Cindy K. Blair

Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults

IMPORTANCE Leisure-time physical activity has been associated with lower risk of heart-disease and all-cause mortality, but its association with risk of cancer is not well understood. OBJECTIVE To determine the association of leisure-time physical activity with incidence of common types of cancer and whether associations vary by body size and/or smoking. DESIGN, SETTING, AND PARTICIPANTS We pooled data from 12 prospective US and European cohorts with self-reported physical activity (baseline, 1987-2004). We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals for associations of leisure-time physical activity with incidence of 26 types of cancer. Leisure-time physical activity levels were modeled as cohort-specific percentiles on a continuous basis and cohort-specific results were synthesized by random-effects meta-analysis. Hazard ratios for high vs low levels of activity are based on a comparison of risk at the 90th vs 10th percentiles of activity. The data analysis was performed from January 1, 2014, to June 1, 2015. EXPOSURES Leisure-time physical activity of a moderate to vigorous intensity. MAIN OUTCOMES AND MEASURES Incident cancer during follow-up. RESULTS A total of 1.44 million participants (median [range] age, 59 [19-98] years; 57% female) and 186 932 cancers were included. High vs low levels of leisure-time physical activity were associated with lower risks of 13 cancers: esophageal adenocarcinoma (HR, 0.58; 95% CI, 0.37-0.89), liver (HR, 0.73; 95% CI, 0.55-0.98), lung (HR, 0.74; 95% CI, 0.71-0.77), kidney (HR, 0.77; 95% CI, 0.70-0.85), gastric cardia (HR, 0.78; 95% CI, 0.64-0.95), endometrial (HR, 0.79; 95% CI, 0.68-0.92), myeloid leukemia (HR, 0.80; 95% CI, 0.70-0.92), myeloma (HR, 0.83; 95% CI, 0.72-0.95), colon (HR, 0.84; 95% CI, 0.77-0.91), head and neck (HR, 0.85; 95% CI, 0.78-0.93), rectal (HR, 0.87; 95% CI, 0.80-0.95), bladder (HR, 0.87; 95% CI, 0.82-0.92), and breast (HR, 0.90; 95% CI, 0.87-0.93). Body mass index adjustment modestly attenuated associations for several cancers, but 10 of 13 inverse associations remained statistically significant after this adjustment. Leisure-time physical activity was associated with higher risks of malignant melanoma (HR, 1.27; 95% CI, 1.16-1.40) and prostate cancer (HR, 1.05; 95% CI, 1.03-1.08). Associations were generally similar between overweight/obese and normal-weight individuals. Smoking status modified the association for lung cancer but not other smoking-related cancers. CONCLUSIONS AND RELEVANCE Leisure-time physical activity was associated with lower risks of many cancer types. Health care professionals counseling inactive adults should emphasize that most of these associations were evident regardless of body size or smoking history, supporting broad generalizability of findings.

The Role of Obesity in Cancer Survival and Recurrence

Obesity and components of energy imbalance, that is, excessive energy intake and suboptimal levels of physical activity, are established risk factors for cancer incidence. Accumulating evidence suggests that these factors also may be important after the diagnosis of cancer and influence the course of disease, as well as overall health, well-being, and survival. Lifestyle and medical interventions that effectively modify these factors could potentially be harnessed as a means of cancer control. However, for such interventions to be maximally effective and sustainable, broad sweeping scientific discoveries ranging from molecular and cellular advances, to developments in delivering interventions on both individual and societal levels are needed. This review summarizes key discussion topics that were addressed in a recent Institute of Medicine Workshop entitled, “The Role of Obesity in Cancer Survival and Recurrence”; discussions included (i) mechanisms associated with obesity and energy balance that influence cancer progression; (ii) complexities of studying and interpreting energy balance in relation to cancer recurrence and survival; (iii) associations between obesity and cancer risk, recurrence, and mortality; (iv) interventions that promote weight loss, increased physical activity, and negative energy balance as a means of cancer control; and (v) future directions. Cancer Epidemiol Biomarkers Prev; 21(8); 1244–59. ©2012 AACR.

Maternal diet and infant leukemia: the DNA topoisomerase II inhibitor hypothesis: a report from the children's oncology group.

