Iowa Women's Health Study Research Articles

Abstract 846: Associations of dietary and lifestyle oxidative balance scores with all-cancer, all-CVD, and all-cause mortality risk among older women: The Iowa Women's Health Study

Abstract Background: Substantial basic science evidence suggests that oxidative stress may play a role in aging-related health outcomes, including cancer and cardiovascular diseases (CVD), and oxidative stress markers were linked with all-cancer, all-CVD, and all-cause mortality in epidemiologic studies. However, the associations of many individual dietary and lifestyle anti-/pro-oxidant exposures with mortality are inconsistent. Oxidative balance scores (OBS) that incorporated multiple dietary and lifestyle factors were previously developed and reported to reflect the collective oxidative effects of multiple exposures. Methods: We investigated associations of 11-component dietary and 4-component (physical activity, adiposity, alcohol, and smoking) lifestyle OBS (higher scores were considered more anti-oxidative) with all-cancer, all-CVD, and all-cause mortality among women 55 - 69 years of age at baseline in the prospective Iowa Women's Health Study (1986 - 2012). We assessed OBS-mortality associations using multivariable Cox proportional hazards regression. Results: Of the 34,137 cancer-free women included in the analytic cohort, 18,058 died (4,521 from cancer, and 6,825 from CVD) during a mean/median 22.0/26.1 person-years of follow up. Among participants in the highest relative to the lowest lifestyle OBS quintiles, the adjusted hazards ratios and their 95% confidence intervals for all-cancer, all-CVD, and all-cause mortality were 0.47 (0.43, 0.52), 0.54 (0.54, 0.58), and 0.50 (0.48, 0.53) (all Ptrend < 0.001), respectively. The associations of the dietary OBS with mortality were close to null. Conclusion: Our findings, combined with results from previous studies, suggest that a predominance of antioxidant over pro-oxidant lifestyle exposures may be associated with lower all-cancer, all-CVD, and all-cause mortality risk. Citation Format: Ziling Mao, Anna E. Prizment, DeAnn Lazovich, Boberd M. Bostick. Associations of dietary and lifestyle oxidative balance scores with all-cancer, all-CVD, and all-cause mortality risk among older women: The Iowa Women's Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 846.

Associations of dietary and lifestyle oxidative balance scores with mortality risk among older women: the Iowa Women's Health Study.

Substantial basic science evidence suggests that oxidative stress may play a role in aging-related health outcomes, including cardiovascular diseases (CVD) and cancer, and oxidative stress markers were linked with all-cause and cause-specific mortality in epidemiologic studies. However, the associations of many individual dietary and lifestyle anti-/pro-oxidant exposures with mortality are inconsistent. Oxidative balance scores (OBS) that incorporated multiple dietary and lifestyle factors were previously developed and reported to reflect the collective oxidative effects of multiple exposures. We investigated associations of 11-component dietary and 4-component (physical activity, adiposity, alcohol, and smoking) lifestyle OBS (higher scores were considered more anti-oxidative) with all-cause and cause-specific mortality among women 55-69years of age at baseline in the prospective Iowa Women's Health Study (1986-2012). We assessed OBS-mortality associations using multivariable Cox proportional hazards regression. Of the 34,137 cancer-free women included in the analytic cohort, 18,058 died (4521 from cancer, and 6825 from CVD) during a mean/median 22.0/26.1 person-years of follow-up. Among participants in the highest relative to the lowest lifestyle OBS quintiles, the adjusted hazards ratios and their 95% confidence intervals for all-cause, all-cancer, and all-CVD mortality were 0.50 (0.48, 0.53), 0.47 (0.43, 0.52), and 0.54 (0.50, 0.58) (all Ptrend < 0.001), respectively. The associations of the dietary OBS with mortality were close to null. Our findings, combined with results from previous studies, suggest that a predominance of antioxidant over pro-oxidant lifestyle exposures may be associated with lower all-cause, all-CVD, and all-cancer mortality risk.

