History of diabetes mellitus and subsequent prostate cancer risk in the NIH-AARP Diet and Health Study

Objective A history of diabetes has been hypothesized to decrease prostate cancer risk, but studies have not always considered confounding or effect modification by dietary or lifestyle factors. Methods We examined the association between diabetes history and subsequent prostate cancer risk in 328,316 men enrolled in the NIH-AARP Diet and Health Study. Participants were ages 50–71 years and without a prostate cancer diagnosis at baseline in 1995. A prior history of physician-diagnosed diabetes was assessed using a self-administered mailed questionnaire. Cases of prostate cancer were ascertained by matching the cohort to state cancer registries. Multivariable relative risks (RR) and 95% confidence intervals (CI) of prostate cancer were estimated using Cox regression. Results During 5 years and 1,432,676 person-years of follow-up, 11,193 prostate cancer cases were ascertained. The age-adjusted and multivariable RRs of prostate cancer comparing men with diabetes to those without diabetes were 0.69 (95% CI = 0.64, 0.74) and 0.71 (95% CI = 0.66, 0.76), respectively, indicating no important confounding. The inverse association between diabetes and prostate cancer was particularly strong among men in the highest category of routine physical activity at work or home (RR = 0.41; 95% CI = 0.23, 0.74; p value for test of interaction = 0.03). Findings were similar for organ-confined and advanced prostate cancer. Conclusion Results from this large prospective study suggest that a history of diabetes is associated with a decreased risk of prostate cancer. The relationship strengthened with high levels of routine physical activity. Because increased physical activity is associated with lower circulating levels of insulin and testosterone, our findings support a role of hypoinsulinemia and low androgenicity linking diabetes to decreased prostate cancer risk.     

Sugars in diet and risk of cancer in the NIH-AARP Diet and Health Study

Prospective epidemiologic data on the effects of different types of dietary sugars on cancer incidence have been limited. In this report, we investigated the association of total sugars, sucrose, fructose, added sugars, added sucrose and added fructose in the diet with risk of 24 malignancies. Participants (n = 435,674) aged 50-71 years from the NIH-AARP Diet and Health Study were followed for 7.2 years. The intake of individual sugars was assessed using a 124-item food frequency questionnaire (FFQ). Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) in multivariable models adjusted for confounding factors pertinent to individual cancers. We identified 29,099 cancer cases in men and 13,355 cases in women. In gender-combined analyses, added sugars were positively associated with risk of esophageal adenocarcinoma (HR(Q5 vs. Q1) : 1.62, 95% CI: 1.07-2.45; p(trend) = 0.01), added fructose was associated with risk of small intestine cancer (HR(Q5 vs. Q1) : 2.20, 95% CI: 1.16-4.16; p(trend) = 0.009) and all investigated sugars were associated with increased risk of pleural cancer. In women, all investigated sugars were inversely associated with ovarian cancer. We found no association between dietary sugars and risk of colorectal or any other major cancer. Measurement error in FFQ-reported dietary sugars may have limited our ability to obtain more conclusive findings. Statistically significant associations observed for the rare cancers are of interest and warrant further investigation.     

Alcohol intake and risk of thyroid cancer in the NIH-AARP Diet and Health Study

Background:

Certain studies suggest that alcohol may reduce the risk of thyroid cancer in women, but the effect in men remains unclear.

Methods:

We analysed the association between alcohol and thyroid cancer in a large (n=490 159) prospective NIH-AARP Diet and Health Study with self-reported beer, wine, and liquor intakes.

Results:

Over 7.5 years of follow-up (median), 170 men and 200 women developed thyroid cancer. Overall, the thyroid cancer risk decreased with greater alcohol consumption (⩾2 drinks per day vs none, relative risk=0.57, 95% CI 0.36–0.89, P-trend=0.01).

Conclusions:

These results suggest a potential protective role for alcohol consumption in thyroid cancer.     

