Hereditary Hemochromatosis Variant Associations with Incident Nonliver Malignancies: 11-Year Follow-up in UK Biobank.
Hereditary Hemochromatosis Variant Associations with Incident Nonliver Malignancies: 11-Year Follow-up in UK Biobank.
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DOI：
10.1158/1055-9965.epi-22-0284
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发表时间：
2022-09-02
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在欧洲血统人群中，铁超负荷疾病遗传性血色病（HH）主要由HFE p.C282Y和p.H63D突变引起。男性p.C282Y纯合子的肝癌发病率明显增加，但男性和女性纯合子的其他癌症的风险尚不清楚。通过入院和国家癌症登记处对451，143名英国生物银行欧洲血统参与者（年龄40-70岁; 54.3%女性）进行了随访（平均11.6年）。我们估计了p.C282Y和p.H63D基因型患者与无HFE突变的受试者相比发生任何偶发癌症（非黑色素瘤和肝癌除外）和常见偶发癌症（膀胱、血液[白血病和淋巴瘤的亚组分析]、骨、脑、乳腺、结直肠、肾、肺、黑色素瘤、食管、卵巢、胰腺、前列腺和胃）的风险。随访期间，男性p.C282Y纯合子（n= 2，890，12.1%基线诊断为HH）的前列腺癌发生率增加（6.8% vs 5.4%无突变，HR=1.32，95% CI=1.07-1.63，p=0.01，Bonferroni校正的p值=0.17）。在40-75岁的寿命表估计中，14.4%的男性p.C282Y纯合子预计会患前列腺癌（而没有突变的为10.7%，超过3.8%，95% CI = 1.3-6.8）。在男性或女性p.C282Y纯合子或任何其他p.C282Y/p.H63D基因型组中，未发现其他研究癌症的风险增加。在男性p.C282Y纯合子的大型社区样本中，有提示性证据表明前列腺癌发病率增加，没有证据表明其他研究（非肝癌）癌症过多。需要在其他大型社区基因分型队列中复制结果，以确认是否有必要对p.C282Y纯合子男性进行前列腺癌临床监测。
In European ancestry populations, iron overload disorder Hereditary Hemochromatosis (HH) is predominantly caused by HFE p.C282Y and p.H63D mutations. Male p.C282Y homozygotes have markedly increased hepatic malignancy incidence but risks for other cancers in male and female homozygotes are unclear. 451,143 UK Biobank European ancestry participants (aged 40-70 years; 54.3% female) were followed (mean 11.6 years) via hospital admissions and national cancer registries. We estimated risks of any incident cancer (other than non-melanoma and liver cancer) and common incident cancers (bladder, blood [with sub-analyses of leukemia and lymphoma], bone, brain, breast, colorectal, kidney, lung, melanoma, oesophageal, ovarian, pancreatic, prostate and stomach) in those with p.C282Y and p.H63D genotypes, compared to participants without HFE mutations. Male p.C282Y homozygotes (n=2,890, 12.1% with baseline diagnosed HH) had increased incidence of prostate cancer (6.8% versus 5.4% without mutations, HR=1.32, 95% CI=1.07-1.63, p=0.01, Bonferroni adjusted p-value=0.17) during follow-up. In lifetable estimates from ages 40-75 years, 14.4% of male p.C282Y homozygotes are projected to develop prostate cancer (versus 10.7% without mutations, excess 3.8%, 95% CI = 1.3-6.8). No increases in risks were found for other studied cancers in male or female p.C282Y homozygotes, or in any other p.C282Y/p.H63D genotype groups of either sex. In a large community sample of male p.C282Y homozygotes, there is suggestive evidence of increased prostate cancer incidence, with no evidence of excess of other studied (non-liver) cancers. Replication of results in other large community genotyped cohorts are needed to confirm if clinical monitoring for prostate cancer is necessary in p.C282Y homozygous males.