Novel Dietary and Lifestyle Inflammation Scores Directly Associated with All-Cause, All-Cancer, and All-Cardiovascular Disease Mortality Risks Among Women

Exogenous exposures collectively may contribute to chronic, low-grade inflammation and increase risks for major chronic diseases and mortality. We previously developed, validated, and reported a novel, FFQ-based and lifestyle questionnaire-based, inflammation biomarker panel-weighted, predominantly whole foods-based 19-component dietary inflammation score (DIS) and 4-component lifestyle inflammation score (LIS; comprising physical activity, alcohol intake, BMI, and current smoking status). Both scores were more strongly associated with circulating biomarkers of inflammation in 3 populations than were previously reported dietary inflammation indices. Associations of the DIS and LIS with mortality risk have not been reported. To investigate separate and joint associations of the DIS and LIS with all-cause, all-cancer, and cardiovascular disease (CVD) mortality risks in the prospective Iowa Women's Health Study (1986-2012; n=33,155 women, ages 55-69 years, of whom 17,431 died during follow-up, including 4379 from cancer and 6574 from CVD). We summed each study participant's scores' components, weighted by their published weights, to yield the participant's inflammation score; a higher score was considered more pro-inflammatory. We assessed DIS and LIS mortality associations using multivariable Cox proportional hazards regression. Among participants in the highest relative to the lowest DIS and LIS quintiles, the adjusted HRs for all-cause mortality were 1.11 (95% CI: 1.05-1.16) and 1.60 (95% CI: 1.53-1.68), respectively; for all-cancer mortality were 1.07 (95% CI: 0.97-1.17) and 1.51 (95% CI: 1.38-1.66), respectively; and for CVD mortality were 1.12 (95% CI: 1.03-1.21) and 1.79 (95% CI: 1.66-1.94), respectively (all Ptrend values<0.01). Among those in the highest relative to the lowest joint LIS/DIS quintiles, the HRs for all-cause, all-cancer, and all-CVD mortality were 1.88 (95% CI: 1.71-2.08), 1.82 (95% CI: 1.50-2.20), and 1.92 (95% CI: 1.64-2.24), respectively. More pro-inflammatory diets and lifestyles, separately but especially jointly, may be associated with higher all-cause, all-cancer, and all-CVD mortality risks among women.

Associations between tissue-based CD3+ T-lymphocyte count and colorectal cancer survival in a prospective cohort of older women.

Tumor-infiltrating lymphocytes in colorectal cancer (CRC) predict better survival. However, associations between T-lymphocyte count in histologically normal tissues from patients with CRC and survival remain uncertain. We examined associations of CD3+ T-cells in colorectal tumor and histologically normal tissues with CRC-specific and all-cause mortality in the prospective Iowa Women's Health Study. Tissue microarrays were constructed using paraffin-embedded colorectal tissue samples from 464 women with tumor tissues and 314 women with histologically normal tissues (55-69 years at baseline) diagnosed with incident CRC from 1986 to 2002 and followed through 2014 (median follow-up 20.5 years). Three tumor and two histologically normal tissue cores for each patient were immunostained using CD3+ antibody and quantified, and the counts were averaged across the cores in each tissue. Cox proportional hazards regression estimated hazard ratios (HR) and 95% confidence interval (CI) for CRC-specific and all-cause mortality. After adjustment for age at diagnosis, body mass index, smoking status, tumor grade, and stage, HRs (95% CI) for the highest versus lowest tertile of tumor CD3+ score were 0.59 (0.38-0.89) for CRC-specific mortality and 0.82 (0.63-1.05) for all-cause mortality; for histologically normal CD3+ score, the corresponding HRs (95% CI) were 0.47 (0.19-1.17) and 0.50 (0.27-0.90), respectively. The CD3+ score combining the tumor and histologically normal scores was inversely associated with CRC-specific and all-cause mortality. Although the association between tumor CD3+ score and all-cause mortality was not significant, both higher CD3+ T-lymphocyte counts in tumor and histologically normal scores tended to be associated with lower CRC-specific and all-cause mortality.

Impact of residential mobility on estimated environmental exposures in a prospective cohort of older women.

We evaluated residential mobility in the Iowa Women's Health Study (age 55-69 years) over 19 years of follow-up (1986-2004). We assessed several environmental exposures of varying spatial scales at enrollment and follow-up addresses. Exposures included average nitrate concentrations in public water supplies, percent of agricultural land (row crops and pasture/hay) within 750 m, and the presence of concentrated animal feeding operations within 5 km. In comparison to gold standard duration-based exposures averaged across all residences, we evaluated the sensitivity and specificity of exposure metrics and attenuation bias for a hypothetical nested case-control study of cancer, which assumed participants did not move from their enrollment residence. Among 41,650 participants, 32% moved at least once during follow-up. Mobility was predicted by working outside the home, being a former/current smoker, having a higher education level, using a public drinking water supply, and town size of previous residence. Compared with duration-based exposures, the sensitivity and specificity of exposures at enrollment ranged from 94% to 99% and 97% to 99%, respectively. A hypothetical true odds ratio of 2.0 was attenuated 8% for nitrate, 9%-10% for agricultural land, and 6% for concentrated animal feeding operation exposures. Overall, we found low rates of mobility and mobility-related exposure misclassification in the Iowa Women's Health Study. Misclassification and attenuation of hypothetical risk estimates differed by spatial variability and exposure prevalence.