Ovarian cancer risk factors by histologic subtypes in the NIH-AARP Diet and Health Study

Data suggest that risk factors for ovarian carcinoma vary by histologic type, but findings are inconsistent. We prospectively evaluated risk factors by histological subtypes of incident ovarian cancer (n = 849) in a cohort of 169,391 women in the NIH-AARP Diet and Health Study. We constructed Cox models of individual exposures by comparing case subtypes to the entire non-case group and assessed p-heterogeneity in case-case comparisons using serous as the reference category. Substantial risk differences between histologic subtypes were observed for menopausal hormone therapy (MHT) use, oral contraceptive (OC) use, parity and body mass index (p-heterogeneity = 0.01, 0.03, 0.05, 0.03, respectively). MHT users were at increased risk for all histologic subtypes except for mucinous carcinomas, where risk was reduced (relative risk (RR) = 0.37; 95% confidence interval (CI): 0.18, 0.80). OC users were only at significantly decreased risk for serous cancers (RR = 0.69; 95% CI: 0.55, 0.85). Although parity was inversely associated with risk of all subtypes, the RRs ranged from 0.28 (clear cell) to 0.83 (serous). Obesity was a significant risk factor only for endometrioid cancers (RR = 1.64; 95% CI: 1.00, 2.70). Our findings support a link between etiological factors and histological heterogeneity in ovarian carcinoma.     

Adolescent animal product intake in relation to later prostate cancer risk and mortality in the NIH-AARP Diet and Health Study

Background Adolescent intake of animal products has been proposed to contribute to prostate cancer (PCa) development because of its potentially carcinogenic constituents and influence on hormone levels during adolescence.Methods We used data from 159,482 participants in the NIH-AARP Diet and Health Study to investigate associations for recalled adolescent intake of red meat (unprocessed beef and processed red meat), poultry, egg, canned tuna, animal fat and animal protein at ages 12–13 years with subsequent PCa risk and mortality over 14 years of follow-up. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of total (n = 17,349), advanced (n = 2,297) and fatal (n = 804) PCa.Results Suggestive inverse trends were observed for adolescent unprocessed beef intake with risks of total, advanced and fatal PCa (multivariable-adjusted P-trends = 0.01, 0.02 and 0.04, respectively). No consistent patterns of association were observed for other animal products by PCa outcome.Conclusion We found evidence to suggest that adolescent unprocessed beef intake, or possibly a correlate of beef intake, such as early-life socioeconomic status, may be associated with reduced risk and mortality from PCa. Additional studies with further early-life exposure information are warranted to better understand this association.Subject terms: Epidemiology, Risk factors     

Dietary fat intake and risk of ovarian cancer in the NIH-AARP Diet and Health Study

Background:

Fat intake has been postulated to increase risk of ovarian cancer, but previous studies have reported inconsistent results.

Methods:

The NIH-AARP Diet and Health Study, a large prospective cohort, assessed diet using a food frequency questionnaire at baseline in 1995–1996. During an average of 9 years of follow-up, 695 ovarian cancer cases were ascertained through the state cancer registry database. The relative risks (RRs) and 95% confidence interval (CI) were estimated using a Cox proportional hazard model.

Results:

Women in the highest vs the lowest quintile of total fat intake had a 28% increased risk of ovarian cancer (RR_{Q5 vs Q1}=1.28, 95% CI: 1.01–1.63). Fat intake from animal sources (RR_{Q5 vs Q1}=1.30; 95% CI: 1.02–1.66), but not from plant sources, was positively associated with ovarian cancer risk. Saturated and monounsaturated fat intakes were not related to risk of ovarian cancer, but polyunsaturated fat intake showed a weak positive association. The association between total fat intake and ovarian cancer was stronger in women who were nulliparous or never used oral contraceptives.

Conclusion:

Fat intake, especially from animal sources, was related to an increased risk of ovarian cancer. The association may be modified by parity and oral contraceptive use, which warrants further investigation.     

Breast cancer risk in older women: results from the NIH-AARP Diet and Health Study

Background

Divergent risk factors exist for premenopausal and postmenopausal breast cancers, but it is unclear whether differences by age exist among postmenopausal women.

Methods

We examined relationships among 190,872 postmenopausal women, ages 50–71 years recruited during 1995–1996 for the NIH-AARP Diet and Health Study, in whom 7,384 incident invasive breast carcinomas were identified through 2006. Multivariable Cox regression hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated for breast cancer risk factors by age (50–59, 60–69, ≥70 years).

