title: Associations between cigarette smoking, hormone therapy, and folate intake with incident colorectal cancer by TP53 protein expression level in a population-based cohort of older women.
abstract: Cigarette smoking (CS), hormone therapy (HT), and folate intake (FI) are each thought to influence colorectal cancer risk, but the underlying molecular mechanisms remain incompletely defined. The TP53 (p53) protein, encoded by the TP53 tumor-suppressor gene that is commonly mutated in colorectal cancer, can be readily assessed to differentiate biologically distinct colorectal cancer subtypes. In this prospective cohort study, we examined CS-, HT-, and FI-associated colorectal cancer risks by TP53 protein expression level among Iowa Women's Health Study (IWHS) participants. The IWHS recruited 41,836 randomly selected Iowa women, ages 55 to 69 years, with a valid driver's license at study entry in 1986. Self-reported exposure variables were assessed at baseline. Incident colorectal cancer cases were ascertained by annual linkage with the Iowa Cancer Registry. Archived, paraffin-embedded tissue specimens were collected and evaluated for TP53 protein expression by immunohistochemistry. Multivariate Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI) for associations between CS, HT, or FI and TP53-defined colorectal cancer subtypes. Informative environmental exposure and protein expression data were available for 492 incident colorectal cancer cases: 222 (45.1%) TP53 negative, 72 (14.6%) TP53 low, and 198 (40.2%) TP53 high. Longer duration (>5 years) of HT was inversely associated with TP53 high colorectal cancers (RR, 0.50; 95% CI, 0.27-0.94). No other statistically significant associations were observed. These data support possible heterogeneous effects from HT on TP53-related pathways of colorectal carcinogenesis in older women.
authors.affiliation: Authors' Affiliations: Departments of Laboratory Medicine and Pathology and Health Sciences Research; Division of Epidemiology; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester; Department of Epidemiology, University of Minnesota, Minneapolis, Minnesota; Department of Medicine (Gastroenterology), Huntsman Cancer Institute and University of Utah, Salt Lake City, Utah; Department of Epidemiology, University of Iowa, Iowa City, Iowa; Department of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California; and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Lori S
authors.initials: LS
authors.lastname: Tillmans
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Alice H
authors.initials: AH
authors.lastname: Wang
authors.forename: N
authors.initials: N
authors.lastname: Jewel Samadder
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Anderson
authors.forename: Amy J
authors.initials: AJ
authors.lastname: French
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Harnack
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Smyrk
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Limburg
mesh_terms: D000367:Age Factors; D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000706:statistics & numerical data*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D007484:Iowa / Q000453:epidemiology; D008875:Middle Aged; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D005492:Folic Acid