Abstract 4645: Lifestyle and dietary oxidative balance scores and risk for incident colorectal cancer among older women: The Iowa Women's Health Study

Abstract Background: Basic science literature strongly supports a role of oxidative stress in colorectal cancer (CRC) etiology; however, in epidemiologic studies, associations of individual lifestyle and dietary anti- and pro-oxidant exposures with CRC have been largely inconsistent. However, recent epidemiologic evidence suggests that the collective effects of these exposures on oxidative balance and CRC risk may be substantial. Methods: From lifestyle and food frequency questionnaire data from the prospective Iowa Women's Health Study (1986 - 2012), we calculated equal-weight, 4-component lifestyle and 11-component dietary oxidative balance scores (OBS), and investigated their separate and joint associations with incident CRC using multivariable Cox proportional hazards regression. Results: Of the 34,135 cancer-free women aged 55 to 69 at baseline, 1,635 developed CRC during follow-up. Among participants in the highest lifestyle and dietary OBS quintiles (higher anti-oxidant relative to pro-oxidant exposures) relative to the lowest, the multivariable-adjusted hazard ratios (HRs) were, respectively, 0.63 (95% confidence interval (CI), 0.54-0.73; Ptrend &amp;lt; 0.0001) and 0.77 (95% CI, 0.64-0.94; Ptrend = 0.01. The lowest risk was among those in the highest relative to the lowest joint lifestyle/dietary OBS quintile (HR = 0.47; 95% CI, 0.29-0.76). Conclusions: Our findings suggest that a predominance of antioxidant over pro-oxidant lifestyle and dietary exposures–especially lifestyle separately and jointly with dietary exposures–may be inversely associated with CRC risk among older women. Citation Format: Ziling Mao, Anna E. Prizment, DeAnn Lazovich, David C. Gibbs, Roberd M. Bostick. Lifestyle and dietary oxidative balance scores and risk for incident colorectal cancer among older women: The Iowa Women's Health Study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4645.

Effects of cancer history on functional age and mortality.

Cancer, its treatment, and associated adverse effects may accelerate the functional aging of cancer survivors. In the current study, the authors used geriatric assessment (GA) to compare the functional age of long-term cancer survivors with that of similarly aged women without a cancer history, and to examine whether functional age influences all-cause mortality differently between these 2 groups. Participants included 1723 cancer survivors and 11,145 age-matched, cancer-free women enrolled in the Iowa Women's Health Study in 1986 who completed the 2004 questionnaire (at ages 73-88years). GA domain deficits included ≥2 physical function limitations, ≥2 comorbidities, poor general health, poor mental health, and underweight. The risk of all-cause mortality was estimated for deficits in each GA domain between 4 groups based on the cross-classification of the presence and/or absence of cancer history and GA domain deficit (the referent group was cancer-free women without a GA deficit). Both cancer history and GA domain deficits significantly predicted 10-year mortality for all GA domains. Cancer survivors without deficits had a 1.3-fold to 1.4-fold risk of mortality, similar to the 1.1-fold to 1.7-fold risk noted among cancer-free women with deficits (all P<.05). Cancer survivors with deficits were found to have the highest mortality risk for 4 of 5 domains (hazard ratio range, 1.6-2.0). Mortality risk increased with the increasing number of GA deficits, which was greater in cancer survivors compared with cancer-free women. Even without GA deficits, cancer survivors appear to have an excess risk of death compared with women without cancer, and these deficits add to mortality risk. Interventions are needed to maintain or improve functional/physiological capacity as women age, especially in cancer survivors.

Associations of calcium and dairy product intakes with all-cause, all-cancer, colorectal cancer and CHD mortality among older women in the Iowa Women's Health Study.

