Scholarlink

<p>Previous studies have found a markedly reduced risk of cancer among Huntington’s disease (HD) patients with CAG ≥ 40, but data on cancer risk at shorter repeat numbers are lacking. The study includes 8149 subjects from Northern Sweden Health and Disease Study. Genotyping yielded a large number of intermediate allele carriers (IA, CAG<sub>n</sub> 27–35, (<i>n</i> = 497), normal alleles (CAG<sub>n</sub> 17–26,<i>n</i> = 6584), short alleles (CAG ≤ 16, <i>n</i> = 169) and 31 subjects with &gt; 35 repeats, including reduced penetrance alleles (36–39; not guaranteed to suffer HD symptoms during a normal lifespan) and HD alleles &gt; 39. Cancer diagnoses were retrieved from the Swedish Cancer Registry and the Hospital Discharge Registry and death certificates. We used Kaplan-Meier curves and Cox proportional hazard models to estimate the time to cancer, on strata of the population created by CAG repeat number intervals. Smoking status, BMI, as well as alcohol consumption were included in the models. 2735 participants (33.6%) had ≥ 1 cancer type. The Hazard-Ratio (HR) for IA carriers compared with normal alleles was similar, 0.97 CI 0.82–1.15). The reduced penetrance allele group (CAG<sub>n</sub> 36–39, <i>n</i> = 29) had HR of 0.54 CI 0.22–1.30 similar to what has been reported with a full penetrance allele. Intermediate allele carriers as a group did not have a reduced risk of cancer. It remains possible that reduced penetrance alleles confer lower risk of cancer, with signs of a dose-dependent protective effect of CAG repeat length. The latter finding needs to be confirmed in even larger cohorts as these repeat numbers are relatively rare.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Lifetime risk of cancer in carriers of intermediate alleles in the HTT gene

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月16日

查看全文
  • Jimmy Sundblom,
  • Ingvar Bergdahl,
  • Eva-Lena Stattin,
  • Valter Niemelä

摘要

Previous studies have found a markedly reduced risk of cancer among Huntington’s disease (HD) patients with CAG ≥ 40, but data on cancer risk at shorter repeat numbers are lacking. The study includes 8149 subjects from Northern Sweden Health and Disease Study. Genotyping yielded a large number of intermediate allele carriers (IA, CAGn 27–35, (n = 497), normal alleles (CAGn 17–26,n = 6584), short alleles (CAG ≤ 16, n = 169) and 31 subjects with > 35 repeats, including reduced penetrance alleles (36–39; not guaranteed to suffer HD symptoms during a normal lifespan) and HD alleles > 39. Cancer diagnoses were retrieved from the Swedish Cancer Registry and the Hospital Discharge Registry and death certificates. We used Kaplan-Meier curves and Cox proportional hazard models to estimate the time to cancer, on strata of the population created by CAG repeat number intervals. Smoking status, BMI, as well as alcohol consumption were included in the models. 2735 participants (33.6%) had ≥ 1 cancer type. The Hazard-Ratio (HR) for IA carriers compared with normal alleles was similar, 0.97 CI 0.82–1.15). The reduced penetrance allele group (CAGn 36–39, n = 29) had HR of 0.54 CI 0.22–1.30 similar to what has been reported with a full penetrance allele. Intermediate allele carriers as a group did not have a reduced risk of cancer. It remains possible that reduced penetrance alleles confer lower risk of cancer, with signs of a dose-dependent protective effect of CAG repeat length. The latter finding needs to be confirmed in even larger cohorts as these repeat numbers are relatively rare.