Background: The MLL 11q23 translocation arises in utero and is present in 75% of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+). Methods: This Childrens Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression. Results: There was little evidence of an association between the specific DNAt2 index and leukemia overall and by subtype. An exception was AML(MLL+); odds ratios (95% confidence intervals) comparing the second to fourth quartiles to the first were 1.9 (0.5-7.0), 2.1 (0.6-7.7), and 3.2 (0.9-11.9), respectively (P for trend = 0.10). For the vegetable and fruit index, there were significant or near-significant inverse linear trends for all leukemias combined, ALL(MLL+), and AML(MLL−). Conclusion: Overall, maternal consumption of fresh vegetables and fruits during pregnancy was associated with a decreased risk of infant leukemia, particularly MLL+. However, for AML(MLL+) cases, maternal consumption of specific DNAt2 inhibitors seemed to increase risk. Although based on small numbers, these data provide some support for distinct etiologic pathways in infant leukemia.

Dietary Inflammatory Index and Risk of Colorectal Cancer in the Iowa Women's Health Study

Background: Colorectal cancer, the third most common cancer in the United States, has a natural history that usually encompasses several decades. Dietary components have been implicated in the etiology of colorectal cancer, perhaps through their effect on inflammation. Methods: We examined the ability of the dietary inflammatory index (DII) to predict colorectal cancer in the Iowa Womens Health Study. The DII was computed based on dietary intake assessed by a 121-item food frequency questionnaire in this cohort of 34,703 women, ages 55 to 69 years, free of any self-reported prior malignancy at enrollment in 1986. Incident colorectal cancer cases were identified through linkage with the State Health Registry of Iowa (a Surveillance, Epidemiology, and End Results program member). Cox proportional hazards regression was used to estimate HRs. Through the end of 2010, 1,636 incident colorectal cancers were identified, including 1,329 colon and 325 rectal cancers. Results: Multivariable analysis, adjusting for body mass index, smoking status, pack-years of smoking, hormone replacement therapy, education, diabetes, and total energy intake, revealed positive associations between higher DII and colorectal cancer risk [HR for DIIcontinuous: 1.07 per unit increase in DII (corresponding to 0.5 SD unit increase); 95% confidence interval (CI), 1.01–1.13; HR for DIIquintiles: Q5 vs. Q1 = 1.20; 95% CI, 1.01–1.43]. HRs for DII were similar for colon cancer and rectal cancer, though not statistically significant for rectal cancer. Conclusions: These results indicate that a proinflammatory diet, as indicated by higher DII scores, was associated with higher risk of developing colorectal cancer. Impact: Proinflammatory diets are associated with increased risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 23(11); 2383–92. ©2014 AACR.

NSAID use and survival after breast cancer diagnosis in post-menopausal women

Many epidemiologic studies, although not all, have shown an inverse relation between non-steroidal anti-inflammatory drug (NSAID) use and risk of incident breast cancer, but the possible influence of NSAID use on breast cancer survival has not been evaluated. We examined the association between self-reported NSAID use and survival after invasive breast cancer diagnosis among 591 postmenopausal women in a prospective study. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer death as well as all-cause mortality associated with NSAID use. There was an indication of reduced risk of breast cancer mortality and all-cause mortality for women reporting any versus no use of NSAIDs, with multivariate-adjusted HRs of 0.64 (95% CI 0.39–1.05) and 0.57 (95% CI 0.40–0.81), respectively. There was no trend of decreasing risk of death with increasing frequency of NSAID use per week. While the results from this exploratory analysis are preliminary, there is biological plausibility for such an association. Further studies should consider whether NSAIDs, which have biological activity affecting tumor promotion and progression and appear to protect against breast cancer incidence, may be associated with better prognosis after a diagnosis of invasive breast cancer.

Anthropometric Characteristics and Risk of Multiple Myeloma

Background: Few studies have examined obesity and risk for multiple myeloma, and the results are inconsistent. Laboratory evidence suggests mechanisms through which obesity could influence carcinogenesis of this hematopoietic malignancy. Methods: We examined the association between anthropometric characteristics and incident multiple myeloma in a prospective, population-based sample of 37,083 postmenopausal women. In 1986, the women completed a mailed questionnaire that included self-report of height and weight, and friend measurement of waist and hip circumferences. During 16 years of follow up, 95 cases of multiple myeloma were identified through linkage to the Iowa Cancer Registry. Results: In an age-adjusted model, women in the highest category of several anthropometric measurements compared with the lowest category were at increased risk of developing multiple myeloma. For body mass index (kg/m2), the rate ratio (95% confidence interval) was 1.5 (0.92–2.6); for weight, 1.9 (1.1–3.4); for waist circumference, 2.0 (1.1–3.5); and for hip circumference, 1.8 (1.0–3.0). Conclusion: Greater adiposity may increase the risk of multiple myeloma.