Ca and dairy product intakes may be inversely associated with all-cause and cause-specific mortality, and non-Ca components of dairy products, such as insulin-like growth factor-1, may be independently associated with mortality. We investigated associations of Ca and dairy product intakes with all-cause, all-cancer, colorectal cancer (CRC) and CHD mortality among 35 221 55- to 69-year-old women in the prospective Iowa Women's Health Study, who were cancer-free in 1986. We assessed diet using a Willett FFQ, and associations using multivariable Cox proportional hazards regression. We estimated residuals from linear regression models of dairy products with dietary Ca to investigate total and specific dairy products independent of their Ca content. Through 2012, 18 687 participants died, including 4665 from cancer (including 574 from CRC) and 3603 from CHD. For those in the highest relative to the lowest quintiles of intake, the multivariable-adjusted hazard ratios (HR) and 95 % CI for total Ca (dietary plus supplemental) were 0·88 (0·83, 0·93; P trend=0·001) for all-cause mortality, 0·91 (0·81, 1·02; P trend=0·34) for all-cancer mortality, 0·60 (0·43, 0·83; P trend=0·002) for CRC mortality and 0·73 (0·64, 0·83; P trend &lt;0·0001) for CHD mortality. The corresponding HR for associations of whole milk, whole milk residuals, and low-/non-fat milk residuals with all-cause mortality were 1·20 (95 % CI 1·13, 1·27), 1·20 (95 % CI 1·13, 1·28) and 0·91 (95 % CI 0·86, 0·96), respectively. These results suggest that Ca may be associated with lower risk of all-cause, CRC and CHD mortality, and that non-Ca components of milk may be independently associated with mortality.

Ingested nitrate, disinfection by-products, and risk of colon and rectal cancers in the Iowa Women's Health Study cohort

BackgroundN-nitroso compounds (NOC) formed endogenously after nitrate/nitrite ingestion and disinfection by-products (DBPs) are suspected colorectal carcinogens, but epidemiologic evidence of these associations is limited. ObjectivesWe investigated the relationship between drinking water exposures and incident colorectal cancers in a cohort of postmenopausal women. MethodsUsing historical nitrate-nitrogen (NO3-N) measurements and estimates of total trihalomethanes (TTHM), the sum of 5 or 6 haloacetic acids (HAAs), and individual DBPs in public water supplies (PWS), we computed average exposures and years of exposure above one-half the U.S. maximum contaminant level (>1/2-MCL; >5 mg/L NO3-N and >40 μg/L TTHM). Nitrate/nitrite intakes from dietary sources were estimated using a food frequency questionnaire. We estimated hazard ratios (HR) and 95% confidence intervals (CI) from Cox regression models. We assessed NO3-N interactions with DBPs and with factors influencing endogenous NOC formation. ResultsWe identified 624 colon and 158 rectal cancers (1986–2010) among 15,910 women reporting PWS use >10 years. Ingestion of NO3-N from drinking water was not associated with risk. Colon cancer risks were non-significantly associated with the average TTHM levels >17.7 μg/L (HRQ5vsQ1 = 1.13, CI = 0.89–1.44; ptrend = 0.11) and were elevated for any duration of exposure >1/2-MCL. Rectal cancer risks were associated with the highest TTHM levels (HRQ5vsQ1 = 1.71, CI = 1.00–2.92; ptrend = 0.22) but not with years >1/2-MCL. Bromodichloromethane (HRQ4vsQ1 = 1.89, CI = 1.17–3.00; ptrend = 0.09) and trichloroacetic acid (HRQ4vsQ1 = 1.92, CI = 1.20–3.09; ptrend = 0.18) levels were also associated with risk of rectal cancer. We found no evidence of interaction between TTHM and NO3-N on the risk of either cancer. Dietary analyses yielded a positive colon cancer association with red meat, but not with processed meat intake or estimated nitrate/nitrite from specific dietary sources. ConclusionsOur results suggest that exposure to TTHM in drinking water is associated with increased risk of rectal cancer. Positive findings for individual THMs and HAAs for both colon and rectal cancers require replication in other studies. We found no associations for nitrate overall or in subgroups with presumed higher NOC exposure.

Combined Mineral Intakes and Risk of Colorectal Cancer in Postmenopausal Women.