Results

The only factor showing significant statistical heterogeneity by age (p _het = 0.001) was menopausal hormone therapy duration, but trends were apparent across all ages and the strongest association prevailed among women 60–69 years. Although other risk factors did not show statistically significant heterogeneity by age, we did observe attenuated relations for parity and late age at first birth among older women [e.g., HR for age at first birth ≥30 vs. 20–24 = 1.62 (95 % CI 1.23–2.14) for women 50–59 years vs. 1.12 (0.96–1.31) for ≥70 years]. In contrast, risk estimates associated with alcohol consumption and BMI tended to be slightly stronger among the oldest subjects [e.g., HR for BMI ≥35 vs. 18.5–24.9 = 1.24 (95 % CI 0.97–1.58) for 50–59 years vs. 1.46 (1.26–1.70) for ≥70 years]. These differences were somewhat more pronounced for estrogen receptor positive and ductal cancers, tumors predominating among older women. Breast cancer family history, physical activity, and previous breast biopsies did not show divergent associations by age.

Conclusion

Although breast cancer risk factor differences among older women were not large, they may merit further consideration with respect to individualized risk prediction.     

Coffee consumption and the risk of prostate cancer: the Ohsaki Cohort Study

Background:

Epidemiological evidence regarding the effect of coffee on the incidence of prostate cancer is inconsistent. We aimed to investigate coffee consumption and the risk of prostate cancer risk in a general Japanese population.

Methods:

We conducted a prospective cohort study in Ohsaki city, Japan, where 18 853 men aged 40–79 years participated in a baseline survey. Coffee consumption was assessed via a validated self-administered questionnaire. During 11 years of follow-up (from January 1 1995 to December 31, 2005), 318 incident cases of prostate cancer were detected. The Cox proportional hazards regression model was used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs).

Results:

There was a significant inverse association between coffee consumption and the incidence risk of prostate cancer. Compared with those who did not drink coffee, the multivariate adjusted HRs were 0.81 (95% CI: 0.61–1.07), 0.73 (95% CI: 0.53–1.00), and 0.63 (095% CI: 0.39–1.00) for those who drank coffee occasionally, 1–2 cups per day, and ⩾3 cups per day, respectively, with a P for trend of 0.02.

Conclusion:

This prospective finding from a Japanese population adds evidence that coffee intake is inversely associated with the incidence of prostate cancer.     

Coffee consumption and risk of localized,advanced and fatal prostate cancer: a population-based prospective study

BackgroundThe epidemiological evidence on possible relationships between coffee consumption and prostate cancer (PCa) risk by subtype of the disease (localized, advanced) and fatal PCa risk is limited.Materials and methodsA population-based cohort of 44 613 Swedish men aged 45–79 years was followed up from January 1998 through December 2010 for incidence of localized (n = 2368), advanced (n = 918) and fatal (n = 515) PCa. We assessed the associations between coffee consumption and localized, advanced and fatal PCa risk using competing-risk regressions. We examined possible effect modification by body mass index (BMI).ResultsFor localized PCa, each one cup increase in daily coffee consumption was associated with a 3% reduced risk [sub-hazard ratio (SHR) = 0.97, 95% confidence interval (CI) = 0.95–0.99]. For advanced and fatal PCa, we found a non-significant inverse association; each one cup increase was associated with a 2% reduced risk of advanced [SHR (95% CI) = 0.98 (0.95–1.02)] and fatal PCa [SHR (95% CI) = 0.98 (0.93–1.03)]. We observed evidence of effect modification by BMI for localized PCa (P_interaction = 0.03); the inverse association was stronger among overweight and obese men (BMI ≥ 25 kg/m²) compared with normal-weight men (BMI < 25 kg/m²).ConclusionsWe observed a clear inverse association between coffee consumption and risk of localized PCa, especially among overweight and obese men.     

Dietary fiber and grain consumption in relation to head and neck cancer in the NIH-AARP Diet and Health Study

Background  

Dietary fiber and grain consumption may reduce the risk of head and neck cancer; however, the epidemiological evidence is limited. We investigated this relationship in the National Institutes of Health (NIH)-AARP Diet and Health Study.     

Coffee consumption and prostate cancer risk: an updated meta-analysis

Purpose

Many epidemiological studies have been conducted to explore the association between coffee consumption and prostate cancer. However, the results remain inconsistent. We performed a large meta-analysis of relevant studies to derive a more precise estimation of this relationship.

