Familial Risk and Heritability of Colorectal Cancer in the Nordic Twin Study of Cancer.
Familial Risk and Heritability of Colorectal Cancer in the Nordic Twin Study of Cancer.
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DOI：
10.1016/j.cgh.2016.12.041
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Hjelmborg JB
中科院分区：
文献类型：
--
作者：
Graff RE;Möller S;Passarelli MN;Witte JS;Skytthe A;Christensen K;Tan Q;Adami HO;Czene K;Harris JR;Pukkala E;Kaprio J;Giovannucci EL;Mucci LA;Hjelmborg JB
我们分析了来自双胞胎的数据，以确定遗传因素与环境因素在多大程度上可归因于结直肠癌的家族风险。我们还研究了结肠癌和直肠癌的遗传性是否不同，给出了不同病因的证据。我们的数据集包括来自北欧双胞胎癌症研究的39，990对同卵双胞胎和61，443对同性双卵双胞胎。我们比较了每种癌症的风险在双胞胎的受影响的共同双胞胎相对于队列风险（家族风险比; FRR）。然后，我们估计了可能归因于遗传因素（遗传力）的风险变化比例。从1943年到2010年，1861人被诊断患有结肠癌，1268人患有直肠癌。受影响的同卵双胞胎的单卵双胞胎相对于队列风险的结直肠癌FRR为3.1（95%CI，2.4-3.8）。受影响双胞胎的异卵双胞胎的结直肠癌FRR为2.2（95% CI，1.7-2.7）。我们估计，40%（95%CI，33%-48%）的结直肠癌风险变化可归因于遗传因素;独特的环境仅占剩余的责任。对于结肠癌，单卵双胞胎的FRR为3.3（95% CI，2.1-4.5），双卵双胞胎为2.6（95% CI，1.7-3.5）。对于直肠癌，单卵双胞胎的可比估计值为3.3（95% CI，1.5-5.1），双卵双胞胎为2.6（95% CI，1.2-4.0）。结肠癌和直肠癌的遗传率估计为16%（95% CI，0-46%）和15%（95% CI，0-50%），共同环境估计值为15%（95% CI，0-38%）和11%（95% CI，0-38%），独特环境估计值分别为68%（95% CI，57%-79%）和75%（95% CI，61%-88%）。个体间的遗传差异可以解释40%的结直肠癌易感性的变化;结肠癌和直肠癌的风险可能比结直肠癌风险的遗传成分少。患有结肠癌或直肠癌的同胞，特别是同卵双胞胎，应考虑进行个性化筛查。
We analyzed data from twins to determine how much the familial risk of colorectal cancer can be attributed to genetic factors vs environment. We also examined whether heritability is distinct for colon vs rectal cancer, given evidence of distinct etiologies. Our data set included 39,990 monozygotic and 61,443 same-sex dizygotic twins from the Nordic Twin Study of Cancer. We compared each cancer’s risk in twins of affected co-twins relative to the cohort risk (familial risk ratio; FRR). We then estimated the proportion of variation in risk that could be attributed to genetic factors (heritability). From earliest registration in 1943 through 2010, 1861 individuals were diagnosed with colon cancer and 1268 with rectal cancer. Monozygotic twins of affected co-twins had an FRR for colorectal cancer of 3.1 (95% CI, 2.4–3.8) relative to the cohort risk. Dizygotic twins of affected co-twins had an FRR for colorectal cancer of 2.2 (95% CI, 1.7–2.7). We estimated that 40% (95% CI, 33%–48%) of the variation in colorectal cancer risk could be attributed to genetic factors; unique environment only accounted for the remaining liability. For colon cancer, the FRR was 3.3 (95% CI, 2.1–4.5) for monozygotic twins and 2.6 (95% CI, 1.7–3.5) for dizygotic twins. For rectal cancer, comparable estimates were 3.3 (95% CI, 1.5–5.1) for monozygotic twins and 2.6 (95% CI, 1.2–4.0) for dizygotic twins. Heritability estimates for colon and rectal cancer were 16% (95% CI, 0–46%) and 15% (95% CI, 0–50%), common environment estimates were 15% (95% CI, 0–38%) and 11% (95% CI, 0–38%), and unique environment estimates were 68% (95% CI, 57%–79%) and 75% (95% CI, 61%–88%), respectively. Inter-individual genetic differences could account for 40% of the variation in susceptibility to colorectal cancer; risk for colon and rectal cancers might have less of a genetic component than risk for colorectal cancer. Siblings, and particularly monozygotic co-twins, of individuals with colon or rectal cancer should consider personalized screening.
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