Anderson, Kristin E.

Abstract Increased alcohol consumption is a putative colorectal cancer (CRC) risk factor. However, existing data are less conclusive for women than men. Also, to date, relatively few studies have reported alcohol-related CRC risks based on molecularly defined tumor subtypes. We evaluated associations between alcohol intake and incident CRC, overall and by microsatellite instability [MSI high (MSI-H) or MSI low/microsatellite stable (MSI-L/MSS)], CpG island methylator phenotype (CIMP positive or CIMP negative), and BRAF mutation (mutated or wild-type) status in the prospective, population-based Iowa Women's Health Study (IWHS; n = 41,836). Subjects were 55 to 69 years at baseline (1986), and exposure data were obtained by self-report. Incident CRCs were prospectively identified and archived, paraffin-embedded tissue specimens were collected from 732 representative cases, diagnosed through December 31, 2002. Multivariate Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI). Among alcohol consumers, the median intake (range) was 3.4 (0.9–292.8) g/d. Compared with nonconsumers, alcohol intake levels of 3.4 g/d or less (RR = 1.00; 95% CI, 0.86–1.15) and more than 3.4 g/d (RR = 1.06; 95% CI, 0.91–1.24) were not significantly associated with overall CRC risk. Analyses based on alcohol intake levels of 30 g/d or less and more than 30 g/d or quartile distributions yielded similar risk estimates. Null associations were also observed between each alcohol intake level and the MSI-, CIMP- or, BRAF-defined CRC subtypes (P > 0.05 for each comparison). These data do not support an adverse effect from alcohol intake on CRC risk, overall or by specific molecularly defined subtypes, among older women. Cancer Prev Res; 4(12); 2035–43. ©2011 AACR.

AbstractAspirin and other nonsteroidal anti-inflammatory drugs (NSAID) show indisputable promise as cancer chemoprevention agents. However, studies have been inconsistent as to whether aspirin has a protective effect in development of pancreatic cancer. To further evaluate the association between aspirin, NSAID, and acetaminophen use with pancreatic cancer risk, we used a clinic-based case–control study of 904 rapidly ascertained histologically or clinically documented pancreatic ductal adenocarcinoma cases, and 1,224 age- and sex-matched healthy controls evaluated at Mayo Clinic from April 2004 to September 2010. Overall, there is no relationship between non-aspirin NSAID or acetaminophen use and risk of pancreatic cancer. Aspirin use for 1 d/mo or greater was associated with a significantly decreased risk of pancreatic cancer (OR = 0.74, 95% CI: 0.60–0.91, P = 0.005) compared with never or less than 1 d/mo. Analysis by frequency and frequency-dosage of use categories showed reduced risk (P = 0.007 and 0.022, respectively). This inverse association was also found for those who took low-dose aspirin for heart disease prevention (OR = 0.67, 95% CI: 0.49–0.92, P = 0.013). In subgroup analyses, the association between aspirin use and pancreatic cancer was not significantly affected by pancreatic cancer stage, smoking status, or body mass index. Our data suggest that aspirin use, but not non-aspirin NSAID use, is associated with lowered risk of developing pancreatic cancer. Cancer Prev Res; 4(11); 1835–41. ©2011 AACR.

Abstract Pancreatic cancer is a devastating disease for which the role of dietary risk factors remains inconclusive. We evaluated fruit, vegetable, fiber, and grain consumption with pancreatic cancer risk using a clinic-based case-control design, excluding participants who reported changing their diet within 5 years prior to entering the study. Our study included 384 rapidly ascertained cases and 983 non-cases (frequency matched on age at time of recruitment (± 5 years), race, sex, and region of residence) who completed epidemiologic surveys and a 144-item food frequency questionnaire developed by the National Cancer Institute. Logistic regression was used to calculate odds ratios (OR) and 95% CIs, adjusted for age, sex, smoking, body mass index, energy intake, and alcohol consumption. Comparing highest to lowest quintiles, we observed significant (OR < 0.01) inverse associations with significant trends (ptrend < 0.01) for citrus, melon, and berries, other fruit, dark green vegetables, deep yellow vegetables, tomato, other vegetables, dry bean and pea, insoluble fiber, soluble fiber, and whole grains. Adjusting for diabetes or total sugar intake in the multivariate logistic regression model did not significantly affect results. Consuming a diet high in fruits, vegetables, fiber, and whole grains may reduce the risk of developing pancreatic cancer. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A85.

