Epidemiology and Public Health Group, University of Exeter Medical School, Exeter, United Kingdom.
Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, Connecticut.
Cancer Epidemiol Biomarkers Prev. 2022 Sep 2;31(9):1780-1787. doi: 10.1158/1055-9965.EPI-22-0284.
In European ancestry populations, iron overload disorder hereditary hemochromatosis 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 nonmelanoma and liver cancer) and common incident cancers [bladder, blood (with subanalyses of leukemia and lymphoma), bone, brain, breast, colorectal, kidney, lung, melanoma, esophageal, ovarian, pancreatic, prostate and stomach] in those with p.C282Y and p.H63D genotypes, compared with participants without HFE mutations.
Male p.C282Y homozygotes (n = 2,890, 12.1% with baseline diagnosed hereditary hemochromatosis) had increased incidence of prostate cancer [6.8% vs. 5.4% without mutations; HR = 1.32; 95% confidence interval (CI), 1.07-1.63; P = 0.01; Bonferroni adjusted P = 0.17] during follow-up. In life table estimates from ages 40 to 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 (nonliver) 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.
在欧洲血统人群中，铁过载疾病遗传性血色素沉着症主要由 HFE p.C282Y 和 p.H63D 突变引起。男性 p.C282Y 纯合子的肝恶性肿瘤发病率明显增加，但男性和女性纯合子患其他癌症的风险尚不清楚。
英国生物库 451143 名欧洲血统参与者（年龄 40-70 岁；54.3%为女性）通过住院和国家癌症登记处进行随访（平均随访 11.6 年）。我们估计了那些具有 p.C282Y 和 p.H63D 基因型的人（与没有 HFE 突变的参与者相比）患任何（非黑色素瘤和肝癌）和常见（膀胱癌、血液（白血病和淋巴瘤的亚分析）、骨癌、脑癌、乳腺癌、结直肠癌、肾癌、肺癌、黑色素瘤、食管癌、卵巢癌、胰腺癌、前列腺癌和胃癌）癌症的风险。
男性 p.C282Y 纯合子（n = 2890 人，基线诊断遗传性血色素沉着症 12.1%）在随访期间前列腺癌的发病率增加（6.8% vs. 无突变者 5.4%；HR = 1.32；95%置信区间（CI），1.07-1.63；P = 0.01；Bonferroni 调整后 P = 0.17）。在 40-75 岁的寿命表估计中，预计 14.4%的男性 p.C282Y 纯合子将患前列腺癌（而无突变者为 10.7%，多余 3.8%；95%CI，1.3-6.8）。在男性或女性 p.C282Y 纯合子中，或在任何其他 p.C282Y/p.H63D 基因型的两性中，未发现其他研究癌症的风险增加。
在一个大型社区 p.C282Y 纯合子男性样本中，有迹象表明前列腺癌发病率增加，但没有其他（非肝脏）研究癌症的过量证据。
需要在其他大型社区基因分型队列中复制结果，以确认是否需要对 p.C282Y 纯合子男性进行前列腺癌的临床监测。
