title: Gender-associated genomic differences in colorectal cancer: clinical insight from feminization of male cancer cells.
abstract: Gender-related differences in colorectal cancer (CRC) are not fully understood. Recent studies have shown that CRC arising in females are significantly associated with CpG island methylator phenotype (CIMP-high). Using array comparative genomic hybridization, we analyzed a cohort of 116 CRCs (57 males, 59 females) for chromosomal copy number aberrations (CNA) and found that CRC in females had significantly higher numbers of gains involving chromosome arms 1q21.2-q21.3, 4q13.2, 6p21.1 and 16p11.2 and copy number losses of chromosome arm 11q25 compared to males. Interestingly, a subset of male CRCs (46%) exhibited a "feminization" phenomenon in the form of gains of X chromosomes (or an arm of X) and/or losses of the Y chromosome. Feminization of cancer cells was significantly associated with microsatellite-stable CRCs (p-value 0.003) and wild-type BRAF gene status (p-value 0.009). No significant association with other clinicopathological parameters was identified including disease-free survival. In summary, our data show that some CNAs in CRC may be gender specific and that male cancers characterized by feminization may constitute a specific subset of CRCs that warrants further investigation.
authors.affiliation: Department of Pathology, Faculty of Medicine, Health Sciences Center, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. rolapath@hotmail.com.
authors.forename: Rola H
authors.initials: RH
authors.lastname: Ali
authors.affiliation: Kuwait Medical Genetics Center, Ministry of Health, Safat 13001, Kuwait. mj_marafie@yahoo.com.
authors.forename: Makia J
authors.initials: MJ
authors.lastname: Marafie
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Health Sciences Center, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. milad.bitar@gmail.com.
authors.forename: Milad S
authors.initials: MS
authors.lastname: Bitar
authors.affiliation: Department of Forensic Evidence, Ministry of Interior, P.O. Box 12500, Shamiya 71655, Kuwait. fahad77@hotmail.com.
authors.forename: Fahad
authors.initials: F
authors.lastname: Al-Dousari
authors.affiliation: Department of Forensic Evidence, Ministry of Interior, P.O. Box 12500, Shamiya 71655, Kuwait. sismaeel@yahoo.com.
authors.forename: Samar
authors.initials: S
authors.lastname: Ismael
authors.affiliation: Department of Pathology, Faculty of Medicine, Health Sciences Center, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. hus4in@live.com.
authors.forename: Hussain
authors.initials: H
authors.lastname: Bin Haider
authors.affiliation: Department of Pathology, Faculty of Medicine, Health Sciences Center, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. waleed_mls@hotmail.com.
authors.forename: Waleed
authors.initials: W
authors.lastname: Al-Ali
authors.affiliation: Department of Pathology, Faculty of Medicine, Health Sciences Center, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. sindhujacob@hsc.edu.kw.
authors.forename: Sindhu P
authors.initials: SP
authors.lastname: Jacob
authors.affiliation: Department of Pathology, Faculty of Medicine, Health Sciences Center, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. fahd@al-mulla.org.
authors.forename: Fahd
authors.initials: F
authors.lastname: Al-Mulla
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D003710:Demography; D018572:Disease-Free Survival; D005260:Female; D005262:Feminization; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012737:Sex Factors
chemical_list: D048493:Proto-Oncogene Proteins B-raf