title: The risk of new-onset cancer associated with HFE C282Y and H63D mutations: evidence from 87,028 participants.
abstract: To investigate the association between mutation of HFE (the principal pathogenic gene in hereditary haemochromatosis) and risk of cancer, we conducted a meta-analysis of all available case-control or cohort studies relating to two missense mutations, C282Y and H63D mutations. Eligible studies were identified by searching databases including PubMed, Embase and the ISI Web of Knowledge. Overall and subgroup analyses were performed and odds ratios (ORs) combined with 95% confidence intervals (CIs) were applied to evaluate the association between C282Y mutation, H63D mutation and cancer risk. Sensitivity and cumulative analyses were used to evaluate the stability of the results. A total of 36 eligible studies were included, comprising 13,680 cases and 73,348 controls. C282Y was significantly associated with elevated cancer risk in a recessive genetic model (OR: 1.991, 95% CI: 1.448-2.737). On subgroup analysis stratified by cancer type, statistically significantly increased cancer risks were found for breast cancer, colorectal cancer and hepatocellular carcinoma in a recessive model. When stratified by territory, a significantly increased risk of cancer was found in Oceanic populations in a recessive model and in Asian populations in an allele model and dominant model. H63D mutation did not significantly increase overall cancer risk in any genetic model. However, when, stratified by territory, an increased cancer risk was found in the Asian population in an allele and dominant. C282Y but not H63D mutation was related to elevated cancer risk. Further large-scale studies considering gene-environment interactions and functional research should be conducted to further investigate this association.
authors.affiliation: Department of Pathology, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Yang-Fan
authors.initials: YF
authors.lastname: Lv
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Rui-Xi
authors.initials: RX
authors.lastname: Hua
authors.affiliation: Department of Pathology, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Guang-Ning
authors.initials: GN
authors.lastname: Yan
authors.affiliation: Department of Pathology, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Meng
authors.affiliation: Department of Endocrinology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Liao
authors.affiliation: Department of Pathology, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Qiao-Nan
authors.initials: QN
authors.lastname: Guo
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D000071020:Hemochromatosis Protein / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017594:Publication Bias; D012307:Risk Factors
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein
keywords: C282Y; H63D; HFE; cancer; hereditary haemochromatosis; meta-analysis; mutation