Despite considerable biological plausibility, other than for calcium, there are few reported epidemiologic studies on mineral intake-colorectal cancer associations, none of which investigated multiple minerals in aggregate. Accordingly, we incorporated 11 minerals into a mineral score and investigated its association with incident colorectal cancer in the Iowa Women's Health Study, a prospective cohort study of 55- to 69-year-old women who completed a food frequency questionnaire in 1986. In the analytic cohort (n = 35, 221), 1,731 incident colorectal cancer cases were identified via the State Health Registry of Iowa. Participants' calcium, magnesium, manganese, zinc, selenium, potassium, and iodine intakes were ranked 1 to 5, with higher ranks indicating higher, potentially anticarcinogenic, intakes, whereas for iron, copper, phosphorus, and sodium intakes, the rankings were reversed to account for their possible procarcinogenic properties. The rankings were summed to create each woman's mineral score. The mineral score-incident colorectal cancer association was estimated using multivariable Cox proportional hazards regression. There was decreasing risk with an increasing score (P trend = 0.001). The hazard ratios and 95% confidence intervals (CI) for those in mineral score quintiles 2 to 5 relative to those in the lowest were 0.91 (CI, 0.88-1.08), 0.85 (CI, 0.75-0.95), 0.86 (CI, 0.75-0.97), and 0.75 (CI, 0.71-0.95), respectively. Our findings suggest that a predominance of putative anti- relative to pro-colorectal carcinogenic mineral intakes may be inversely associated with colorectal cancer risk. These results support further investigation of colorectal cancer etiology using composite mineral intake scores.

Evolutionary-Concordance Lifestyle and Diet and Mediterranean Diet Pattern Scores and Risk of Incident Colorectal Cancer in Iowa Women.

Background: Whereas diet and lifestyle are strongly implicated in the etiology of colorectal cancer, single exposures generally are weakly and inconsistently associated with the disease. Exposure patterns may be more helpful for investigating diet and lifestyle-colorectal cancer associations. Evolutionary-concordance diet and Mediterranean diet pattern scores were previously found to be inversely associated with colorectal adenoma.Methods: To investigate associations of these diet scores and an evolutionary-concordance lifestyle score (comprising smoking status, physical activity, and body mass index) with incident colorectal cancer, we analyzed data from the prospective Iowa Women's Health Study. Diet and lifestyle scores were calculated for each participant and categorized into quintiles, and associations estimated using Cox proportional hazards models.Results: Of the 35,221 55- to 69-year-old cancer-free women at baseline, 1,731 developed colorectal cancer during follow-up. The multivariable-adjusted HR comparing persons in the highest relative to the lowest quintile of the lifestyle score was 0.66 (95% confidence interval, 0.56-0.78; P trend < 0.01). Although the estimated associations of the evolutionary-concordance diet and Mediterranean diet scores alone with colorectal cancer were null, relative to those in the lowest tertiles of both the evolutionary-concordance diet and lifestyle scores, those in the highest tertiles of both scores were at the lowest risk (P interaction < 0.01).Conclusions: Our findings suggest that a more evolutionary-concordant lifestyle, alone and in interaction with a more evolutionary-concordant diet pattern, may be inversely associated with colorectal cancer risk.Impact: These results support further investigation of colorectal cancer etiology using evolutionary-concordance dietary and lifestyle pattern scores. Cancer Epidemiol Biomarkers Prev; 27(10); 1195-202. ©2018 AACR.

Urban vs rural residency and allergy prevalence among adult women: Iowa Women's Health Study

Abstract Background The association between residence and allergy has been well studied in children living on a farm; however, studies of this association in late adulthood are lacking. Objective This study examined the association between residence and allergy in 25,393 women aged 55-69 years in the large prospective Iowa Women's Health Study (IWHS). Methods IWHS questionnaires collected information on socio-demographic and anthropometric characteristics, medical history, lifestyle behaviors, dietary intake, residence and allergy. Residence reported at baseline (1986) was categorized into 5 groups based on living on a farm, rural, or urban areas and population size. Allergy was determined from four self-reported questions about physician-diagnosed asthma, hay fever, skin allergy, and other allergy. Logistic regression was used to determine significant risk factors for allergy and prevalence odds ratios (OR) and 95% confidence intervals (CI) for allergy associated with residence. Results Compared to large city of >10,000 residents, those living on farm, rural and smaller urban areas had decreased odds ratios of overall, skin, and other allergy in age and multivariable-adjusted models. The multivariable ORs (95% CI) for farm versus large city were decreased for overall allergy: 0.72 (0.66, 0.78) and all allergy types including asthma: 0.87 (0.75, 1.00), hay fever: 0.77 (0.69, 0.88), skin: 0.76 (0.68, 0.86), and other allergy: 0.76 (0.68, 0.86). Conclusion This study supports a hypothesis that farm living is inversely associated with allergy, suggesting that environmental exposures may protect against allergy not only in childhood, but also in late adulthood.

Cardiovascular disease mortality among women with endometrial cancer in the Iowa Women's Health Study.