AbstractObesity is a controversial risk factor for colorectal cancer (CRC) in older women. We evaluated associations between multiple body size parameters and incident CRC in the prospective, population-based Iowa Women's Health Study (IWHS). IWHS participants, ages 55 to 69 years, provided data regarding height; weight; weight at ages 50, 40, 30, 18 years; hip circumference; and waist circumference at baseline (1986). Derived variables included body mass index (BMI), waist-to-hip ratio (WHR), and “overweight years” (OWY; conceptually similar to cigarette pack-years). Incident CRC cases (n = 1,464) were ascertained from the State Health Registry of Iowa, through 2005. Multivariable Cox regression models were fit to estimate body size–associated CRC risks. Among 36,941 women (619,961 person-years), baseline height, weight, BMI, hip circumference, waist circumference, and WHR were all positively associated with incident CRC (Ptrend ≤ 0.003 for each). Baseline BMI yielded the highest CRC risk estimates (obese III versus normal, RR = 1.56; 95% CI = 1.10–2.22; Ptrend < 0.001) and was more closely associated with distal than proximal tumors (Ptrend < 0.001 versus 0.06). Conversely, height was more closely associated with proximal than distal tumors (Ptrend < 0.001 versus 0.04). Other body size parameters were less predictive of incident CRC. These data strongly support a positive association between increased body size and CRC risk among older women. Further investigation of when increased body size has the greatest effect on CRC risk (i.e., early adulthood versus later adulthood) might also be informative, particularly with respect to defining subsite-specific pathways of colorectal carcinogenesis. Cancer Prev Res; 3(12); 1608–20. ©2010 AACR.

AbstractPrevious epidemiologic studies have reported that a history of allergy is associated with reduced risk of colorectal cancer and other malignancies. We studied the association between allergy history and incident colorectal cancer (n = 410) prospectively in 21,292 Iowa women followed for 8 years. Allergy was defined from four self-reported questions about physician-diagnosed asthma (a), hay fever (b), eczema or allergy of the skin (c), and other allergic conditions (d). A history of any allergy was inversely associated with incident colorectal cancer: after multivariate adjustment, the hazard ratio (HR) was 0.74 [95% confidence interval (95% CI), 0.59-0.94]. Compared with women with no allergy, women reporting only one of the four types of allergy and women reporting two or more types had HRs of 0.75 (95% CI, 0.56-1.01) and 0.58 (95% CI, 0.37-0.90), respectively (P trend = 0.02). The inverse association persisted in analyses restricted to any type of nonasthmatic allergy (HR, 0.73; 95% CI, 0.56-0.95). HRs were similar for rectal and colon cancers as well as for colon subsites: proximal and distal (HRs for any allergy ranged from 0.63 to 0.78 across these end points). Allergy history, which may reflect enhanced immunosurveillance, is associated with a reduced risk of colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2357–62)

Abstract Background: Previous epidemiologic studies have shown that regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with decreased colorectal cancer risk. However, few studies have examined associations between NSAID use and subsite-specific colorectal cancer risks. Because tumors of the proximal and distal colon differ with respect to their genetic alterations, clinicopathologic features, and demographic distribution, further investigation of subsite-specific colorectal cancer risks may be rewarding. Methods: Data about aspirin and nonaspirin-NSAID use were recorded by self-report in 1992 among the initially cancer-free cohort of postmenopausal women in the Iowa Women's Health Study (n = 27,160). In total, 637 women developed colorectal cancer during the 11 years of follow-up, including 365 proximal colon, 132 distal colon, and 120 rectal cancer cases (11 overlapping and 9 not specified). Results: For colon cancer, the multivariable-adjusted hazard ratios (HR) for women reporting use of aspirin two to five times and six or more times weekly (compared with nonusers of aspirin) were 0.79 [95% confidence interval (95% CI), 0.59-1.04] and 0.76 (95% CI, 0.58-1.00), respectively. The corresponding HRs for nonaspirin NSAIDs were 0.63 (95% CI, 0.41-0.96) and 0.85 (95% CI, 0.63-1.15), respectively. For proximal colon cancer, the multivariable-adjusted HRs for women reporting use of aspirin or nonaspirin NSAIDs two or more times weekly (compared with nonusers of each) were 0.67 (95% CI, 0.51-0.87) and 0.71 (95% CI, 0.52-0.97), respectively. No statistically significant association was found between either distal colon or rectal cancer and aspirin or nonaspirin NSAID use. Discussion: Our study is consistent with a limited number of prior reports that have observed stronger associations between NSAID use and proximal versus distal colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1785–90)

