TY - JOUR
T1 - Postmenopausal hormone therapy and colorectal cancer risk in relation to somatic KRAS mutation status among older women
AU - Limburg, Paul J.
AU - Limsui, David
AU - Vierkant, Robert A.
AU - Tillmans, Lori S.
AU - Wang, Alice H.
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.
PY - 2012/4
Y1 - 2012/4
N2 - Background: Postmenopausal hormone (PMH) therapy represents a controversial colorectal cancer (CRC) preventive intervention. Because colorectal carcinogenesis is a heterogeneous process, we evaluated associations between PMH therapy and incident CRC in relation to KRAS mutation status in a population-based cohort of older women [Iowa Women's Health Study (IWHS)]. Methods: The IWHS enrolled 41,836 randomly selected women, ages 55 to 69 years, in 1986. PMH therapy and other exposure data were recorded at baseline. Tissue samples from prospectively identified CRC cases (n = 507) were analyzed for somatic KRAS mutations (exon 2, codons 12 and 13). Multivariable Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI). Results: PMH therapy (ever vs. never) was inversely associated with KRAS mutation-negative (RR = 0.83; 95% CI, 0.66-1.06; P = 0.14) and KRAS mutation-positive (RR = 0.82; 95% CI, 0.58-1.16; P = 0.27) tumors, although the observed risk estimates were not statistically significant. When anatomic subsite was additionally considered, the strongest association was found for KRAS mutation-negative, distal colorectal tumors (RR = 0.64; 95% CI, 0.43-0.96; P = 0.03). Conclusions: To our knowledge, we provide the first report of KRAS-defined CRC risks associated with PMHtherapy. These data suggest thatPMHtherapy may reduce CRC risk through mechanisms beyond KRAS mutation status but might provide greater benefits forKRASmutation-negative than mutation-positive tumors (at least in the distal colorectum). Impact: Findings from this prospective cohort study provide novel insights about the molecular biology of PMH therapy-related CRC risk reduction.
AB - Background: Postmenopausal hormone (PMH) therapy represents a controversial colorectal cancer (CRC) preventive intervention. Because colorectal carcinogenesis is a heterogeneous process, we evaluated associations between PMH therapy and incident CRC in relation to KRAS mutation status in a population-based cohort of older women [Iowa Women's Health Study (IWHS)]. Methods: The IWHS enrolled 41,836 randomly selected women, ages 55 to 69 years, in 1986. PMH therapy and other exposure data were recorded at baseline. Tissue samples from prospectively identified CRC cases (n = 507) were analyzed for somatic KRAS mutations (exon 2, codons 12 and 13). Multivariable Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI). Results: PMH therapy (ever vs. never) was inversely associated with KRAS mutation-negative (RR = 0.83; 95% CI, 0.66-1.06; P = 0.14) and KRAS mutation-positive (RR = 0.82; 95% CI, 0.58-1.16; P = 0.27) tumors, although the observed risk estimates were not statistically significant. When anatomic subsite was additionally considered, the strongest association was found for KRAS mutation-negative, distal colorectal tumors (RR = 0.64; 95% CI, 0.43-0.96; P = 0.03). Conclusions: To our knowledge, we provide the first report of KRAS-defined CRC risks associated with PMHtherapy. These data suggest thatPMHtherapy may reduce CRC risk through mechanisms beyond KRAS mutation status but might provide greater benefits forKRASmutation-negative than mutation-positive tumors (at least in the distal colorectum). Impact: Findings from this prospective cohort study provide novel insights about the molecular biology of PMH therapy-related CRC risk reduction.
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U2 - 10.1158/1055-9965.EPI-11-1168
DO - 10.1158/1055-9965.EPI-11-1168
M3 - Article
C2 - 22337533
AN - SCOPUS:84859416851
VL - 21
SP - 681
EP - 684
JO - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
SN - 1055-9965
IS - 4
ER -