Of these, 24,339 (854%) were wild-type, 3977 (133%) were C282Y

Of these, 24,339 (85.4%) were wild-type, 3977 (13.3%) were C282Y heterozygotes, and 193 (0.64%) were C282Y homozygotes. The expected numbers under Hardy-Weinberg equilibrium are 24,313 wild-type, 4029 heterozygous, and 167 homozygous (P = 0.03); thus, there was an excess of homozygotes and a deficit of heterozygotes. Genotyping

for H63D was successful for 3882 (98%) of the 3977 C282Y heterozygotes, of which Small Molecule Compound Library 690 (17.8%) were heterozygous and thus were heterozygous for both the C282Y and H63D variants. We excluded from further analysis the 95 participants for whom the H63D genotyping failed, because it was not known whether they were simple C282Y heterozygotes or compound heterozygotes. It was not possible to check for Hardy-Weinberg equilibrium because of the restriction of

H63D genotyping to C282Y heterozygotes. A summary of baseline characteristics for participants successfully genotyped is presented in Table 1. C282Y homozygotes had the lowest mean body mass index, which would mean that any confounding of the association would be toward the null. A higher proportion of male participants than female participants were C282Y homozygotes. Only minor differences were seen for other risk factors. Between initial attendance and December 31, 2007, 84 participants had left Australia and 3365 were confirmed dead. There were 620 participants diagnosed with colorectal cancer (mean age at diagnosis, 68.3; range, check details 42.0–83.3 years), 664 women diagnosed with breast cancer (mean age at diagnosis, 62.8; range, 41.3–82.0 years), 758 men diagnosed with prostate cancer (mean age at diagnosis, 67.6; range, 47.6–83.6 years), 3755 with

nonhematological cancers (mean age at diagnosis, 66.1; range, 41.3–84.4 years), and 4025 with any cancer (mean age at diagnosis, 66.1; range, 41.3–84.4 years). Table 2 presents the results of the Cox regression analysis of the association between the C282Y and H63D variants of the HFE gene and the risk of cancer. C282Y homozygotes had an increased risk of colorectal cancer compared with those with no C282Y variant (HR, 2.28; 95% confidence interval [CI], 1.22, 4.25). Similarly, female C282Y homozygotes had increased risk of breast cancer Ponatinib molecular weight compared with those with no C282Y variant (HR, 2.39; 95% CI, 1.24, 4.61). There was no evidence of increased risk of prostate cancer for male C282Y homozygotes (HR, 0.96; 95% CI, 0.43, 2.15), although the wide confidence interval does not preclude the possibility of an association of similar magnitude to those seen for breast and colorectal cancer. The HR for all other nonhematological cancers was 1·15 (95% CI, 0.73, 1.81). HRs for simple and compound heterozygotes were close to unity for each of the cancers in Table 2; the strongest association was for compound heterozygotes and risk of colorectal cancer (HR, 1.27; 95% CI, 0.8, 2.1). Exclusion of the first 2 years of follow-up made no material difference to any of the results (data not shown).

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