Victor Kamensky

Adherence to cancer prevention guidelines and cancer incidence, cancer mortality, and total mortality: a prospective cohort study

BACKGROUND Several health agencies have issued guidelines promoting behaviors to reduce chronic disease risk; however, little is known about the impact of such guidelines, particularly on cancer incidence. OBJECTIVE The objective was to determine whether greater adherence to the American Cancer Society (ACS) cancer prevention guidelines is associated with a reduction in cancer incidence, cancer mortality, and total mortality. DESIGN The NIH-AARP Diet and Health Study, a prospective cohort study of 566,401 adults aged 50-71 y at recruitment in 1995-1996, was followed for a median of 10.5 y for cancer incidence, 12.6 y for cancer mortality, and 13.6 y for total mortality. Participants who reported a history of cancer or who had missing data were excluded, yielding 476,396 subjects for analysis. We constructed a 5-level score measuring adherence to ACS guidelines, which included baseline body mass index, physical activity, alcohol intake, and several aspects of diet. Cox proportional hazards models were used to compute HRs and 95% CIs for the association of the adherence score with cancer incidence, cancer mortality, and total mortality. All analyses included fine adjustment for cigarette smoking. RESULTS Among 476,396 participants, 73,784 incident first cancers, 16,193 cancer deaths, and 81,433 deaths from all causes were identified in the cohort. Adherence to ACS guidelines was associated with reduced risk of all cancers combined: HRs (95% CIs) for the highest compared with the lowest level of adherence were 0.90 (0.87, 0.93) in men and 0.81 (0.77, 0.84) in women. Fourteen of 25 specific cancer sites showed a reduction in risk associated with increased adherence. Adherence was also associated with reduced cancer mortality [HRs (95% CIs) were 0.75 (0.70, 0.80) in men and 0.76 (0.70, 0.83) in women] and reduced all-cause mortality [HRs (95% CIs) were 0.74 (0.72, 0.76) in men and 0.67 (0.65, 0.70) in women]. CONCLUSIONS In both men and women, adherence to the ACS guidelines was associated with reductions in all-cancer incidence and the incidence of cancer at specific sites, as well as with reductions in cancer mortality and total mortality. These data suggest that, after accounting for cigarette smoking, adherence to a set of healthy behaviors may have considerable health benefits.

Adult height in relation to risk of cancer in a cohort of Canadian women.

Although the influence of body mass index on cancer risk has been intensively investigated, few epidemiologic studies have examined the association of adult height with risk of cancer. We assessed the association of height with risk of all cancer and of 19 site‐specific cancers in the Canadian National Breast Screening Study, a prospective cohort of nearly 90,000 women. Weight and height were measured at enrollment, and information on reproductive and medical history as well as lifestyle exposures was obtained by means of questionnaire. After exclusions, 5,679 incident invasive cancers were identified among 88,256 women. We used Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) per 10 cm increase in height. All tests of statistical significance were two sided. All cancers combined and ten specific sites (colorectum, colon, premenopausal breast, postmenopausal breast, endometrium, ovary, kidney, thyroid, melanoma and leukemia) showed statistically significant positive associations with height. The HR for all cancers combined was 1.13 (95% CI: 1.08–1.18), and the magnitude of the associations for specific sites ranged from HR 1.11 (95% CI: 1.03–1.20) for postmenopausal breast cancer to HR 1.51 (95% CI: 1.27–1.80) for melanoma. Our study provides strong support for a positive association of adult height with risk of certain cancers. The underlying biological mechanisms are not clear but may differ by anatomic site.

Adult Stature and Risk of Cancer at Different Anatomic Sites in a Cohort of Postmenopausal Women

Background: Prospective studies in Western and Asian populations suggest that height is a risk factor for various cancers. However, few studies have explored potential confounding or effect modification of the association by other factors. Methods: We examined the association between height measured at enrollment in 144,701 women participating in the Womens Health Initiative and risk of all cancers combined and cancer at 19 specific sites. Over a median follow-up of 12.0 years, 20,928 incident cancers were identified. We used Cox proportional hazards models to estimate HR and 95% confidence intervals (CI) per 10 cm increase in height, with adjustment for established risk factors. We also examined potential effect modification of the association with all cancer and specific cancers. Results: Height was significantly positively associated with risk of all cancers (HR = 1.13; 95% CI, 1.11–1.16), as well as with cancers of the thyroid, rectum, kidney, endometrium, colorectum, colon, ovary, and breast, and with multiple myeloma and melanoma (range of HRs: 1.13 for breast cancer to 1.29 for multiple myeloma and thyroid cancer). These associations were generally insensitive to adjustment for confounders, and there was little evidence of effect modification. Conclusions: This study confirms the positive association of height with risk of all cancers and a substantial number of cancer sites. Impact: Identification of single-nucleotide polymorphisms associated both with height and with increased cancer risk may help elucidate the association. Cancer Epidemiol Biomarkers Prev; 22(8); 1353–63. ©2013 AACR.

