Crystal N. Holick

Physical Activity and Survival after Diagnosis of Invasive Breast Cancer

Previous studies suggest that increased physical activity may lower the risk of breast cancer incidence, but less is known about whether levels of physical activity after breast cancer diagnosis can influence survival. We prospectively examined the relation between postdiagnosis recreational physical activity and risk of breast cancer death in women who had a previous invasive breast cancer diagnosed between 1988 and 2001 (at ages 20-79 years). All women completed a questionnaire on recent postdiagnosis physical activity and other lifestyle factors. Among 4,482 women without history of recurrence at the time of completing the questionnaire, 109 died from breast cancer within 6 years of enrollment. Physical activity was expressed as metabolic equivalent task-hours per week (MET-h/wk); hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression. After adjusting for age at diagnosis, stage of disease, state of residence, interval between diagnosis and physical activity assessment, body mass index, menopausal status, hormone therapy use, energy intake, education, family history of breast cancer, and treatment modality compared with women expending <2.8 MET-h/wk in physical activity, women who engaged in greater levels of activity had a significantly lower risk of dying from breast cancer (HR, 0.65; 95% CI, 0.39-1.08 for 2.8-7.9 MET-h/wk; HR, 0.59; 95% CI, 0.35-1.01 for 8.0-20.9 MET-h/wk; and HR, 0.51; 95% CI, 0.29-0.89 for ≥21.0 MET-h/wk; P for trend = 0.05). Results were similar for overall survival (HR, 0.44; 95% CI, 0.32-0.60 for ≥21.0 versus <2.8 MET-h/wk; P for trend <0.001) and were similar regardless of a woman’s age, stage of disease, and body mass index. This study provides support for reduced overall mortality and mortality from breast cancer among women who engage in physical activity after breast cancer diagnosis. (Cancer Epidemiol Biomarkers Prev 2008;17(2):379–86)

Body mass index before and after breast cancer diagnosis: Associations with all-cause, breast cancer, and cardiovascular disease mortality

Background: Factors related to improving outcomes in breast cancer survivors are of increasing public health significance. We examined postdiagnosis weight change in relation to mortality risk in a cohort of breast cancer survivors. Methods: We analyzed data from a cohort of 3,993 women with ages 20 to 79 years living in New Hampshire, Massachusetts, or Wisconsin with invasive nonmetastatic breast cancers diagnosed in 1988 to 1999 identified through state registries. Participants completed a structured telephone interview 1 to 2 years after diagnosis and returned a mailed follow-up questionnaire in 1998 to 2001 that addressed postdiagnosis weight and other factors. Vital status information was obtained from the National Death Index through December 2005. Hazard ratios and 95% confidence intervals were estimated from Cox proportional hazards models and adjusted for prediagnosis weight, age, stage, smoking, physical activity, and other important covariates. Results: During an average 6.3 years of follow-up from the postdiagnosis questionnaire, we identified 421 total deaths, including 121 deaths from breast cancer and 95 deaths from cardiovascular disease. Increasing postdiagnosis weight gain and weight loss were each associated with greater all-cause mortality. Among women who gained weight after breast cancer diagnosis, each 5-kg gain was associated with a 12% increase in all-cause mortality (P = 0.004), a 13% increase in breast cancer–specific mortality (P = 0.01), and a 19% increase in cardiovascular disease mortality (P = 0.04). Associations with breast cancer mortality were not modified by prediagnosis menopausal status, cigarette smoking, or body mass index. Conclusion: These findings suggest that efforts to minimize weight gain after a breast cancer diagnosis may improve survival. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1403–9)

Diet after diagnosis and the risk of prostate cancer progression, recurrence, and death (United States).

Objectives We examined post-diagnostic diet and risk of cancer progression in a cohort of men with prostate cancer from the Health Professionals Follow-up Study.Methods We observed 392 progression outcomes among 1,202 men diagnosed with incident localized/regional prostate cancer between 1986 and 1996. Men completed prospective dietary surveys before and after diagnosis and were followed through 2000. We examined post-diagnostic consumption of red meat, grains, vegetables, fruits, milk, tomatoes, tomato sauce, and fish as predictors of progression using Cox proportional hazard regression models adjusted for total energy, age, clinical factors, and pre-diagnostic diet.Results Men in the highest versus lowest quartile of post-diagnostic fish consumption had a multivariate hazard ratio (HR) of progression of 0.73 (95% CI 0.52–1.02); the comparable HR for tomato sauce was 0.56 (95% CI 0.38–0.82). We observed inverse linear relationships for fish and tomato sauce and risk of progression (HR = 0.83, p-value = 0.006 and HR = 0.80, p-value = 0.04 for a two serving/week increase of fish and tomato sauce, respectively). Milk and fresh tomato consumption were associated with small elevations in risk.Conclusions These data suggest that diet after diagnosis may influence the clinical course of prostate cancer, and fish and tomato sauce may offer some protection against disease progression.

