title: The leptin gene family and colorectal cancer: interaction with smoking behavior and family history of cancer.
abstract: BACKGROUND
  Pathologic condition associated with metabolic syndrome traits seems to increase the risk of colorectal cancer. One mechanism underlying this relationship may involve the growth-promoting effects of the circulation hormones associated with obesity and insulin resistance, such as leptin.
  
  
  RESULTS
  A two-stage case-control study was used to explore the role of polymorphisms of Leptin (LEP) and Leptin receptor (LEPR), either alone or in combination with environmental factors in colorectal carcinogenesis. In stage 1, 20 single nucleotide polymorphisms (SNPs) that tag common SNPs in these two genes were genotyped among 470 cases and 458 controls. In stage 2, another population with 314 cases and 355 controls were genotyped for the two most promising SNPs from stage 1. LEPR rs12037879 only presented modestly increased colorectal cancer risk, with odds ratios of 1.41 (95% confidence interval [CI] 1.13-1.76) and 1.74 (95%CI 1.08-2.81) for GA and AA genotype when compared with GG genotype in combined population. Smokers carrying LEPR rs12037879 A allele presented 1.67-fold (95%CI 1.39-fold to 2.01-fold) increased colorectal cancer risk when compared with non-smokers carrying GG genotype in combined analysis. Individuals with family history of cancer harboring LEPR rs12037879 A allele showed 1.52-fold (95%CI: 1.24-fold to 1.86-fold) increased colorectal cancer risk, compared with individuals without family history of cancer harboring GG genotype. Multifactor gene-environment interaction analysis revealed significant interactions among LEPR rs12037879, LEPR rs6690625, smoking status and family history of cancer, exhibiting a gradient of increased colorectal cancer risk along with the increasing number of risk factors (P = 9.82 × 10(-10)).
  
  
  CONCLUSIONS
  Our research supports that polymorphisms in LEPR may be associated with marginal increase in the risk for colorectal cancer. Moreover, this association could be strengthened by cigarette smoking and family history of cancer.
authors.affiliation: Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.forename: Sheng
authors.initials: S
authors.lastname: Wei
authors.forename: Hao
authors.initials: H
authors.lastname: Xiang
authors.forename: Jigui
authors.initials: J
authors.lastname: Chen
authors.forename: Duoshuang
authors.initials: D
authors.lastname: Xie
authors.forename: Jieyun
authors.initials: J
authors.lastname: Yin
authors.forename: Li
authors.initials: L
authors.lastname: Zou
authors.forename: Jingwen
authors.initials: J
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Shaofa
authors.initials: S
authors.lastname: Nie
mesh_terms: D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D020738:Leptin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D054411:Receptors, Leptin / Q000235:genetics; D012907:Smoking / Q000009:adverse effects*
chemical_list: D020738:Leptin; D054411:Receptors, Leptin