Obesity is associated with endometrial cancer (EC) development and cardiovascular disease (CVD) mortality. As the number of obese EC survivors continues to increase, an examination of CVD mortality in this vulnerable population is warranted. In the Iowa Women's Health Study (1986-2011), we examined CVD mortality among 552 women with EC compared with 2,352 age- and body mass index-matched women without EC (controls). Hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD mortality were estimated using multivariable-adjusted Cox proportional hazards regression models stratified by an indicator for match set. Compared to controls, women with EC more often reported a history of diabetes, hypertension, and never smoking. Compared with controls, women with EC had lower CVD mortality (HR 0.75, 95% CI 0.56-0.99), and higher all-cause mortality (HR 1.50, 95% CI 1.30-1.74). Although some CVD risk factors were more common in women with versus without EC, CVD mortality was lower among the former group. Additional well-adjusted analyses with larger study populations are needed to understand interactions between CVD risk factors with CVD mortality among EC survivors. The CVD risk factor profile of EC survivors warrants emphasis on cardiovascular health.

Abstract 5313: Associations of calcium and dairy product intakes with colorectal cancer risk among older women: the Iowa Women's Health Study

Abstract Calcium has been consistently modestly associated with lower risk of colorectal cancer, which remains the second leading cause of cancer deaths among men and women combined in the United States. Dairy products, a major source of dietary calcium, have also been consistently inversely associated with colorectal cancer, although inconsistencies in relation to high-fat dairy products have been noted. Limited evidence suggests that dairy products may contain components other than calcium and fat, such as insulin-like growth factor 1 (IGF-1), that may be independently directly associated with risk of colorectal and other cancers. Data from the Iowa Women’s Health Study, a prospective cohort study, were used to investigate associations of calcium, dairy products, and the non-calcium component of dairy products with colorectal cancer incidence. Dietary data were collected using a semiquantitative food frequency questionnaire (FFQ) mailed to 55 – 69 year-old women in 1986 who had a valid Iowa driver’s license. Among participants with no history of cancer at baseline and who satisfactorily completed their FFQ (n=35,221), through follow up in 2012, 1,731 incident cases of colorectal cancer were documented via the Iowa SEER registry. To investigate total dairy and total, whole, and non-fat milks independent of their calcium components, we used the residuals from linear regression models of their associations with dietary calcium. Associations of the calcium and dairy product variables with colorectal cancer incidence were estimated using multivariable Cox proportional hazards regression. For those in the highest relative to those in the lowest quintiles of intakes, the adjusted hazards ratios and 95% confidence intervals (CI) were 0.81 (CI 0.67-0.98; P-trend 0.004) for total calcium, 0.85 (CI 0.68-1.03; P-trend 0.07) for dietary calcium, and 0.85 (CI 0.68-1.06; P-trend 0.16) for supplemental calcium. For total dairy and total milk, the corresponding findings were 0.79 (CI 0.66-0.94; P-trend 0.01) and 0.82 (CI 0.69-0.96; P-trend 0.09), respectively. Low-fat dairy products, non-fat milk, and residuals of total dairy products and total and non-fat milk were not associated with colorectal cancer. These results are consistent with previous findings of lower colorectal cancer risk with higher intakes of calcium and dairy products, but provide little support for the hypothesis that the non-calcium, non-fat component of dairy products may be associated with colorectal cancer. Citation Format: Caroline Um, Anna Prizment, DeAnn Lazovich, Roberd M. Bostick. Associations of calcium and dairy product intakes with colorectal cancer risk among older women: the Iowa Women's Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5313. doi:10.1158/1538-7445.AM2017-5313

Dietary inflammatory index and risk of renal cancer in the Iowa Women’s Health Study

The association between inflammatory potential of diet and renal cancer risk has not been investigated. In this study, we explored the association between the dietary inflammatory index (DII) and risk of renal cancer in the Iowa Women's Health Study. From 1986 to 2011, 33,817 women initially recruited at 55-69years of age were followed for incident renal cancers (n = 263). The DII was computed based on dietary intake assessed using a reproducible and valid 121-item food frequency questionnaire. Cox proportional hazards regression was used to estimate hazard ratios (HR) adjusting for age, body mass index, energy intake, smoking status, education, pack years of smoking, hypertension, and hormone replacement therapy. Multivariable analyses revealed positive association between higher DII scores and renal cancer risk (HR for DIIcontinuous: 1.07 per unit increase in DII (corresponding to 10% change in the DII range in the current study); 95% CI 1.00, 1.15; HR for DIItertile3vs1 = 1.52; 95% CI 1.09, 2.13). Stratified analyses produced slightly stronger associations between DII and renal cancer risk among women with BMI <30kg/m2 (HRTertile3vs1 = 1.57; 95% CI = 1.04, 2.36) and ever smokers (HRtertile3vs1 = 2.35; 95% CI = 1.22, 4.55), although the corresponding interaction p values were not significant. Pro-inflammatory diet, as indicated by higher DII scores, was associated with increased renal cancer risk.