Comprehensive Association Analysis of the Vitamin D Pathway Genes, VDR, CYP27B1, and CYP24A1, in Prostate Cancer

Genetic variation in vitamin D–related genes has not been investigated comprehensively and findings are equivocal. We studied the association between polymorphisms across the entire vitamin D receptor (VDR) gene and genes encoding for vitamin D activating enzyme 1-α-hydroxylase (CYP27B1) and deactivating enzyme 24-hyroxylase (CYP24A1) and prostate cancer risk among middle-aged men using a population-based case-control study design. DNA samples and survey data were obtained from incident cases (n = 630), 40 to 64 years old, identified through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results cancer registry from 1993 to 1996 and from random controls (n = 565) of similar age without a history of prostate cancer. We selected and genotyped tag single-nucleotide polymorphisms to predict common variants across VDR (n = 22), CYP27B1 (n = 2), and CYP24A1 (n = 14). Haplotypes of VDR and CYP24A1 were not associated with prostate cancer risk. In the genotype analysis, homozygotes at two VDR loci (rs2107301 and rs2238135) were associated with a 2- to 2.5-fold higher risk of prostate cancer compared with the homozygote common allele [odds ratio, 2.47 (95% confidence interval, 1.52-4.00; P = 0.002) and 1.95 (95% confidence interval, 1.17-3.26; P = 0.007), respectively; P value corrected for multiple comparisons for VDR = 0.002]. We found no evidence that the two associated VDR single-nucleotide polymorphisms were modified by age at diagnosis, prostate cancer aggressiveness, first-degree family history of prostate cancer, or vitamin D intake. Genotypes of CYP27B1 and CYP24A1 were not associated with prostate cancer risk. Our findings suggest that polymorphisms in the VDR gene may be associated with prostate cancer risk and, therefore, that the vitamin D pathway might have an etiologic role in the development of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(10):1990–9)

Aspirin use and lung cancer in men

We examined prospectively the relation between regular aspirin use and lung cancer risk in the Health Professionals Follow-Up Study. Of 49 383 US men aged 40–75 years who completed biennial self-administered questionnaires that assessed aspirin use beginning in 1986, 328 developed lung cancer during 601 453 person-years of follow-up through 31 December 2000. No information on aspirin dose was available. Controlling for current age, smoking status, and age at starting to smoke regularly, the relative risk (RR) of total lung cancer for regular users of aspirin (twice or more per week) at baseline compared to nonusers was 1.13 (95% confidence interval (CI) =0.89–1.43). Results were similar for non-small-cell lung cancer (RR=1.16; 95% CI=0.88–1.54). No apparent dose-dependent association was observed for the frequency of aspirin use and lung cancer risk (P for trend=0.64), and results remained null when consistent use of aspirin over time was examined. These findings do not suggest that regular aspirin use is associated with a reduced lung cancer risk.

Coffee, Tea, Caffeine Intake, and Risk of Adult Glioma in Three Prospective Cohort Studies

Current data suggest that caffeinated beverages may be associated with lower risk of glioma. Caffeine has different effects on the brain, some of which could play a role in brain carcinogenesis, and coffee has been consistently associated with reduced risk of liver cancer, thus suggesting a potential anticarcinogenic effect. A total of 335 incident cases of gliomas (men, 133; women, 202) were available from three independent cohort studies. Dietary intake was assessed by food frequency questionnaires obtained at baseline and during follow-up. Cox proportional hazard models were used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI) between consumption of coffee, tea, carbonated beverages, caffeine, and glioma risk adjusting for age and total caloric intake. Estimates from each cohort were pooled using a random-effects model. Consumption of five or more cups of coffee and tea daily compared with no consumption was associated with a decrease risk of glioma (RR, 0.60; 95% CI, 0.41-0.87; Ptrend = 0.04). Inverse, although weaker, associations were also observed between coffee, caffeinated coffee, tea, and carbonated beverages and glioma risk. No association was observed between decaffeinated coffee and glioma risk. Among men, a statistically significant inverse association was observed between caffeine consumption and risk of glioma (RR, 0.46; 95% CI, 0.26-0.81; Ptrend = 0.03); the association was weaker among women. Our findings suggest that consumption of caffeinated beverages, including coffee and tea, may reduce the risk of adult glioma, but further research is warranted to confirm these findings in other populations. Cancer Epidemiol Biomakers Prev; 19(1);39–47

Prospective study of meat intake and dietary nitrates, nitrites, and nitrosamines and risk of adult glioma

BACKGROUND The hypothesis that nitrosamine exposure may increase the risk of glioma has been circulating for several decades, but testing it has been difficult because of the ubiquitous nature of nitrosamine exposure. Diet has been the focus of many studies because it can substantially influence nitrosamine exposure, mostly from the endogenous formation of nitrosamines based on intake of nitrite and nitrate. OBJECTIVE The objective was to examine the relation between intakes of meats, nitrate, nitrite, and 2 nitrosamines [nitrosodimethylamine (NDMA) and nitrosopyrolidine (NPYR)] and glioma risk in a prospective analysis. METHODS Data from 3 US prospective cohort studies were combined for this analysis; 335 glioma cases were diagnosed during < or =24 y of follow-up. Dietary intake was assessed with food-frequency questionnaires. Nitrate, nitrite, and nitrosamine values were calculated based on published values of these nutrients in various foods over different periods in time. Cox proportional hazards models were used to estimate incidence rate ratios (RRs) and 95% CIs. Estimates from each cohort were pooled by using a random-effects model. RESULTS Risk of glioma was not elevated among individuals in the highest intake category of total processed meats (RR: 0.92; 95% CI: 0.48, 1.77), nitrate (RR: 1.02; 95% CI: 0.66, 1.58), nitrites (RR: 1.26; 95% CI: 0.89, 1.79), or NDMA (RR: 0.88; 95% CI: 0.57, 1.36) compared with the lowest category. No effect modification was observed by intake of vitamins C or E or other antioxidant measures. CONCLUSION We found no suggestion that intake of meat, nitrate, nitrite, or nitrosamines is related to the risk of glioma.