Hemochromatosis risk genotype is not associated with colorectal cancer or age at its diagnosis.
Jarvik GP, Wang X, Fontanillas P, Kim E, Chanprasert S, Gordon AS, Bastarache L, Kowdley KV, Harrison T, Rosenthal EA, Stanaway IB, Bézieau S, Weinstein SJ, Newcomb PA, Casey G, Platz EA, Visvanathan K, Le Marchand L, Ulrich CM, Hardikar S, Li CI, van Duijnhoven FJB, Gsur A, Campbell PT, Moreno V, Vodička P, Brenner H, Chang-Claude J, Hoffmeister M, Slattery ML, Gunter MJ, Aglago EK, Castellví-Bel S, Kweon SS, Chan AT, Li L, Zheng W, Bishop DT, Giles GG, Rennert G, Offit K, Keku TO, Woods MO, Hampe J, Van Guelpen B, Gallinger SJ, de la Chapelle A, Hampel H, Berndt SI, Tangen CM, Lindblom A, Wolk A, Burnett-Hartman A, Wu AH, White E, 23andMe Research Team, Gruber SB, Jenkins MA, Mountain J, Peters U, Crosslin DR
Homozygotes for the higher penetrance hemochromatosis risk allele, HFE c.845G>A (p.Cys282Tyr, or C282Y), have been reported to be at a 2- to 3-fold increased risk for colorectal cancer (CRC). These results have been reported for small sample size studies with no information about age at diagnosis for CRC. An association with age at diagnosis might alter CRC screening recommendations. We analyzed two large European ancestry datasets to assess the association of HFE genotype with CRC risk and age at CRC diagnosis. The first dataset included 59,733 CRC or advanced adenoma cases and 72,351 controls from a CRC epidemiological study consortium. The second dataset included 13,564 self-reported CRC cases and 2,880,218 controls from the personal genetics company, 23andMe. No association of the common hereditary hemochromatosis (HH) risk genotype and CRC was found in either dataset. The odds ratios (ORs) for the association of CRC and HFE C282Y homozygosity were 1.08 (95% confidence interval [CI], 0.91-1.29; p = 0.4) and 1.01 (95% CI, 0.78-1.31, p = 0.9) in the two cohorts, respectively. Age at CRC diagnosis also did not differ by HFE C282Y/C282Y genotype in either dataset. These results indicate no increased CRC risk in individuals with HH genotypes and suggest that persons with HH risk genotypes can follow population screening recommendations for CRC.
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