Prospective study of the dietary inflammatory index and risk of breast cancer in postmenopausal women.

Diet in relation to breast cancer etiology has been studied widely, but results have remained inconsistent. Various dietary components including fruits, vegetables, and meat have been implicated through their effects on inflammation. Using data from the Iowa Women's Health Study we examine prospectively the association between the dietary inflammatory index (DII) and breast cancer incidence. DII scores were computed based on baseline dietary intake assessed by a validated 121-item food frequency questionnaire in a cohort of 34700 women, aged 55-69 years at recruitment in 1986 and followed for incident breast cancer. During the 25-year follow-up period (1986-2011), 2910 incident breast cancer cases were identified. We used Cox proportional hazards regression to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CI). We found positive associations between DII scores and breast cancer risk (HR for DIItertiles : T3 vs T1 = 1.11; 95% CI: 1.00, 1.22), with stronger associations in obese women (HR for DIIcontinuous : 1.05 per unit increase in DII; 95% CI: 1.02, 1.12; HR for DIItertiles : T3 vs T1 = 1.35; 95% CI: 1.10, 1.66, p-value for interaction = 0.02). A proinflammatory diet, as indicated by higher DII scores, appears to increase the risk of developing breast cancer, especially in obese postmenopausal women.

Aspirin use and the incidence of breast, colon, ovarian, and pancreatic cancers in elderly women in the Iowa Women's Health Study.

Few studies have evaluated the chemopreventive effect of aspirin on the cancer risk in elderly women. We examined associations between frequency, dose, and duration of aspirin use with incidence of 719 aspirin-sensitive cancers (cancers of colon, pancreas, breast, and ovaries) in the Iowa Women's Health Study (IWHS), a prospective cohort of women over 70years old. Aspirin frequency, dose, and duration were self-reported in the 2004 IWHS questionnaire. Women were followed-up to 2011. Cancer cases were ascertained by linkage to the Iowa State Health Registry. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Among the 14,386 women, 30% were nonusers of aspirin; 34% used low-dose aspirin, and 36% used regular- or high-dose aspirin. Compared with nonuse of aspirin, the HRs (95% CI) for incidence of aspirin-sensitive cancers were 0.87 (0.72-1.06) for regular to high doses of aspirin use, 0.95 (0.80-1.13) for aspirin use 6+ times per week, and 0.93 (0.74-1.17) for aspirin use for 10+ years. For cumulative aspirin use, HR (95% CI) was 0.87 (0.70-1.09) for >60,000mg of aspirin per year and 0.95 (0.75-1.21) for >280,000mg of aspirin in their lifetime, versus nonuse of aspirin. Results were similar for the all-cause cancer death as an endpoint, with a significant inverse association observed between lifetime aspirin dose and cancer mortality [<95,000mg vs nonuser HR 0.76 (0.61-0.95)]. These findings suggest that aspirin use may prevent incident breast, colon, pancreatic, and ovarian cancer in elderly women.

Abstract 2636: Tumor-infiltrating cytotoxic T-cells are associated with improved survival of colorectal cancer patients

