Haplotype analysis of the HSD17B1 gene and risk of breast cancer:: A comprehensive approach to multicenter analyses of prospective cohort studies
Haplotype analysis of the HSD17B1 gene and risk of breast cancer:: A comprehensive approach to multicenter analyses of prospective cohort studies
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DOI：
10.1158/0008-5472.can-05-3574
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发表时间：
2006-02-15
期刊：
影响因子：
11.2
通讯作者：
Trichopoulos, D
中科院分区：
文献类型：
--
作者：
Feigelson, HS;Cox, DG;Trichopoulos, D
17 β-羟基类固醇脱氢酶1基因（HSD 17 B1）编码17 HSD 1，其催化雌二醇生物合成的最后一步。尽管HSD 17 B1在激素代谢中起重要作用，但很少有关于HSD 17 B1和乳腺癌的流行病学研究。这项研究包括来自乳腺癌和前列腺癌队列联盟的5个大型队列的5，370例乳腺癌病例和7，480例匹配对照。我们通过对多种族样本进行重测序和密集基因分型来表征HSD 17 B1的变异，并确定了单倍型标记单核苷酸多态性（htSNP），该单倍型标记单核苷酸多态性捕获了HSD 17 B1周围33.3 kb区域内的常见变异。包括先前研究的SNP rs605059（S312 G）在内的四种htSNP在所有病例和对照中被基因分型以标记五种常见的单倍型。条件Logistic回归用于估计疾病的优势比（OR）。我们没有发现常见的HSD 17 B1单倍型或htSNP与乳腺癌总体风险之间存在关联的证据。每种单倍型相对于最常见单倍型的OR范围为0.98至1.07（关联综合检验：X-2 = 3.77，P = 0.58，5个自由度）。当病例按雌激素受体（ER）状态细分时，两种常见的单倍型与ER阴性肿瘤相关（趋势检验，Ps = 0.0009和0.0076; n = 353例）。在白人中常见的HSD 17 B1变异与乳腺癌的总体风险无关;然而，ER阴性肿瘤的子集之间存在相关性。虽然这些ER阴性结果为假阳性结果的概率很高，但这些结果在检查的每个队列中一致，需要进一步研究。
The 17 beta-hydroxysteroid dehydrogenase 1 gene (HSD17B1) encodes 17HSD1, which catalyzes the final step of estradiol biosynthesis. Despite the important role of HSD17B1 in hormone metabolism, few epidemiologic studies of HSD17B1 and breast cancer have been conducted. This study includes 5,370 breast cancer cases and 7,480 matched controls from five large cohorts in the Breast and Prostate Cancer Cohort Consortium. We characterized variation in HSD17B1 by resequencing and dense genotyping a multiethnic sample and identified haplotype-tagging single nucleotide polymorphisms (htSNP) that capture common variation within a 33.3-kb region around HSD17B1. Four htSNPs, including the previously studied SNP rs605059 (S312G), were genotyped to tag five common haplotypes in all cases and controls. Conditional logistic regression was used to estimate odds ratios (OR) for disease. We found no evidence of association between common HSD17B1 haplotypes or htSNPs and overall risk of breast cancer. The OR for each haplotype relative to the most common haplotype ranged from 0.98 to 1.07 (omnibus test for association: X-2 = 3.77, P = 0.58, 5 degrees of freedom). When cases were subdivided by estrogen receptor (ER) status, two common haplotypes were associated with ER-negative tumors (test for trend, Ps = 0.0009 and 0.0076; n = 353 cases). HSD17B1 variants that are common in Caucasians are not associated with overall risk of breast cancer; however, there was an association among the subset of ER-negative tumors. Although the probability that these ER-negative findings are false-positive results is high, these findings were consistent across each cohort examined and warrant further study.