Elmberg Maria, Hultcrantz Rolf, Ekbom Anders, Brandt Lena, Olsson Sigvard, Olsson Rolf, Lindgren Stefan, Lööf Lars, Stål Per, Wallerstedt Sven, Almer Sven, Sandberg-Gertzén Hanna, Askling Johan
Department of Gastroenterology and Hepatology, Karolinska Hospital, Stockholm, Sweden.
Gastroenterology. 2003 Dec;125(6):1733-41. doi: 10.1053/j.gastro.2003.09.035.
BACKGROUND & AIMS: Iron overload may be carcinogenic. Patients with hereditary hemochromatosis (HH) are reportedly at a 20-200-fold risk of intrahepatic cancer, but the reported risks for nonhepatobiliary cancers are conflicting. The risk of cancer in heterozygous individuals (estimated allele frequency, 1/10 to 1/20) is unknown. This study aimed to better assess these risks.
We performed a population-based cohort study of 1847 Swedish patients with HH and 5973 of their first-degree relatives using nationwide, population-based health and census registers. We used standardized incidence ratios (SIRs) as relative risk.
With 62 liver cancers and 128 nonhepatobiliary cancers, patients with HH were at a 20-fold risk of liver cancer (SIR, 21; 95% confidence interval [CI], 16-22) but an almost unaltered risk of all other cancers (SIR, 1.2; 95% CI, 1.0-1.4), including nonelevated risks for several gastrointestinal tract cancers. At 10 years of follow-up, the absolute risk of liver cancer was 6% among men and 1.5% among women. With 21 liver cancers and 508 nonhepatobiliary cancers, first-degree relatives were at an unaltered risk of extrahepatic cancer (SIR, 1.0; 95% CI, 0.9-1.1, including unelevated risks for gastrointestinal cancers) but at a modest and historic increased risk of hepatobiliary cancer (SIR, 1.5; 95% CI, 1.0-2.4), the histopathologic spectrum of which differed from the patients.
Patients (particularly men) with HH are at increased risk for hepatocellular cancer, although the magnitude of the risk is lower than previous estimates. Overall cancer risk in first-degree relatives does not seem to be increased.
铁过载可能具有致癌性。据报道，遗传性血色素沉着症（HH）患者患肝癌的风险是常人的20至200倍，但关于非肝胆系统癌症的风险报道存在矛盾。杂合子个体（估计等位基因频率为1/10至1/20）患癌风险未知。本研究旨在更好地评估这些风险。
我们利用全国性的基于人群的健康和人口普查登记册，对1847名瑞典HH患者及其5973名一级亲属进行了一项基于人群的队列研究。我们使用标准化发病率比（SIR）作为相对风险。
HH患者中有62例肝癌和128例非肝胆系统癌症，患肝癌的风险是常人的20倍（SIR为21；95%置信区间[CI]为16 - 22），但所有其他癌症的风险几乎未改变（SIR为1.2；95%CI为1.0 - 1.4），包括几种胃肠道癌症的风险未升高。随访10年时，男性患肝癌的绝对风险为6%，女性为1.5%。一级亲属中有21例肝癌和508例非肝胆系统癌症，肝外癌症风险未改变（SIR为1.0；95%CI为0.9 - 1.1，包括胃肠道癌症风险未升高），但肝胆系统癌症风险有适度且历史性的增加（SIR为1.5；95%CI为1.0 - 2.4），其组织病理学谱与患者不同。
HH患者（尤其是男性）患肝细胞癌的风险增加，尽管风险程度低于先前估计。一级亲属的总体癌症风险似乎未增加。