Periconceptional vitamin use and leukemia risk in children with Down syndrome: A children's oncology group study

Periconceptional vitamin supplementation reduces the risk of neural tube defects, and possibly may reduce the risk of certain childhood malignancies, including acute lymphoblastic leukemia (ALL). Because children with Down syndrome (DS) experience a 20‐fold higher risk of leukemia than the general population, the authors evaluated whether periconceptional vitamin supplementation reduced the risk of leukemia in children with DS.

Light-intensity activity attenuates functional decline in older cancer survivors.

UNLABELLED While moderate- to vigorous-intensity physical activities (MVPA) confer the greatest health benefits, evidence suggests that light-intensity activities are also beneficial, particularly for older adults and individuals with moderate to severe comorbidities. PURPOSE To examine cross-sectional and longitudinal associations between light-intensity activity and physical function in older cancer survivors at increased risk for age- and treatment-related comorbidities, including accelerated functional decline. METHODS The analysis included data from 641 breast, prostate, and colorectal cancer survivors (54% female) age 65 yr and older who participated in a 1-yr home-based diet and exercise intervention designed to reduce the rate of physical function decline. ANCOVA was used to compare means of physical function across levels of PA intensity (low-light [LLPA]: 1.5-2.0 METs; high-light [HLPA]: 2.1-2.9 METs; MVPA: ≥3.0 METs). RESULTS In cross-sectional analyses, increasing tertiles of light-intensity activity were associated with higher scores for all three measures of physical function (all P values <0.005), after adjusting for age, sex, body mass index, comorbidity, symptoms, and MVPA. Associations were stronger for HLPA than for LLPA. Compared with survivors who had decreased MVPA or maintained stable MVPA and HLPA at the postintervention follow-up, those who had increased HLPA, but had decreased MVPA or maintained stable MVPA, reported higher physical function scores (LS means [95% confidence interval]: SF-36 Physical Function Subscale: -5.58 [-7.96 to -3.20] vs -2.54 [-5.83 to 0.75], P = 0.14; Basic Lower Extremity Function: -2.00 [-3.45 to -0.55] vs 0.28 [-1.72 to 2.28], P = 0.07; Advanced Lower Extremity Function: -2.58 [-4.00 to -1.15] vs 0.44 [-1.52 to 2.40], P = 0.01). CONCLUSIONS Our findings suggest that increasing light-intensity activities, especially HLPA, may be a viable approach to reducing the rate of physical function decline in individuals who are unable or reluctant to initiate or maintain adequate levels of moderate-intensity activities.

Risk of adult acute and chronic myeloid leukemia with cigarette smoking and cessation

BACKGROUND Cigarette smoking is an established risk factor for adult myeloid leukemia, particularly acute myeloid leukemia (AML), but less is known about the nature of this association and effects of smoking cessation on risk. METHODS In a large population-based case-control study of myeloid leukemia that included 414 AML and 185 chronic myeloid leukemia (CML) cases and 692 controls ages 20-79 years, we evaluated risk associated with cigarette smoking and smoking cessation using unconditional logistic regression methods and cubic spline modeling. RESULTS AML and CML risk increased with increasing cigarette smoking intensity in men and women. A monotonic decrease in AML risk was observed with increasing time since quitting, whereas for CML, the risk reduction was more gradual. For both AML and CML, among long-term quitters (≥30 years), risk was comparable to non-smokers. CONCLUSIONS Our study confirms the increased risk of myeloid leukemia with cigarette smoking and provides encouraging evidence of risk attenuation following cessation.

Comparability and Representativeness of Control Groups in a Case-Control Study of Infant Leukemia: A Report From the Children's Oncology Group

Traditionally, controls in US pediatric cancer studies were selected through random digit dialing. With declining participation and lack of nonparticipant information, random digit dialing (RDD) controls may be substandard. Birth certificate (BC) controls are an alternative, because they are population based and include data from nonparticipants. The authors examined controls collected by random digit dialing and birth certificates for a Childrens Oncology Group case-control study of infant leukemia in 1995-2006. Demographic variables were used to assess differences in RDD and BC controls and their representativeness. RDD and BC controls did not differ significantly with regard to maternal variables (age, race, education, marital status, alcohol during pregnancy) or child variables (sex, gestational age, birth weight), but they varied in smoking during pregnancy (22% RDD controls, 12% BC controls) (P = 0.05). The studys combined control group differed significantly from US births: Mothers of controls were more likely to be older (29.8 vs. 27.2 years), white (84% vs. 59%), and married (85% vs. 67%) and to have >16 years of education (37% vs. 25%). Control children were more often full term (88% vs. 81%) and heavier (3,436 vs. 3,317 g). Finally, participating BC mothers were likely to be older and to have more education than nonparticipants. Thus, the studys control groups were comparable but differed from the population of interest.