TY - JOUR
T1 - Associations between environmental exposures and incident colorectal cancer by ESR2 protein expression level in a population-based cohort of older women
AU - Tillmans, Lori S.
AU - Vierkant, Robert A.
AU - Wang, Alice H.
AU - Samadder, Niloy Jewel
AU - Lynch, Charles F.
AU - Anderson, Kristin E.
AU - French, Amy J.
AU - Haile, Robert W.
AU - Harnack, Lisa J.
AU - Potter, John D.
AU - Slager, Susan L.
AU - Smyrk, Thomas C.
AU - Thibodeau, Stephen N.
AU - Cerhan, James R.
AU - Limburg, Paul J.
N1 - Publisher Copyright:
© 2015 AACR.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Background: Cigarette smoking (smoking), hormone therapy (MHT), and folate intake (folate) are each thought to influence colorectal cancer risk, but the underlying molecular mechanisms remain incompletely defined. Expression of estrogen receptor β (ESR2) has been associated with colorectal cancer stage and survival. Methods: In this prospective cohort study, we examined smoking, MHT, and folate-associated colorectal cancer risks by ESR2 protein expression level among participants in the Iowa Women's Health Study (IWHS). Self-reported exposure variables were assessed at baseline. Archived, paraffin-embedded colorectal cancer tissue specimens were collected and evaluated for ESR2 protein expression by IHC. Multivariate Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI) for associations between smoking, MHT, or folate and ESR2-defined colorectal cancer subtypes. Results: Informative environmental exposure and protein expression data were available for 491 incident colorectal cancer cases. Positive associations between ESR2-low and-high tumors and several smoking-related variables were noted, most prominently with average number of cigarettes per day (RR, 4.24; 95% CI, 1.81-9.91 for ESR2-low and RR, 2.15; 95% CI, 1.05-4.41 for ESR2-high for ≥40 cigarettes compared with nonsmokers). For MHT, a statistically significant association with ESR2-low tumors was observed with longer duration of exposure (RR, 0.54; 95% CI, 0.26-1.13 for >5 years compared with never use). No associations were found for folate. Conclusions: In this study, smoking and MHT were associated with ESR2 expression patterns. Impact: These data support possible heterogeneous effects from smoking and MHT on ERb-related pathways of colorectal carcinogenesis in older women. Cancer Epidemiol Biomarkers Prev; 24(4); 713-9.
AB - Background: Cigarette smoking (smoking), hormone therapy (MHT), and folate intake (folate) are each thought to influence colorectal cancer risk, but the underlying molecular mechanisms remain incompletely defined. Expression of estrogen receptor β (ESR2) has been associated with colorectal cancer stage and survival. Methods: In this prospective cohort study, we examined smoking, MHT, and folate-associated colorectal cancer risks by ESR2 protein expression level among participants in the Iowa Women's Health Study (IWHS). Self-reported exposure variables were assessed at baseline. Archived, paraffin-embedded colorectal cancer tissue specimens were collected and evaluated for ESR2 protein expression by IHC. Multivariate Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI) for associations between smoking, MHT, or folate and ESR2-defined colorectal cancer subtypes. Results: Informative environmental exposure and protein expression data were available for 491 incident colorectal cancer cases. Positive associations between ESR2-low and-high tumors and several smoking-related variables were noted, most prominently with average number of cigarettes per day (RR, 4.24; 95% CI, 1.81-9.91 for ESR2-low and RR, 2.15; 95% CI, 1.05-4.41 for ESR2-high for ≥40 cigarettes compared with nonsmokers). For MHT, a statistically significant association with ESR2-low tumors was observed with longer duration of exposure (RR, 0.54; 95% CI, 0.26-1.13 for >5 years compared with never use). No associations were found for folate. Conclusions: In this study, smoking and MHT were associated with ESR2 expression patterns. Impact: These data support possible heterogeneous effects from smoking and MHT on ERb-related pathways of colorectal carcinogenesis in older women. Cancer Epidemiol Biomarkers Prev; 24(4); 713-9.
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U2 - 10.1158/1055-9965.EPI-14-0756
DO - 10.1158/1055-9965.EPI-14-0756
M3 - Article
C2 - 25650184
AN - SCOPUS:84927938690
SN - 1055-9965
VL - 24
SP - 713
EP - 719
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 4
ER -