Department of Community Medicine and Epidemiology, Carmel Medical Center, 7 Michal Street, Haifa 34362, Israel.
Cancer. 2012 Apr 15;118(8):1989-93. doi: 10.1002/cncr.26506. Epub 2011 Sep 22.
Variants of the mutY homolog gene MutYH, a DNA repair gene, are associated with increased risk of colorectal cancer; however, it remains unclear whether these variants also are associated with the risk of other cancers. The authors studied the risk of breast cancer associated with MutYH variants in a unique ethnic group of Sephardi Jews in Israel with a high prevalence of MutYH mutations.
The study participants were 930 Sephardi Jewish women of North African origin who were recruited into the population-based case-control Breast Cancer in Northern Israel Study (BCINIS) either as breast cancer cases or as healthy controls. All participants contributed a blood sample and completed an interview. Two MutYH variants, a glycine-to-aspartic acid substitution at codon 396 (G396D) and a tyrosine-to-cysteine substitution at codon 179 (Y179C), were studied.
In the Sephardi Jews, among the healthy controls, 20 women (3.7%) were homozygote or heterozygote carriers of the G396D variant, and 4 women (0.7%) were heterozygote carriers of the Y179C variant. Breast cancer cases had a 6.7% prevalence of G396D, yielding a significantly elevated risk estimate for breast cancer (odds ratio, 1.86; 95% confidence interval, 1.02-3.39; P = .039). The tumors detected in carriers with MutYH variants were similar in characteristics to those without MutYH variants, as was the age at diagnosis.
Carriers of variants in MutYH, although not very common, may have an increased risk of breast cancer in Jews of North African origin. Identification of such carriers and special surveillance protocols may be warranted.
MutY 同源物基因 MutYH 的变体是一种 DNA 修复基因，与结直肠癌风险增加相关；然而，这些变体是否也与其他癌症的风险相关尚不清楚。作者在以色列一个具有高 MutYH 突变流行率的独特的北非裔塞法迪犹太人族群中，研究了 MutYH 变体与乳腺癌风险的相关性。
本研究的参与者是 930 名来自北非的塞法迪犹太裔女性，她们是基于人群的以色列北部乳腺癌病例对照研究（BCINIS）的一部分，要么作为乳腺癌病例，要么作为健康对照。所有参与者均提供了血液样本并完成了访谈。研究了两个 MutYH 变体，一个是第 396 位密码子的甘氨酸-天冬氨酸取代（G396D），另一个是第 179 位密码子的酪氨酸-半胱氨酸取代（Y179C）。
在塞法迪犹太人中，在健康对照组中，有 20 名女性（3.7%）是 G396D 变体的纯合子或杂合子携带者，有 4 名女性（0.7%）是 Y179C 变体的杂合子携带者。乳腺癌病例的 G396D 检出率为 6.7%，乳腺癌风险显著升高（比值比，1.86；95%置信区间，1.02-3.39；P =.039）。携带 MutYH 变体的患者的肿瘤与不携带 MutYH 变体的患者的肿瘤在特征上相似，诊断时的年龄也相似。
MutYH 变体的携带者虽然并不常见，但北非裔犹太人可能有更高的乳腺癌风险。可能需要识别这些携带者并制定特殊的监测方案。