Body Fat and Breast Cancer Risk in Postmenopausal Women: A Longitudinal Study

Associations between anthropometric indices of obesity and breast cancer risk may fail to capture the true relationship between excess body fat and risk. We used dual-energy-X-ray-absorptiometry- (DXA-) derived measures of body fat obtained in the Womens Health Initiative to examine the association between body fat and breast cancer risk; we compared these risk estimates with those for conventional anthropometric measurements. The study included 10,960 postmenopausal women aged 50–79 years at recruitment, with baseline DXA measurements and no history of breast cancer. During followup (median: 12.9 years), 503 incident breast cancer cases were diagnosed. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. All baseline DXA-derived body fat measures showed strong positive associations with breast cancer risk. The multivariable-adjusted HR for the uppermost quintile level (versus lowest) ranged from 1.53 (95% CI 1.14–2.07) for fat mass of the right leg to 2.05 (1.50–2.79) for fat mass of the trunk. Anthropometric indices (categorized by quintiles) of obesity (BMI (1.97, 1.45–2.68), waist circumference (1.97, 1.46–2.65), and waist : hip ratio (1.91, 1.41–2.58)) were all strongly, positively associated with risk and did not differ from DXA-derived measures in prediction of risk.

Potassium Intake and Risk of Stroke in Women With Hypertension and Nonhypertension in the Women’s Health Initiative

Background and Purpose— Dietary potassium has been associated with lower risk of stroke, but there are little data on dietary potassium effects on different stroke subtypes or in older women with hypertension and nonhypertension. Methods— The study population consisted of 90 137 postmenopausal women aged 50 to 79 at enrollment, free of stroke history at baseline, followed up prospectively for an average of 11 years. Outcome variables were total, ischemic, and hemorrhagic stroke, and all-cause mortality. Incidence was compared across quartiles of dietary potassium intake, and hazard ratios were obtained from Cox proportional hazards models after adjusting for potential confounding variables, and in women with hypertension and nonhypertension separately. Results— Mean dietary potassium intake was 2611 mg/d. Highest quartile of potassium intake was associated with lower incidence of ischemic and hemorrhagic stroke and total mortality. Multivariate analyses comparing highest to lowest quartile of potassium intake indicated a hazard ratio of 0.90 (95% confidence interval, 0.85–0.95) for all-cause mortality, 0.88 (95% confidence interval, 0.79–0.98) for all stroke, and 0.84 (95% confidence interval, 0.74–0.96) for ischemic stroke. The effect on ischemic stroke was more apparent in women with nonhypertension among whom there was a 27% lower risk with hazard ratio of 0.73 (95% confidence interval, 0.60–0.88), interaction P<0.10. There was no association with hemorrhagic stroke. Conclusions— High potassium intake is associated with a lower risk of all stroke and ischemic stroke, as well as all-cause mortality in older women, particularly those who are not hypertensive.

Transmission/disequilibrium tests of androgen receptor and glutathione S-transferase pi variants in prostate cancer families.

Population‐based case‐control studies have found relationships between risk of prostate cancer and genetic polymorphisms in the CAG repeat and GGC repeat of the X‐linked androgen receptor gene (AR) as well as the autosomal gene coding for glutathione S‐transferase pi (GSTP1). This family‐based study utilized the transmission disequilibrium test to examine whether there was evidence that these polymorphisms could account for familial aggregation of prostate cancer. Seventy‐nine North American pedigrees were studied. Most of these families had 3 or more affected first‐degree relatives. Genotype information was obtained on 578 individuals. The reconstruction combined transmission disequilibrium test (RC‐TDT) was used to test for linkage. There was no evidence of linkage to the CAG and GGC repeat sequences in the AR gene or the pentanucleotide (ATAAA) repeat in the GSTP1 gene when each allele was analyzed separately or when alleles were grouped by repeat length. Our findings do not support the hypothesis that familial clustering of prostate cancer in high‐risk families is attributable to these genetic variants.