Abstract Background: Dietary glycemic index (GI) and glycemic load (GL) affect circulating insulin concentrations. Elevated circulating insulin concentrations can increase insulin-like growth factor-1, and both of these hormones may have growth-promoting effects within the colorectum. Methods: We examined associations of GI and GL with colorectal cancer (CRC) among participants in the Iowa Women's Health Study (n = 35,197; ages 55-69 years at baseline in 1986). Over 15 years of follow-up, we identified 757 cases of colon cancer and 209 cases of rectal cancer (954 CRC cases). Results: Overall, neither GI nor GL were significantly associated with incident CRC. However, among obese women (baseline body mass index ≥30 kg/m2) CRC incidence was increased in the highest versus lowest quintiles of GI (relative risk, 1.66; 95% confidence intervals, 1.13-2.43; P for trend = 0.02) and GL (relative risk, 1.79; 95% confidence intervals, 1.19-2.70; P for trend < 0.01). This pattern of increased risk for obese women with high GI or GL tended to hold for both colon cancer and rectal cancer, and for nondiabetic women as well. No statistically significant associations were observed between GI or GL and CRC among subjects whose baseline body mass index was <30 kg/m2. Conclusion: Our findings suggest that high GI or GL are not major CRC risk factors among older women in general, but may increase CRC risk among women who are obese. (Cancer Epidemiol Biomarkers Prev 2006;15(5):392–6)

Abstract Intervention trials with supplemental β-carotene have observed either no effect or a harmful effect on lung cancer risk. Because food composition databases for specific carotenoids have only become available recently, epidemiological evidence relating usual dietary levels of these carotenoids with lung cancer risk is limited. We analyzed the association between lung cancer risk and intakes of specific carotenoids using the primary data from seven cohort studies in North America and Europe. Carotenoid intakes were estimated from dietary questionnaires administered at baseline in each study. We calculated study-specific multivariate relative risks (RRs) and combined these using a random-effects model. The multivariate models included smoking history and other potential risk factors. During follow-up of up to 7–16 years across studies, 3,155 incident lung cancer cases were diagnosed among 399,765 participants. β-Carotene intake was not associated with lung cancer risk (pooled multivariate RR = 0.98; 95% confidence interval, 0.87–1.11; highest versus lowest quintile). The RRs for α-carotene, lutein/zeaxanthin, and lycopene were also close to unity. β-Cryptoxanthin intake was inversely associated with lung cancer risk (RR = 0.76; 95% confidence interval, 0.67–0.86; highest versus lowest quintile). These results did not change after adjustment for intakes of vitamin C (with or without supplements), folate (with or without supplements), and other carotenoids and multivitamin use. The associations generally were similar among never, past, or current smokers and by histological type. Although smoking is the strongest risk factor for lung cancer, greater intake of foods high in β-cryptoxanthin, such as citrus fruit, may modestly lower the risk.

AbstractBecause fruits and vegetables are rich in bioactive compounds with potential cancer-preventive actions, increased consumption may reduce the risk of ovarian cancer. Evidence on the association between fruit and vegetable intake and ovarian cancer risk has not been consistent. We analyzed and pooled the primary data from 12 prospective studies in North America and Europe. Fruit and vegetable intake was measured at baseline in each study using a validated food-frequency questionnaire. To summarize the association between fruit and vegetable intake and ovarian cancer, study-specific relative risks (RR) were estimated using the Cox proportional hazards model, and then combined using a random-effects model. Among 560,441 women, 2,130 cases of invasive epithelial ovarian cancer occurred during a maximum follow-up of 7 to 22 years across studies. Total fruit intake was not associated with ovarian cancer risk—the pooled multivariate RR for the highest versus the lowest quartile of intake was 1.06 [95% confidence interval (95% CI), 0.92-1.21; P value, test for trend = 0.73; P value, test for between-studies heterogeneity = 0.74]. Similarly, results for total vegetable intake indicated no significant association (pooled multivariate RR, 0.90; 95% CI, 0.78-1.04, for the highest versus the lowest quartile; P value, test for trend = 0.06; P value, test for between-studies heterogeneity = 0.31). Intakes of botanically defined fruit and vegetable groups and individual fruits and vegetables were also not associated with ovarian cancer risk. Associations for total fruits and vegetables were similar for different histologic types. These results suggest that fruit and vegetable consumption in adulthood has no important association with the risk of ovarian cancer.