Methods

Systematic searches of PubMed and several other databases up to June 2013 were retrieved. All epidemiologic studies regarding coffee consumption and prostate cancer risk were included, and odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to estimate the strength of the association.

Results

Twelve case–control studies involving 7,909 prostate cancer cases and 9,461 controls and nine cohort studies involving 455,123 subjects were included in our analysis. Compared with the lowest category, the unstratified highest category of coffee consumption showed a significance reduction in prostate cancer risk of a fixed-effects model (OR 0.91, CI 0.86–0.97). A borderline significant influence was also found when the stratified highest category (US ≥4, Europe ≥5) of coffee consumption was compared with the reference category (OR 0.96, CI 0.92–1.00), but no relationships were observed for the other two categories. In another analysis conducted by coffee consumption and prostate cancer stage and Gleason grade, our results showed a significant inverse association in all categories of prostate cancer except Gleason <7 grade in a fixed-effects model; the results remained the same, except for advanced prostate cancer, in a random-effects model.

Conclusions

Our meta-analysis suggests that high (e.g., highest ≥4 or 5 cups/day) coffee consumption may not only be associated with a reduced risk of overall prostate cancer, but also inversely associated with fatal and high-grade prostate cancer.     

Attained height,sex, and risk of cancer at different anatomic sites in the NIH-AARP Diet and Health Study

Purpose

To examine the association of adult height with risk of cancer at different anatomic sites in a cohort of men and women.

Methods

The association of self-reported height with subsequent cancer risk was assessed in 288,683 men and 192,514 women enrolled in the National Institutes of Health-AARP Diet and Health Study. After a median follow-up of 10.5 years, incident cancer was diagnosed in 51,139 men and 23,407 women. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) for the association of height with cancer risk.

Results

After adjustment for covariates, height was positively associated with increased risk of all cancers combined in both men [HR_{10 cm increase} = 1.05 (95 % CI 1.04–1.06)] and women [HR_{10 cm increase} = 1.08 (95 % CI 1.06–1.10)]. Several sites common to men and women showed significant positive associations with height: colon, rectum, kidney, melanoma, and non-Hodgkin’s lymphoma. For other shared sites, the association differed by sex. For still other sites, there was no clear association with height. Positive associations were also observed with cancers of the breast, endometrium, and prostate.

Conclusions

Different patterns were observed in the height–cancer association by sex. Studies investigating the biological mechanisms underlying the association of height with cancer risk should focus on those sites that show a reproducible association with attained height.     

Physical activity, sedentary behavior, and the risk of colon and rectal cancer in the NIH-AARP Diet and Health Study

Objective  In order to prospectively investigate physical activity at varying intensities and sedentary behavior in relation to colorectal cancer. Methods  We considered 488,720 participants of the NIH-AARP Diet and Health Study who were aged 50–71 years at baseline in 1995–1996. Through 31 December, 2003, we identified 3,240 and 1,482 colorectal cancers among men and women, respectively. We estimated multivariable relative risks (RR) and 95% confidence intervals (CI) of colorectal cancer using Cox regression. Results  Engaging in exercise/sports five or more times per week compared to never or rarely exercising was associated with a reduced risk of colon cancer among men (p = 0.001; RR = 0.79, 95% CI = 0.68–0.91) and a suggestive decrease in risk among women (p = 0.376; RR = 0.85, 95% CI = 0.70–1.04). Engaging in exercise/sports was also associated with a decreased risk of rectal cancer in men (P = 0.074; RR comparing extreme categories = 0.76, 95% CI = 0.61–0.94). In men, we observed inverse relations of both low intensity (p = 0.017; RR = 0.81, 95% CI = 0.65–1.00 for ≥7 h/week) and moderate to vigorous intensity activity (p = 0.037; RR = 0.82, 95% CI = 0.67–0.99 for ≥7 h/week) to colon cancer risk. In contrast, sedentary behavior (time spent watching television/videos) was positively associated with colon cancer (p < 0.001; RR = 1.61, 95% CI = 1.14–2.27 for ≥9 h/day) among men. Similar, but less pronounced relations were observed in women. Conclusion  Engaging in physical activity of any intensity is associated with reductions in colon and rectal cancer risk. Conversely, time spent sedentary is associated with increased colon cancer risk.     

