Salgado-Montilla Jeannette L, Rodríguez-Cabán Jorge L, Sánchez-García Jonathan, Sánchez-Ortiz Ricardo, Irizarry-Ramírez Margarita
University of Puerto Rico/MD Anderson Cancer Center Partnership for Excellence in Cancer Research, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico, USA.
School of Health Professions, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico, USA.
Arch Cancer Res. 2017;5(3). doi: 10.21767/2254-6081.1000148. Epub 2017 Aug 22.
Obesity is prevalent in PR and has been associated with prostate cancer (PCa) mortality and aggressiveness. Polymorphisms (SNPs) and in the FTO gene have been associated with both obesity and PCa. The aim of this work was to ascertain whether the presence of these SNPs is associated with PCa risk and severity in a cohort of Puerto Rican men.
The study population consisted of 513 Puerto Rican men age ranging from 40-79 years old who underwent radical prostatectomy (RP) as the first treatment for PCa and 128 healthy Puerto Rican men age ranging from 40-79 years old. Genomic DNA (gDNA) was extracted and SNPs were determined by Real-Time PCR. PCa severity was defined based on RP stage and Gleason Score. The relationship of FTO SNPs with demographic, clinical characteristics, PCa status and PCa severity were assessed. Logistic regression models with a 95% confidence interval (CI) determined SNPs interaction with PCa risk and severity odds ratio (ORs).
BMI, age and PSA were considered as confounders. Hardy-Weinberg equilibrium was present for both SNPs. The heterozygous forms () were the most prevalent genotypes and the frequency of alleles and genotypes for both SNPs agreed with those published in 1000 genomes. Results suggest an inverse association between the mutated and the risk of having PCa (OR: 0.53, 95% CI: 0.31-0.92) and a positive association with overweight (OR: 1.05, 95% CI: 0.68-1.62). Importantly, among the cases that were overweight, those with mutated had a greater chance of high severity PCa (OR: 1.39, 95% CI: 0.84-2.32) although these results were not statistical significant upon adjustment. Limitations of the study were the relatively small cohort and lack of access to the weight history of all our subjects.
Results offer a research line to be followed with an expanded number of subjects that may provide a better statistical significance, to unravel the high mortality rate in this population.
肥胖在波多黎各很普遍，并且与前列腺癌（PCa）的死亡率和侵袭性有关。FTO基因中的多态性（单核苷酸多态性，SNPs）与肥胖和PCa均有关联。这项研究的目的是确定在一组波多黎各男性中，这些SNPs的存在是否与PCa风险及严重程度相关。
研究人群包括513名年龄在40 - 79岁之间、接受根治性前列腺切除术（RP）作为PCa首次治疗的波多黎各男性，以及128名年龄在40 - 79岁之间的健康波多黎各男性。提取基因组DNA（gDNA），通过实时聚合酶链反应确定SNPs。根据RP分期和 Gleason评分定义PCa严重程度。评估FTO SNPs与人口统计学、临床特征、PCa状态及PCa严重程度之间的关系。采用95%置信区间（CI）的逻辑回归模型确定SNPs与PCa风险及严重程度优势比（ORs）的相互作用。
体重指数（BMI）、年龄和前列腺特异性抗原（PSA）被视为混杂因素。两个SNPs均符合哈迪 - 温伯格平衡。杂合形式（）是最常见的基因型，两个SNPs的等位基因和基因型频率与千人基因组计划中公布的一致。结果表明，突变型与患PCa的风险呈负相关（OR：0.53，95%CI：0.31 - 0.92），与超重呈正相关（OR：1.05，95%CI：0.68 - 1.62）。重要的是，在超重的病例中，携带突变型的患者患高严重程度PCa的可能性更大（OR：1.39，95%CI：0.84 - 2.32），尽管调整后这些结果无统计学意义。本研究的局限性在于队列相对较小，且无法获取所有受试者的体重史。
研究结果为后续研究提供了一个方向，即增加受试者数量，这可能会提供更好的统计学意义，以阐明该人群的高死亡率。
