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.
Highlights
Genomic instability is an important molecular event in the development of colorectal cancer (CRC) [1], encompassing chromosomal instability, microsatellite instability and aberrant DNA methylation.Chromosomal instability is the most common type of genomic instability and is an early event in colorectal carcinogenesis [2] causing chromosomal copy number aberrations (CNA)
Tumors were from different colonic sites with 28 tumors (24.2%) being right-sided, 47 tumors (40.5%) being left-sided, 23 (19.8%) rectal, and 18 (15.5%) of unknown site
Sex hormonal influences and the protective effect of estrogen in women have long been proposed as a factor in this gender bias in the incidence and behavior of CRC [30,36], as opposed to testosterone, which is generally thought to contribute to increased aggressiveness of cancer in males [37,38]
Summary
Genomic instability is an important molecular event in the development of colorectal cancer (CRC) [1], encompassing chromosomal instability, microsatellite instability and aberrant DNA methylation. Chromosomal instability is the most common type of genomic instability and is an early event in colorectal carcinogenesis [2] causing chromosomal copy number aberrations (CNA). CNAs in CRC have been extensively studied using cytogenetic techniques and comparative genomic hybridization (CGH) [3,4,5,6,7,8,9]. Despite recent advances in CRC genomics, gender-specific CNAs have only been sporadically documented by CRC genomic studies. Studying gender-related genomics can help optimize therapeutic strategies in the era of personalized medicine
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