Combined conjugated esterified estrogen plus methyltestosterone supplementation and risk of breast cancer in postmenopausal women

OBJECTIVES Testosterone supplementation is being prescribed increasingly to treat symptoms of hormone deficiency in pre- and postmenopausal women; however, studies of the association of testosterone therapy, alone or in combination with estrogen, with risk of breast cancer are limited. The current study assessed the association of combination conjugated esterified estrogen and methyltestosterone (CEE+MT) use and breast cancer risk in postmenopausal women in the Womens Health Initiative (WHI). STUDY DESIGN At Year 3 of follow-up, women in the WHI observational study (N=71,964) provided information on CEE+MT use in the past two years, duration of use, and the brand name of the product. In addition, in each of years 4-8, women were asked whether they had used CEE+MT in the previous year. After 10 years of follow-up, 2832 incident breast cancer cases were identified. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association of CEE+MT use (irrespective of use of other hormones) and of exclusive CEE+MT use in relation to breast cancer risk. RESULTS Neither CEE+MT use nor exclusive use of CEE+MT was associated with risk: multivariable-adjusted HR 1.06, 95% CI 0.82-1.36 and HR 1.22, 95% CI 0.78-1.92, respectively. Among women with a natural menopause, the HR for exclusive use was 1.32 (95% CI 0.68-2.55). There was no indication of an association when repeated measures of CEE+MT use were included in a time-dependent covariates analysis. CONCLUSION The present study, the largest prospective study to date, did not show a significant association of CEE+MT supplementation and risk of breast cancer.

Association of Hemoglobin Concentration With Total and Cause-Specific Mortality in a Cohort of Postmenopausal Women

Anemia and low and high levels of hemoglobin have been associated with increased mortality and morbidity. However, most studies have measured hemoglobin at only 1 time point, and few studies have considered possible reverse causation. We used data from the Womens Health Initiative, in which baseline hemoglobin was measured in 160,081 postmenopausal women and year 3 hemoglobin was measured in 75,658 participants, to examine the associations of hemoglobin concentration with total mortality, coronary heart disease mortality, and cancer mortality. Women were enrolled from 1993 to 1998 and followed for a median of 16 years. Cox proportional hazards models were used to estimate the relative mortality hazards associated with deciles of baseline hemoglobin and the mean of baseline + year 3 hemoglobin. Both low and high deciles of baseline hemoglobin were positively associated with all 3 outcomes in the total cohort. In analyses restricted to women with 2 measurements, a low mean hemoglobin level was robustly and positively associated with all 3 outcomes, after exclusion of the early years of follow-up. High mean hemoglobin was also associated with increased risk of total mortality, whereas associations with heart disease mortality and cancer mortality were weaker and inconsistent. Our results provide evidence that low and high levels of hemoglobin are associated with increased risk of mortality in otherwise healthy women.

Reproductive factors, exogenous hormone use, and risk of pancreatic cancer in postmenopausal women

INTRODUCTION The epidemiologic literature on menstrual and reproductive factors associated with pancreatic cancer has yielded weak and inconsistent evidence of an association. Furthermore, few cohort studies have examined the association of exogenous hormone use, including type and duration, with this disease. The aim of this study was to assess the association of these exposures with risk of pancreatic cancer in a large cohort of postmenopausal women. METHODS We used data from the Womens Health Initiative on 1003 cases of pancreatic cancer diagnosed among 158,298 participants over 14.3 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations of interest. RESULTS Being parous vs. nulliparous was associated with reduced risk (HR=0.84, 95% CI 0.70-1.00), and women who had 1-2 and 3-4 births were at decreased risk compared to nulliparous women, whereas women who had >5 births showed no decrease in risk. Compared to women who gave birth between the ages of 20-29, women who gave birth at age 30 or above were at increased risk (HR 1.23, 95% CI 1.00-1.53, p for trend 0.003). Other reproductive factors and exogenous hormone use were not associated with risk. CONCLUSIONS Together with the existing literature on this topic, our results suggest that reproductive and hormonal exposures are unlikely to play an important role in the etiology of pancreatic cancer.