Skibola Christine F, Bracci Paige M, Paynter Randi A, Forrest Matthew S, Agana Luz, Woodage Trevor, Guegler Karl, Smith Martyn T, Holly Elizabeth A
Division of Environmental Health Sciences, School of Public Health, 140 Earl Warren Hall, University of California, Berkeley, CA 94720-7360, USA.
Cancer Epidemiol Biomarkers Prev. 2005 Oct;14(10):2391-401. doi: 10.1158/1055-9965.EPI-05-0343.
Expression of prolactin and of prolactin and estrogen receptors in lymphocytes, bone marrow, and lymphoma cell lines suggests that hormonal modulation may influence lymphoma risk. Prolactin and estrogen promote the proliferation and survival of B cells, factors that may increase non-Hodgkin lymphoma risk, and effects of estrogen may be modified by catechol-O-methyltransferase (COMT), an enzyme that alters estrogenic activity. Cytochrome P450 17A1 (CYP17A1), a key enzyme in estrogen biosynthesis, has been associated with increased cancer risk and may affect lymphoma susceptibility. We studied the polymorphisms prolactin (PRL) -1149G>T, CYP17A1 -34T>C, and COMT 108/158Val>Met, and predicted haplotypes among a subset of participants (n = 308 cases, n = 684 controls) in a San Francisco Bay Area population-based non-Hodgkin lymphoma study (n = 1,593 cases, n = 2,515 controls) conducted from 1988 to 1995. Oral contraceptive and other hormone use also was analyzed. Odds ratios (OR) for non-Hodgkin lymphoma and follicular lymphoma were reduced for carriers of the PRL -1149TT genotype [OR, 0.64; 95% confidence interval (95% CI), 0.41-1.0; OR, 0.53; 95% CI, 0.26-1.0, respectively]. Diffuse large-cell lymphoma risk was increased for those with CYP17A1 polymorphisms including CYP17A1 -34CC (OR, 2.0; 95% CI, 1.1-3.5). ORs for all non-Hodgkin lymphoma and follicular lymphoma among women were decreased for COMT IVS1 701A>G [rs737865; variant allele: OR, 0.53; 95% CI, 0.34-0.82; OR, 0.42; 95% CI, 0.23-0.78, respectively]. Compared with never users of oral contraceptives, a 35% reduced risk was observed among oral contraceptive users in the total population. Reduced ORs for all non-Hodgkin lymphoma were observed with use of exogenous estrogens among genotyped women although 95% CIs included unity. These results suggest that PRL, CYP17A1, and COMT may be relevant genetic loci for non-Hodgkin lymphoma and indicate a possible role for prolactin and estrogen in lymphoma pathogenesis.
催乳素以及催乳素和雌激素受体在淋巴细胞、骨髓和淋巴瘤细胞系中的表达表明，激素调节可能会影响淋巴瘤风险。催乳素和雌激素可促进B细胞的增殖和存活，这些因素可能会增加非霍奇金淋巴瘤风险，而雌激素的作用可能会被儿茶酚-O-甲基转移酶（COMT）改变，COMT是一种可改变雌激素活性的酶。细胞色素P450 17A1（CYP17A1）是雌激素生物合成中的关键酶，与癌症风险增加有关，可能会影响淋巴瘤易感性。我们在一项于1988年至1995年开展的旧金山湾区基于人群的非霍奇金淋巴瘤研究（共1593例病例，2515例对照）中的一部分参与者（308例病例，684例对照）中，研究了催乳素（PRL）-1149G>T、CYP17A1 -34T>C和COMT 108/158Val>Met多态性以及预测单倍型。还分析了口服避孕药和其他激素的使用情况。PRL -1149TT基因型携带者患非霍奇金淋巴瘤和滤泡性淋巴瘤的比值比（OR）降低[OR分别为0.64；95%置信区间（95%CI），0.41 - 1.0；OR为0.53；95%CI，0.26 - 1.0]。对于具有CYP17A1多态性（包括CYP17A1 -34CC）的个体，弥漫性大细胞淋巴瘤风险增加（OR，2.0；95%CI，1.1 - 3.5）。COMT IVS1 701A>G[rs737865；变异等位基因：OR分别为0.53；95%CI，0.34 - 0.82；OR为0.42；95%CI，0.23 - 0.78]时，女性中所有非霍奇金淋巴瘤和滤泡性淋巴瘤的OR降低。与从未使用口服避孕药者相比，总体人群中口服避孕药使用者的风险降低了35%。在基因分型女性中，使用外源性雌激素可观察到所有非霍奇金淋巴瘤的OR降低，尽管95%CI包含1。这些结果表明，PRL、CYP17A1和COMT可能是非霍奇金淋巴瘤的相关基因位点，并表明催乳素和雌激素在淋巴瘤发病机制中可能发挥作用。
