Genetics of risk factors for melanoma: An adult twin study of nevi and freckles
Genetics of risk factors for melanoma: An adult twin study of nevi and freckles
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DOI：
10.1093/jnci/92.6.457
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发表时间：
2000-03-15
影响因子：
10.3
通讯作者：
Spector, TD
中科院分区：
文献类型：
--
作者：
Bataille, V;Snieder, H;Spector, TD
背景：我们试图通过一项成人双胞胎研究来调查遗传和环境效应对黑色素瘤的已知危险因素-雀斑和雀斑表达的相对贡献，并确定年龄和阳光暴露是否影响雀斑的遗传性。设计和方法：对127对同卵双胞胎和323对异卵双胞胎进行了雀斑和雀斑总数的测定。采用方差分析计算组内相关系数。模型拟合分析量化了雀斑和雀斑计数的遗传和环境因素。结果：在单卵配对中，雀斑总数的组内相关系数为83，而在双卵配对中为51。定量遗传分析表明，遗传因素对nevi表达的贡献因年龄而异。在小于45岁的双生子中，雀斑总数的加性遗传方差为36%(95%可信区间[CI]=0.8%-63%)，其余变异的38%(95%可信区间=14%-61%)和26%(95%可信区间=16%-42%)分别归因于共同环境和独特环境效应。在45岁或以上的双胞胎中，常见的环境对雀斑总数的影响变得可以忽略不计，加性遗传方差增加到84%(95%CI=77%-88%)，身体部位也被发现影响了雀斑计数的遗传力估计，在阳光暴晒和阳光照射的地点之间存在统计学上的显著差异。在同卵双胞胎中，雀斑总数的多配对相关性(即超过两个类别的双胞胎内的易感性相关性)为0.91，而在异卵双胞胎中为0.54。加性遗传效应可解释91%(95%CI=86%-94%)的雀斑数量变异。结论：遗传因素对色素痣总数方差的贡献随年龄增长而增加，日光照射似乎会影响雀斑的表达，本研究结果强调了在寻找新的黑色素瘤基因时，有必要考虑雀斑计数的年龄和位置，以进行未来的遗传连锁或关联研究。
Background: We sought by use of an adult twin study to investigate the relative contribution of genetic and environmental effects on the expression of nevi and freckles, which are known risk factors for melanoma, and to determine if age and sun exposure influence the heritability of nevi, Design and Methods: Total nevus and freckle counts were conducted on 127 monozygotic twin pairs and 323 dizygotic twin pairs. Intraclass correlations were calculated by use of analysis of variance. Model-fitting analyses were performed to quantify the genetic and environmental components of the variance for nevus and freckle counts.Results: The intraclass correlation for total nevus counts was 83 in monozygotic pairs compared with 51 in dizygotic pairs. Quantitative genetic analyses showed that the contribution of genetic factors on nevi expression varied according to age. For twins less than 45 years old, the additive genetic variance on total nevus count was 36% (95% confidence interval [Cl] = 0.8%-63%), with 38% (95% CI = 14%-61%) and 26% (95% CI = 16%-42%) of the remaining variance attributed to common environment and unique environmental effects, respectively. In twins aged 45 years or older, common environmental effects on total nevus count became negligible, with the additive genetic variance increasing to 84% (95% CI = 77%-88%), Body site was also found to affect the heritability estimates for nevus counts, with a statistically significant difference between sun-exposed and sun-protected sites. The polychoric correlation (i.e., the correlation in liability within twins for more than two categories) for total freckle counts was .91 in monozygotic twin pairs compared with .54 in dizygotic twin pairs. Additive genetic effects explained 91% (95% CI = 86%-94%) of the variance in freckle counts. Conclusion: The contribution of genetic factors on the variance for total nevus counts increased with age, and sun exposure appears to influence the expression of nevi, The results of this study highlight the need to take into account the age and site of nevus counts for future genetic linkage or association studies in the search for new melanoma genes.