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Journal of the National Cancer Institute Advance Access published online on December 11, 2007

JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djm248
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© The Author 2007. Published by Oxford University Press.

ARTICLES

Cancer Incidence in Blood Transfusion Recipients

Henrik Hjalgrim, Gustaf Edgren, Klaus Rostgaard, Marie Reilly, Trung Nam Tran, Kjell Einar Titlestad, Agneta Shanwell, Casper Jersild, Johanna Adami, Agneta Wikman, Gloria Gridley, Louise Wideroff, Olof Nyrén, Mads Melbye

Affiliations of authors: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (HH, KR, MM); Karolinska Institutet, Stockholm, Sweden (GE, MR, TNT, JA, ON); Department of Epidemiology, Merck Research Laboratories, Philadelphia, PA (TNT); Department of Clinical Immunology, Odense University Hospital, Odense, Denmark (KET); Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden (AS, AW); Department of Clinical Immunology, Århus University Hospital, Århus, Denmark (CJ); Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden (JA); Divisions of Cancer Epidemiology and Genetics (GG) and Cancer Control and Population Sciences (LW), National Cancer Institute, Bethesda, MD

Correspondence to: Henrik Hjalgrim, MD, PhD, Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen South, Denmark (e-mail: hhj{at}ssi.dk).

Background: Blood transfusions may influence the recipients' cancer risks both through transmission of biologic agents and by modulation of the immune system. However, cancer occurrence in transfusion recipients remains poorly characterized.

Methods: We used computerized files from Scandinavian blood banks to identify a cohort of 888843 cancer-free recipients transfused after 1968. The recipients were followed from first registered transfusion until the date of death, emigration, cancer diagnosis, or December 31, 2002, whichever came first. Relative risks were expressed as ratios of the observed to the expected numbers of cancers, that is, standardized incidence ratios (SIRs), using incidence rates for the general Danish and Swedish populations as a reference. All statistical tests were two-sided.

Results: During 5652918 person-years of follow-up, 80990 cancers occurred in the transfusion recipients, corresponding to a SIR of 1.45 (95% confidence interval [CI] = 1.44 to 1.46). The SIR for cancer overall decreased from 5.36 (95% CI = 5.29 to 5.43) during the first 6 months after transfusion to 1.10 or less for follow-up periods more than 2 years after the transfusion. However, the standardized incidence ratios for cancers of the tongue, mouth, pharynx, esophagus, liver, and respiratory and urinary tracts and for squamous cell skin carcinoma remained elevated beyond 10 years after the transfusion.

Conclusions: The marked increase in cancer risk shortly after a blood transfusion may reflect the presence of undiagnosed occult cancers with symptoms that necessitated the blood transfusion. The continued increased risk of tobacco- and alcohol-related cancers suggests that lifestyle and other risk factors related to conditions prompting transfusion rather than transfusion-related exposures per se are important to the observed cancer occurrence in the recipients.



CONTEXT AND CAVEATS

Prior knowledge

Blood transfusions can expose recipients to transmissible biologic agents that are known or suspected to be associated with cancer occurrence and may also alter recipients' immune systems, thereby placing them at increased risks of some cancers.

Study design

A population-based study that used computerized blood bank and health data to examine cancer occurrence among a cohort of blood transfusion recipients in Sweden and Denmark.

Contribution

Among blood transfusion recipients, there was a marked increase in the relative risk of most cancers and cancer overall during the first 6 months after transfusion that decreased over time. Risks of cancers that share tobacco and alcohol use as risk factors were elevated for 10–20 years after the blood transfusion.

Implications

The marked increase in cancer risk shortly after blood transfusion may reflect the presence of undiagnosed cancers that prompted the transfusion. The continued excess occurrence of cancers associated with tobacco and alcohol use suggests that these and other risk factors that are related to the condition that prompted the transfusion contribute to the cancer pattern observed in these blood transfusion recipients.

Limitations

Multiple comparisons increased the risk of chance findings. Computerized registration of blood transfusion was implemented nonuniformly. Some recipients may have received a transfusion before computerized databases were introduced.

 
Manuscript received April 16, 2007; revised October 8, 2007; accepted November 5, 2007.


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