Genetic analyses supporting colorectal, gastric, and prostate cancer syndromes

Genes Chromosomes Cancer. 2019 Nov;58(11):775-782. doi: 10.1002/gcc.22786. Epub 2019 Aug 7.

Abstract

Colorectal cancer (CRC), prostate cancer (PrC), and gastric cancer (GC) are common worldwide, and the incidence is to a certain extent dependent on genetics. We have recently shown that in families with more than one case of CRC, the risk of other malignancies is increased. We therefore suggested the presence of not yet described CRC syndromes. In this study, we have searched for genetic susceptibility loci for potential cancer syndromes involving CRC combined with PrC and/or GC. We have performed SNP (single-nucleotide polymorphism)-based linkage analyses in 45 families with CRC, PrC, and GC. In the regions with suggested linkage, we performed exome and association haplotype analyses. Five loci generated a high logarithm of odds (HLOD) score >2, suggestive of linkage, in chromosome bands 1q31-32, 1q24-25, 6q25-26, 18p11-q11, and Xp11. Exome analysis detected no potential pathogenic sequence variants. The haplotype association study showed that one of the top five haplotypes with the lowest P value in the chromosome band 6q25 interestingly was found in the family which contributed the most to the increased HLOD at that locus. This study supports a suggested hereditary cancer syndrome involving CRC and PrC and indicates a location at 6q25. The impact of this locus needs to be confirmed in additional studies.

Keywords: colon; gastric cancer syndromes; prostate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms / genetics
  • Family
  • Female
  • Genetic Linkage / genetics
  • Genetic Loci
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing / methods
  • Genome-Wide Association Study
  • Haplotypes / genetics
  • Humans
  • Male
  • Neoplastic Syndromes, Hereditary / genetics*
  • Pedigree
  • Polymorphism, Single Nucleotide / genetics
  • Prostatic Neoplasms / genetics
  • Risk Factors
  • Stomach Neoplasms / genetics
  • Whole Exome Sequencing / methods