Abstract Background: The immune response has been shown to impact the course of colorectal cancer (CRC). Our goal was to examine the survival of CRC patients in relation to tumor-infiltrating cytotoxic (CD8+) T lymphocytes (CTL). We quantified CTLs in tumor epithelial and stromal tissues and correlated them with clinicopathological characteristics and survival of CRC patients in the Iowa Women's Health Study. Methods: Paraffin-embedded tissue samples were available from 465 post-menopausal women diagnosed with incident CRC in 1986-2002. Tumor microarrays were constructed and immunostained with a CD8 antibody (Clone 144B; Dako). CTLs in tumor epithelial and stromal tissues were categorized by an experienced pathologist into non-detected; mild (1-10 cells per core); moderate (11-29 cells); and strong infiltration (≥30 cells per core), and averaged over cores per each person. We used Cox regression to estimate the hazard ratio (HR) and 95% CI for total and CRC death in relation to each CTL score after adjusting for age of diagnosis, SEER stage, grade, body mass, smoking history and integrated molecular pathway for CRC. The tumors were categorized by integrated pathway (traditional, alternate, serrated, unassigned) based on the combination of phenotypes: microsatellite instability (MSI) status, CpG island methylator (CIMP) phenotype; and mutations in BRAF and/or KRAS genes (described in Samadder, 2013). Results: During follow-up until 2011, 31% of participants died from CRC, 36% from all other causes, and 33% were alive (median follow-up: 8.4 y). The Spearman correlation coefficient between epithelial and stromal CTL scores was 0.52. Both scores were inversely correlated with stage at diagnosis and were higher in tumors characterized by MSI-high, CIMP-high and BRAF mutation-positive status. The highest categories in the epithelial and stromal scores were associated with statistically significant decreases in total death (by 44% and 40%, respectively) and CRC death (by 68% and 56%, respectively) compared to lowest categories. After summing epithelial and stromal CTL scores, the combined HRs (95% CI) in the highest versus lowest category were 0.55 (0.38-0.78) for total death (p-trend = 0.0002) and 0.36 (0.20-0.63) for CRC death (p-trend&amp;lt;0.0001). Additional adjustment for surgery, chemotherapy, radiation, and comorbidities did not markedly change the associations. Finally, there was a statistically significant quantitative interaction between stromal score and MSI status in relation to total and CRC death (P for interaction were 0.02 and 0.0001, respectively); HRs were lower for MSI-high than for MS-stable tumors. There was also a significant interaction between smoking status (current versus never) and epithelial CTL score: the HRs for total and CRC death were lowest among never smokers with the highest score. Conclusions. Our study further supports infiltration of tumors with CTLs as an important prognostic factor in CRC. Citation Format: Anna E. Prizment, Robert A. Vierkant, Thomas C. Smyrk, Lori S. Tillmans, Heather H. Nelson, Charles F. Lynch, Stephen N. Thibodeau, Timothy R. Church, James R. Cerhan, Kristin E. Anderson, Paul J. Limburg. Tumor-infiltrating cytotoxic T-cells are associated with improved survival of colorectal cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2636.

Atrazine in public water supplies and risk of ovarian cancer among postmenopausal women in the Iowa Women's Health Study

BackgroundFew studies have evaluated environmental chemical exposures in relation to ovarian cancer. We previously found an increased risk of ovarian cancer among postmenopausal women in Iowa associated with higher nitrate...

Tumor eosinophil infiltration and improved survival of colorectal cancer patients: Iowa Women's Health Study

The role of the innate immune response in colorectal cancer is understudied. We examined the survival of colorectal cancer patients in relation to eosinophils, innate immune cells, infiltrating the tumor. Tissue microarrays were constructed from paraffin-embedded tumor tissues collected between 1986 and 2002 from 441 post-menopausal women diagnosed with colorectal cancer in the Iowa Women's Health Study. Tissue microarrays were stained with an eosinophil peroxidase antibody. Eosinophils in epithelial and stromal tissues within the tumor (called epithelial and stromal eosinophils, hereafter) were counted and scored into three and four categories, respectively. In addition, the degree of eosinophil degranulation (across epithelial and stromal tissues combined) was quantified and similarly categorized. We used Cox regression to estimate the hazard ratios and 95% confidence interval for all-cause and colorectal cancer death during 5-year follow-up after diagnosis and during follow-up through 2011 (‘total follow-up'). The hazard ratios associated with eosinophil scores were adjusted for age of diagnosis, SEER (Surveillance, Epidemiology, and End Results) stage, tumor grade, body mass, and smoking history. High tumor stromal eosinophil score was inversely correlated with age and stage, and was associated with a decreased risk for all-cause and colorectal cancer death: hazard ratios (95% confidence intervals) were 0.61 (0.36–1.02; P-trend=0.02) and 0.48 (0.24–0.93; P-trend=0.01), respectively, during the 5-year follow-up for the highest vs lowest category. The inverse associations also existed for total follow-up for all-cause and colorectal cancer death for the highest vs lowest stromal eosinophil score: hazard ratios (95% confidence intervals) were 0.72 (0.48–1.08; P-trend=0.04) and 0.61 (0.34–1.12; P-trend=0.04), respectively. Further adjustment for treatment, comorbidities, additional lifestyle factors, tumor location, or molecular markers did not markedly change the associations, while adjustment for cytotoxic T cells slightly attenuated all associations. The infiltration of tumors with eosinophils, especially in stromal tissue, may be an important prognostic factor in colorectal cancer.