Risk of cervical cancer associated with allergies and polymorphisms in genes in the chromosome 5 cytokine cluster.
BACKGROUND
Human papillomavirus is the acknowledged cause of cervical cancer. We hypothesized that allergies, characterized by hyperimmune reaction to common allergens and which have been associated with various cancers, may be related to cervical cancer, and that genetic variation in cytokine genes related to allergies might impact cervical cancer risk.


METHODS
We investigated the risk of invasive squamous cell cervical cancer (SCC) associated with self-reported allergies and with variation in allergy-related cytokine genes using data from a case-control study (561 cases, 1,258 controls) conducted in Washington State. Logistic regression models yielded odds ratios (OR) and 95% CI.


RESULTS
Pollen allergy, the most commonly reported allergy, was associated with reduced SCC risk (OR: 0.6; 95% CI: 0.5-0.8). Of 60 tagging single-nucleotide polymorphisms covering eight genes (CSF2, IL3, IL4, IL13, CSF2RB, IL4R, IL13RA1, IL13RA2), several were related to pollen allergies among controls: IL4R rs3024647 (dominant OR: 1.5; 95% CI: 1.0-2.3; P = 0.04), CSF2RB rs16997517 (dominant OR: 2.2; 95% CI: 1.0-4.7; P = 0.04), and IL13 rs1800925 (per-allele OR: 1.7; 95% CI: 1.3-2.4; P = 0.0007). Two variants were inversely associated with SCC risk: IL4R rs3024656 (per-allele OR: 0.8; 95% CI: 0.6-1.0; P = 0.03) and CSF2RB rs16997517 (dominant OR: 0.4; 95% CI: 0.2-0.9; P = 0.04).


CONCLUSIONS
Pollen allergies were related to reduced SCC risk. CSF2RB rs16997517 was directly related to pollen allergies in controls and to reduced SCC risk.


CONCLUSIONS
If other studies confirm these results, the mechanism behind allergy-associated immune response associated with SCC risk may be worth exploring in the context of therapeutic or prophylactic vaccines.
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, PO Box 19024, Seattle, WA 98109, USA. lgjohnso@fhcrc.org
Lisa G
LG
Johnson
Stephen M
SM
Schwartz
Mari
M
Malkki
Qin
Q
Du
Effie W
EW
Petersdorf
Denise A
DA
Galloway
Margaret M
MM
Madeleine
D000293:Adolescent; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D016022:Case-Control Studies; D002895:Chromosomes, Human, Pair 5; D016207:Cytokines / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D055815:Young Adult
D016207:Cytokines