. Epub 2017 Jul 11.
In a large bladder cancer study in the greater Berlin area with 425 cases and 343 controls, the haplotype N-acetyltransferase 110 (NAT110) was associated with a decreased bladder cancer risk. In a recently published meta-analysis, results of the studies were found to be inconclusive. Therefore, the aim of this study was to investigate the frequency of NAT110 in bladder cancer patients and controls recruited in an area without industries reported to be associated with increased bladder cancer risk. Rs1057126 (1088 T > A) and rs15561 (1095 C > A) were determined in 412 bladder cancer patients and 415 controls without a known history of malignancies. With these two single-nucleotide polymorphisms (SNP), it was possible to distinguish between NAT14 (wild type), NAT13 (1095 C > A), and NAT110 (1088 T > A, 1095C > A). The frequencies of the determined NAT1 haplotypes did not differ markedly between cases and controls: NAT14: 74%, NAT13: 6%, NAT110: 20%. Bladder cancer risk was not significantly modulated by NAT110/10 (OR 1.03, 95% CI 0.71-1.48) but was higher for NAT13/3 genotypes (OR 2.05, 95% CI 1.32-3.21). In contrast to the Berlin study from 2001, data in present study demonstrated that NAT110 haplotype was not associated with a significantly decreased bladder cancer risk. This may be due to local effects in the greater Berlin area, particularly at the time of investigation. The findings of the present study are in agreement with observations of a recently published meta-analysis which also showed no relevant impact of NAT110 haplotype on bladder cancer risk. The impact of the rare NAT13/*3 genotype was significant but this may be attributed to rarity without major practical relevance.
在大柏林地区开展的一项针对425例膀胱癌患者及343名对照的大型研究中,单倍型N - 乙酰基转移酶110(NAT110)与膀胱癌风险降低相关。在最近发表的一项荟萃分析中,研究结果尚无定论。因此,本研究的目的是调查在一个无据报道与膀胱癌风险增加相关行业的地区招募的膀胱癌患者及对照中NAT110的频率。在412例膀胱癌患者和415名无已知恶性肿瘤病史的对照中测定了rs1057126(1088 T>A)和rs15561(1095 C>A)。通过这两个单核苷酸多态性(SNP),可以区分NAT14(野生型)、NAT13(1095 C>A)和NAT110(1088 T>A,1095C>A)。所测定的NAT1单倍型频率在病例组和对照组之间无明显差异:NAT14:74%,NAT13:6%,NAT110:20%。NAT110/10对膀胱癌风险无显著调节作用(OR 1.03,95%CI 0.71 - 1.48),但NAT13/3基因型的风险更高(OR 2.05,95%CI 1.32 - 3.21)。与20年的柏林研究不同,本研究数据表明NAT110单倍型与膀胱癌风险显著降低无关。这可能是由于大柏林地区的局部影响,尤其是在调查时。本研究结果与最近发表的一项荟萃分析的观察结果一致,该分析也表明NAT110单倍型对膀胱癌风险无相关影响。罕见的NAT13/*3基因型的影响显著,但这可能归因于其罕见性,而无重大实际意义。