Body fat distribution, weight change during adulthood, and thyroid cancer risk in the NIH-AARP Diet and Health Study

Body mass index (BMI) has been positively associated with thyroid cancer risk in several studies, but the underlying mechanisms remain unclear. We examined the associations for waist and hip circumference and weight change during adulthood with thyroid cancer risk among 125,347 men and 72,363 women in the NIH-AARP Diet and Health Study who completed a second mailed questionnaire in 1996-1997. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated separately by sex and adjusted for race/ethnicity, education and smoking status. During follow-up (median = 10.1 years), 106 men and 105 women were diagnosed with a first primary thyroid cancer, as identified through linkage to state cancer registries. Having a large waist circumference (above the clinical cutpoint for normal: > 102 cm in men and > 88 cm in women) was associated with increased risk in both men (HR = 1.79, 95% CI: 1.21-2.63) and women (HR = 1.54, 95% CI: 1.05-2.26). Having both a large waist and BMI in the obese range (≥ 30 kg/m2) approximately doubled the risk of thyroid cancer (HR in men = 2.13, 95% CI: 1.18-3.85; HR in women = 1.91, 95% CI: 1.31-3.25) compared to having a normal waist circumference/normal BMI (18.5-24.9 kg/m2). We also observed positive association for weight gain between ages 18-35 in men (gained ≥ 10.0 kg vs. lost/gained < 5 kg, HR = 1.49, 95% CI: 0.93-2.39, p-trend = 0.03), but the association was less pronounced in women. No clear association for weight gain in later life was observed. These results support a potential role for hormonal and metabolic parameters common to central adiposity in thyroid carcinogenesis.     

Coffee intake and breast cancer risk in the NIH-AARP diet and health study cohort

There are several biologic mechanisms whereby coffee might reduce breast cancer risk. Caffeine and caffeic acid, major coffee constituents, have been shown to suppress mammary tumor formation in animal models and to inhibit DNA methylation in human breast cancer cells, respectively. Coffee may also reduce risk through decreasing inflammation and influencing estrogen metabolism. However, epidemiologic studies have been inconsistent and few studies have examined the association by estrogen and progesterone receptor (ER/PR) status. We evaluated coffee intake for its effect on incident breast cancer in the National Institutes of Health-AARP Diet and Health Study cohort, which included 198,404 women aged 50-71 with no history of cancer, who in 1995-1996 completed a questionnaire capturing usual coffee intake over the past year. State cancer registry and mortality index linkage identified 9,915 primary incident breast carcinomas through December 2006; available information on hormone receptor (HR) status identified 2,051 ER+/PR+ and 453 ER-/PR- cancers. In multivariable proportional hazards models, coffee intake was not associated with breast cancer risk (p-value for trend = 0.38; relative risk = 0.98, 95% confidence interval: 0.91-1.07, for four or more cups per day as compared to women who never drank coffee), and results did not vary by body mass index or history of benign breast biopsy (p-value for interaction > 0.10). We found no evidence of a relationship with either caffeinated or decaffeinated coffee. Null findings persisted for risk of both HR-positive and -negative breast cancers. These findings from a large prospective cohort do not support a role of coffee intake in breast carcinogenesis.     

Coffee consumption and bladder cancer risk

The relationship between coffee drinking and the risk of bladder cancer was analyzed within the framework of a French hospital-based case-control study conducted between 1984 and 1987, which included 690 cases of histologically confirmed bladder cancer (599 males and 91 females), and 690 age-, sex- and hospital-matched controls. To dissociate the effects of smoking and coffee drinking among males, the analysis of the male group was restricted to 2 contrasted subgroups: non-smokers on the one hand, and current smokers and inhalers of black tobacco cigarettes on the other. Coffee drinking was found to be significantly associated with the risk of bladder cancer among men in both groups and the increase in the risk was dose-dependent (OR = 1, 2.9, 5.1 respectively, for drinking 1, 2, greater than or equal to 3 cups of coffee per day among non-smokers, and 1, 2.5 and 3.0 respectively, for drinking 1-4, 5-7, greater than cups among smokers). This result was not observed for women.     

Intensity and timing of physical activity in relation to postmenopausal breast cancer risk: the prospective NIH-AARP Diet and Health Study

Background  

Despite strong evidence of an inverse association of physical activity with postmenopausal breast cancer risk, whether a certain intensity or time of life of physical activity is most effective for lowering breast cancer risk is not known.