title: Estrogen and progesterone-related gene variants and colorectal cancer risk in women.
abstract: BACKGROUND
  Observational studies and randomized trials have suggested that estrogens and/or progesterone may lower the risk for colorectal cancer. Inherited variation in the sex-hormone genes may be one mechanism by which sex hormones affect colorectal cancer, although data are limited.
  
  
  METHODS
  We conducted a comprehensive evaluation of single nucleotide polymorphisms (SNPs) in genes encoding 3 hormone receptors (ESR1, ESR2, PGR) and 5 hormone synthesizers (CYP19A1 and CYP17A1, HSD17B1, HSD17B2, HSD17B4) among 427 women with incident colorectal cancer and 871 matched controls who were Caucasians of European ancestry from 93676 postmenopausal women enrolled in the Women's Health Initiative Observational cohort. A total of 242 haplotype-tagging and functional SNPs in the 8 genes were included for analysis. Unconditional logistic regression with adjustment for age and hysterectomy status was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
  
  
  RESULTS
  We observed a weak association between the CYP17A1 rs17724534 SNP and colorectal cancer risk (OR per risk allele (A) = 1.39, 95% CI = 1.09-1.78, corrected p-value = 0.07). In addition, a suggestive interaction between rs17724534 and rs10883782 in 2 discrete LD blocks of CYP17A1 was observed in relation to colorectal cancer (empirical p value = 0.04). Moreover, one haplotype block of CYP19A1 was associated with colorectal cancer (corrected global p value = 0.02), which likely reflected the association with the tagging SNP, rs1902584, in the block.
  
  
  CONCLUSIONS
  Our findings offer some support for a suggestive association of CYP17A1 and CYP19A1 variants with colorectal cancer risk.
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. jhlin@rics.bwh.harvard.edu
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Lin
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Cochrane
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: Shumin M
authors.initials: SM
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000728:Androgens / Q000378:metabolism; D001141:Aromatase / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D047628:Estrogen Receptor alpha / Q000235:genetics; D047629:Estrogen Receptor beta / Q000235:genetics; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000235:genetics; D011374:Progesterone / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
chemical_list: D000728:Androgens; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011980:Receptors, Progesterone; D011374:Progesterone; D006913:Hydroxysteroid Dehydrogenases; C035507:3(17)-hydroxysteroid dehydrogenase; D001141:Aromatase; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase