Serum uric acid and risk of cancer mortality in a large prospective male cohort

Objective To examine the prognostic role of serum uric acid (SUA) for cancer mortality in apparently healthy men across a wide age range. Methods Prospective data from a large cohort of 83,683 male Austrian adults with a median follow-up of 13.6 years was analyzed. Cox proportional hazards models, adjusted for established risk factors, were calculated to evaluate SUA as a predictive marker for fatal cancer events. Results High SUA (>6.71 mg/dl) was independently associated with increased risk of mortality from all cancers, showing a clear dose–response relationship (p for trend < 0.0001); the adjusted hazard ratio for the highest versus lowest quintile of SUA was 1.41 (1.22–1.62). In subgroup analyses this hazard ratio increased to 1.53 (1.29–1.80) for participants aged <65 years. When considering the time interval between baseline SUA measurement and subsequent death, SUA levels were more predictive for “late deaths”, occurring 10 or more years after screening (HR 1.65 [1.35–2.03], p < 0.0001), in comparison to deaths within 10 years after SUA measurement. In cancer site-specific analyses, SUA was significantly associated with deaths from malignant neoplasms of digestive organs (p = 0.03) and respiratory system and intrathoracic organs (p < 0.0001). Elevated SUA was further independently related to an increased risk of all-cause mortality (p < 0.0001). Conclusions Our results are contrary to the proposed antioxidant, inhibitory effect of SUA against cancer and rather suggest high SUA to be a valuable long-term surrogate parameter, indicative for a life-style at increased risk for the development of cancer.     

Heterogeneity in risk of prostate cancer: A Swedish population‐based cohort study of competing risks and Type 2 diabetes mellitus

Most previous studies of prostate cancer have not taken into account that men in the studied populations are also at risk of competing event, and that these men may have different susceptibility to prostate cancer risk. The aim of our study was to investigate heterogeneity in risk of prostate cancer, using a recently developed latent class regression method for competing risks. We further aimed to elucidate the association between Type 2 diabetes mellitus (T2DM) and prostate cancer risk, and to compare the results with conventional methods for survival analysis. We analysed the risk of prostate cancer in 126,482 men from the comparison cohort of the Prostate Cancer Data base Sweden (PCBaSe) 3.0. During a mean follow‐up of 6 years 6,036 men were diagnosed with prostate cancer and 22,393 men died. We detected heterogeneity in risk of prostate cancer with two distinct latent classes in the study population. The smaller class included 9% of the study population in which men had a higher risk of prostate cancer and the risk was stronger associated with class membership than any of the covariates included in the study. Moreover, we found no association between T2DM and risk of prostate cancer after removal of the effect of informative censoring due to competing risks. The recently developed latent class for competing risks method could be used to provide new insights in precision medicine with the target to classify individuals regarding different susceptibility to a particular disease, reaction to a risk factor or response to treatment.     

Comparative quantitative assessment of a carcinogenic effect taking intercurrent mortality into account

The paper discusses the advantages offered by the statistical evaluation of experimental carcinogenic effect with due regard to mortality from concomitant pathology. The method used complex tables of contingents and analysis was carried out separately in 3 groups of tumors--independent of mortality, fatal and incidental ones. The method was compared with standard procedures which do not take care of the said mortality rate (table of contingents 2 X 2 and precise procedure of Fisher). The data on development of 1,2-dimethylhydrazine-induced tumors of the skin, uterus and ovaries in 5 strains of mice were used in the study.     

Type 2 diabetes mellitus,insulin‐use and risk of bladder cancer in a large cohort study

Type 2 diabetes mellitus (T2DM) is associated with increased bladder cancer incidence in some, but not all, studies. Many studies had limited statistical power and few examined risk by insulin‐use, duration of diabetes or cancer stage. We examined the association between T2DM and bladder cancer incidence in the Cancer Prevention Study II Nutrition Cohort, a large prospective study with information on insulin‐use and duration of diabetes. Diabetes and insulin‐use were ascertained from a questionnaire at study enrollment in 1992 or 1993 and updated in 1997 and every 2 years thereafter. During follow‐up through 2007, 1,852 cases of incident bladder cancer were identified among 172,791 participants. Multivariable adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using extended Cox regression modeling. There were no associations of T2DM with the risk of bladder cancer overall (RR = 1.01, 95% CI: 0.87–1.17), noninvasive disease (RR = 0.93, 95% CI: 0.76–1.14) or invasive disease (RR = 1.13, 95% CI: 0.91–1.40). Compared to participants without T2DM, risk of invasive bladder cancer was higher among participants who had had T2DM for >15 years (RR = 1.63, 95% CI: 1.09–2.43) and among those using insulin (RR = 1.64, 95% CI: 1.18–2.27). These results do not support an association of T2DM with overall bladder cancer incidence, but do suggest positive associations of long‐term T2DM and insulin‐use or other factors correlated with severe diabetes, with invasive bladder cancer incidence.     

Type 2 diabetes and the risk of mortality among patients with prostate cancer

Purpose

The aim of this study was to determine whether type 2 diabetes is associated with the incidence of prostate cancer mortality and all-cause mortality.

Methods

This study was conducted by linking four databases from the United Kingdom: the National Cancer Data Repository, the Clinical Practice Research Datalink, the Hospital Episodes Statistics database, and the Office for National Statistics database. The cohort consisted of men newly diagnosed with non-metastatic prostate cancer between 1 April 1998 and 31 December 2009, followed until 1 October 2012. Cox proportional hazard models were used to estimate adjusted hazard ratios with 95 % confidence intervals (CIs) of prostate cancer mortality and all-cause mortality comparing patients with to without type 2 diabetes. All models were adjusted for a number of potential confounders, which included excessive alcohol use, smoking, comorbidities, and prostate cancer-related variables.

Results

The cohort consisted of 11,920 patients, which included 1,132 (9.5 %) with preexisting type 2 diabetes. During a mean follow-up of 4.7 (SD 3.0) years, there were 3,605 deaths (incidence rate: 6.4 %/year) including 1,792 from prostate cancer (incidence rate: 3.3 %/year). Type 2 diabetes was associated with a 23 % increased risk of prostate cancer mortality (HR 1.23, 95 % CI 1.04–1.46) and a 25 % increased risk in all-cause mortality (HR 1.25, 95 % CI 1.11–1.40).

Conclusions

The results of this large population-based study indicate that type 2 diabetes is associated with an increased risk of prostate cancer mortality and all-cause mortality, which may signal an association between hyperinsulinemia or other diabetes-associated metabolic derangements and cancer aggressivity.     

Associations of type 2 diabetes and diabetes treatment with breast cancer risk and mortality: a population-based cohort study among British women

Purpose

There is great interest in whether type 2 diabetes and its treatments alter breast cancer risk and prognosis, but previous studies are inconclusive. We conducted a cohort study within the UK General Practice Research Database to investigate associations of type 2 diabetes and patterns of diabetes treatment with breast cancer risk and all-cause mortality.

Methods

We identified 52,657 women with type 2 diabetes, diagnosed between 1987 and 2007, and 30,210 randomly selected women without diabetes. We performed a time-dependent analysis using Cox proportional hazards models.

Results

Diabetes was associated with a 29?% increased overall breast cancer risk (95?% CI: 1.16–1.44), but the association markedly attenuated when adjusted for age, period of cohort entry, region, and body mass index (BMI) (HR: 1.12; 95?% CI: 0.98–1.29). Women with breast cancer and pre-existing diabetes had a 49?% (95?% CI: 1.17–1.88) increased all-cause mortality risk compared with women with breast cancer but without diabetes, after controlling for age, period, region, BMI, smoking, alcohol, and deprivation. Compared with sulfonylurea, we found weak evidence that metformin monotherapy (HR: 1.04; 95?% CI: 0.79–1.37) and insulin (HR: 1.33; 95?% CI: 0.63–2.83) modified breast cancer risk among women with diabetes.

Conclusions

We found weak evidence that diabetes is associated with a small increased risk of breast cancer. Among treated women, there is no evidence that anti-diabetes treatments modify the risk of developing breast cancer, with wide confidence intervals indicating imprecise effect estimates. Women with breast cancer and diabetes, however, had an increased all-cause mortality risk highlighting the potential importance of maintaining adequate glycemic control alongside anti-cancer treatments and subsequent follow-up.     

Body mass index, height, and the risk of ovarian cancer mortality in a prospective cohort of postmenopausal women.

Endogenous hormones may play a role in ovarian carcinogenesis. Postmenopausal obesity, although associated with higher circulating levels of estrogen and androgens, has not been linked consistently to ovarian cancer. The present study examined the relationship between body mass index (BMI), height, and ovarian cancer mortality among postmenopausal women in a large prospective mortality study of 300,537 women who were cancer free at enrollment in 1982 and had no history of hysterectomy or ovarian surgery. During 16 years of follow-up, 1,511 deaths occurred from ovarian cancer. Cox proportional hazard modeling was used to compute rate ratios (RRs) and to adjust for confounders. Ovarian cancer mortality rates were higher among overweight [BMI >/=25;RR, 1.16; 95% confidence interval (CI), 1.04-1.30] and obese women (BMI >/=30; RR, 1.26; 95% CI, 1.07-1.48) compared with women with BMI <25. Use of postmenopausal estrogens modified the association between BMI and ovarian cancer mortality (P = 0.05). The increased risk associated with obesity (BMI >/=30) was limited to women who never used postmenopausal estrogens (RR, 1.36; 95% CI, 1.12-1.66) and was not seen among ever users (RR, 0.93; 95% CI, 0.62-1.41). Height was positively associated with ovarian cancer mortality. Compared with women 152-156 cm tall, ovarian cancer mortality rates were lowest for the shortest women (RR, 0.72; 95% CI, 0.47-1.10 for women <152 cm) and highest for the tallest (RR, 1.41; 95% CI, 0.95-2.09 for women >/=177 cm). In this study, obesity and height appear to be independently associated with ovarian cancer mortality. The 36% increase in risk associated with obesity among women who had never used postmenopausal estrogens may have important public health implications because obesity is a growing problem in the United States.     

Central adiposity,obesity during early adulthood,and pancreatic cancer mortality in a pooled analysis of cohort studies

BackgroundBody mass index (BMI), a measure of obesity typically assessed in middle age or later, is known to be positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk.DesignWe conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity (e.g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood (ages 18–21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later (n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models.ResultsHigher waist-to-hip ratio (HR = 1.09, 95% CI 1.02–1.17 per 0.1 increment) and waist circumference (HR = 1.07, 95% CI 1.00–1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality (HR = 1.18, 95% CI 1.11–1.25 per 5 kg/m²), with increased risk observed in both overweight and obese individuals (compared with BMI of 21.0 to <23 kg/m², HR = 1.36, 95% CI 1.20–1.55 for BMI 25.0 < 27.5 kg/m², HR = 1.48, 95% CI 1.20–1.84 for BMI 27.5 to <30 kg/m², HR = 1.43, 95% CI 1.11–1.85 for BMI ≥30 kg/m²). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR = 1.05, 95% CI 1.01–1.10 per 5 kg/m²).ConclusionsOur results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life.     

Androgen receptor expression and breast cancer mortality in a population-based prospective cohort

Purpose

The increase in clinical trials with androgen receptor (AR)-targeting drugs emphasizes the need of clarifying the role of AR expression in different breast cancer subtypes. AR confers good prognosis in estrogen receptor positive (ER+) breast cancer, but its role in ER-negative (ER?) breast cancer is unclear. The aim of this study was to elaborate on previous findings of a differential prognostic role for AR depending on ER status, using breast cancer mortality (BCM) as endpoint, in a population-based cohort from the Malmö Diet and Cancer Study.

Methods

Immunohistochemical AR expression was assessed in 910 women with invasive breast cancer diagnosed 1991–2010, supplemented with clinicopathological information, vital status, and cause of death, with the last follow-up in December 2014 (median 10 years). Survival analyses according to AR status and AR/ER combinations were performed.

Results

AR expression was available for 671 tumors. AR+ (n = 573, 85%) was associated with favorable established tumor markers and lower BCM in univariable analysis, especially during the first 5 years following diagnosis [HR 0.4; 95% confidence intervals (CI) 0.2–0.7]. Multivariable analysis for short-term follow-up indicated higher BCM among patients with AR+ER? tumors (HR 3.5; 95% CI 1.4–9.1) than other AR and ER combinations.

Conclusions

AR expression added prognostic information to ER expression with respect to short-term prognosis. The worst prognosis was seen for patients with AR+/ER? tumors in short-term follow-up, supporting the pre-specified hypothesis. However, larger cohorts are needed for further characterization of the role of AR expression in ER? breast cancer.

     

Meat intake and bladder cancer risk in a Swedish prospective cohort

Background  High meat consumption could potentially increase the risk of bladder cancer, but findings from epidemiologic studies are inconsistent. We prospectively examined the association between meat intake and bladder cancer risk in a population-based cohort study. Methods  We prospectively followed 82,002 Swedish women and men who were free from cancer and completed a food-frequency questionnaire in 1997. Incident cases of bladder cancer were identified in the Swedish cancer registries. Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, smoking status, pack-years of smoking, and total energy intake. Results  During a mean follow-up of 9.4 years, 485 incident cases of bladder cancer (76 women and 409 men) were ascertained in the cohort. We observed no association between the intake of total or any specific type of meat and the risk of bladder cancer. The multivariate HRs (95% CIs) comparing the highest and the lowest category of intake were 1.05 (0.71–1.55) for total meat, 1.00 (0.71–1.41) for red meat, 1.01 (0.80–1.28) for processed meats, 0.96 (0.70–1.30) for chicken/poultry, and 0.92 (0.65–1.30) for fried meats/fish. The associations did not vary by sex or smoking status. Conclusions  These results do not support the hypothesis that intake of red meat, processed meat, poultry, or fried meats/fish is associated with the risk of developing bladder cancer.     

Alcohol intake,drinking patterns,and prostate cancer risk and mortality: a 30-year prospective cohort study of Finnish twins

Purpose

Alcohol intake may be associated with cancer risk, but epidemiologic evidence for prostate cancer is inconsistent. We aimed to prospectively investigate the association between midlife alcohol intake and drinking patterns with future prostate cancer risk and mortality in a population-based cohort of Finnish twins.

Methods

Data were drawn from the Older Finnish Twin Cohort and included 11,372 twins followed from 1981 to 2012. Alcohol consumption was assessed by questionnaires administered at two time points over follow-up. Over the study period, 601 incident cases of prostate cancer and 110 deaths from prostate cancer occurred. Cox regression was used to evaluate associations between weekly alcohol intake and binge drinking patterns with prostate cancer risk and prostate cancer-specific mortality. Within-pair co-twin analyses were performed to control for potential confounding by shared genetic and early environmental factors.

Results

Compared to light drinkers (≤3 drinks/week; non-abstainers), heavy drinkers (>14 drinks/week) were at a 1.46-fold higher risk (HR 1.46; 95 % CI 1.12, 1.91) of prostate cancer, adjusting for important confounders. Among current drinkers, binge drinkers were at a significantly increased risk of prostate cancer (HR 1.28; 95 % CI 1.06, 1.55) compared to non-binge drinkers. Abstainers were at a 1.90-fold higher risk (HR 1.90; 95 % CI 1.04, 3.47) of prostate cancer-specific mortality compared to light drinkers, but no other significant associations for mortality were found. Co-twin analyses suggested that alcohol consumption may be associated with prostate cancer risk independent of early environmental and genetic factors.

Conclusion

Heavy regular alcohol consumption and binge drinking patterns may be associated with increased prostate cancer risk, while abstinence may be associated with increased risk of prostate cancer-specific mortality compared to light alcohol consumption.

     

Sleep characteristics,light at night and breast cancer risk in a prospective cohort

Increasing numbers of women in the US are getting too little sleep. Inadequate sleep has been associated with impaired metabolic function and endocrine disruption. Sister Study cohort participants (n = 50,884), completed baseline and follow‐up questionnaires on sleep patterns. Incident breast cancers estrogen receptor (ER) status of the tumor were ascertained from questionnaires and medical records. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). Analyses of sleep characteristics reported at the first follow‐up interview included only participants who were breast cancer‐free at time of follow‐up interview. Over ～7 years of follow‐up, 2,736 breast cancer cases (invasive and ductal carcinoma in situ) were diagnosed. There was little evidence that usual sleep duration or other sleep characteristics were associated with breast cancer. However, relative to those with no difficulty sleeping, women who reported having difficulty sleeping ≥ 4 nights a week were at an increased risk of overall (HR = 1.32, 95% CI: 1.09–1.61) and postmenopausal breast cancer (HR = 1.51, 95% CI 1.24–1.85). Risk of ER+ invasive cancer was elevated for women who reported having a light or television on in the room while sleeping (HR = 1.20, 95% CI: 0.97–1.47) or who typically got less sleep than they needed to feel their best (HR = 1.21, 95% CI: 0.98–1.50). In our study, most sleep characteristics, including sleep duration, were not associated with an increased risk although higher risk was observed for some markers of inadequate or poor quality sleep.     

Sleep disruption,chronotype, shift work,and prostate cancer risk and mortality: a 30-year prospective cohort study of Finnish twins

Purpose

Sleep disruption and shift work have been associated with cancer risk, but epidemiologic evidence for prostate cancer remains limited. We aimed to prospectively investigate the association between midlife sleep- and circadian-related parameters and later prostate cancer risk and mortality in a population-based cohort of Finnish twins.

Methods

Data were drawn from the Older Finnish Twin Cohort and included 11,370 twins followed from 1981 to 2012. Over the study period, 602 incident cases of prostate cancer and 110 deaths from prostate cancer occurred. Cox regression was used to evaluate associations between midlife sleep duration, sleep quality, chronotype, and shift work with prostate cancer risk and prostate cancer-specific mortality. Within-pair co-twin analyses were employed to account for potential familial confounding.

Results

Compared to “definite morning” types, “somewhat evening” types had a significantly increased risk of prostate cancer (HR 1.3; 95 % CI 1.1, 1.6). Chronotype significantly modified the relationship between shift work and prostate cancer risk (p-interaction <0.001). We found no significant association between sleep duration, sleep quality, or shift work and prostate cancer risk in the overall analyses and no significant association between any sleep- or circadian-related parameter and risk in co-twin analyses. Neither sleep- nor circadian-related parameters were significantly associated with prostate cancer-specific mortality.

Conclusion

The association between sleep disruption, chronotype, and shift work with prostate cancer risk and mortality has never before been studied in a prospective study of male twins. Our findings suggest that chronotype may be associated with prostate cancer risk and modify the association between shift work and prostate cancer risk. Future studies of circadian disruption and prostate cancer should account for this individual-level characteristic.

     

Type 2 diabetes and colorectal cancer survival: The multiethnic cohort

This analysis examined type 2 diabetes (T2D) as a predictor of colorectal cancer (CRC) survival within the Multiethnic Cohort Study. Registry linkages in Hawaii and California identified 5,284 incident CRC cases. After exclusion of cases with pre‐existing cancer diagnosis within 1 year and systemic disease, the analytic dataset had 3,913 cases with 1,800 all‐cause and 678 CRC‐specific deaths after a mean follow‐up of 9.3 ± 5.2 years. Among CRC cases, 707 were diagnosed with T2D 8.9 ± 5.3 years before CRC. Cox regression with age as time metric was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for T2D status as predictor of CRC‐specific and all‐cause survival while adjusting for known confounders. Overall, CRC‐specific survival was not associated with pre‐existing T2D (HR = 0.84; 95% CI = 0.67–1.07). However, a significant interaction was seen for comorbidity (p_interaction = 0.03) with better survival among those without pre‐existing conditions (HR = 0.49; 95% CI = 0.25–0.96) while no association was seen in patients with comorbid conditions. All‐cause mortality was also not related to pre‐existing T2D (HR = 1.11; 95% CI = 0.98–1.27), but significantly elevated for individuals with T2D reporting comorbid conditions (HR = 1.36; 95% CI = 1.19–1.56). Stratification by T2D duration suggested higher CRC‐specific and all‐cause mortality among participants with a T2D history of ≥10 than <10 years. The findings were consistent across sex and ethnic subgroups. In contrast to previous reports, pre‐existing T2D had no influence on disease‐specific and all‐cause survival among CRC patients. Only participants with additional comorbidity and possibly those with long T2D duration experienced higher mortality related to T2D.     

Body mass index,height, and postmenopausal breast cancer mortality in a prospective cohort of US women

Objective: Epidemiologic evidence suggests a positive association between body mass, adult height, and postmenopausal breast cancer. However, most studies have not been large enough to examine the association across a very wide range of body mass or height, and few studies have assessed the relationship between body mass or height and postmenopausal breast cancer mortality. Methods: The relation between body mass index (BMI) and height and postmenopausal breast cancer mortality was examined in the American Cancer Society's Cancer Prevention Study II (CPS-II), a large prospective mortality study of US adults enrolled in 1982. After 14 years of follow-up, 2852 breast cancer deaths were observed among 424,168 postmenopausal women who were cancer-free at interview. Cox proportional hazards modeling was used to estimate relative risks and to control for potential confounding. Results: Breast cancer mortality rates increased continually and substantially with increasing BMI (rate ratio (RR) = 3.08, 95% confidence interval (CI) = 2.09–4.51 for BMI 40.0 compared to BMI 18.5–20.49). If causal, the multivariate-adjusted RR estimates in this study correspond to approximately 30–50% of breast cancer deaths among postmenopausal women in the US population being attributable to overweight. Breast cancer mortality also increased with increasing height up to 66 inches with RR = 1.64, (95% CI = 1.23–2.18) in women 66 inches tall compared to those < 60 inches. Conclusions: Postmenopausal obesity is an important and potentially avoidable predictor of fatal breast cancer in this study. These results underscore the importance of maintaining moderate weight throughout adult life.     

Yogurt consumption and risk of colorectal cancer in the Italian European prospective investigation into cancer and nutrition cohort

Fermented dairy products like yogurt have been suggested to protect against colorectal cancer (CRC). We conducted a prospective study on 45,241 (14,178 men; 31,063 women) volunteers of the EPIC-Italy cohort who completed a dietary questionnaire including specific questions on yogurt intake. During 12 years of follow-up, 289 volunteers were diagnosed with CRC. Hazard ratios (HRs) for the disease and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models, stratified by dietary questionnaire and adjusted for energy intake and other potential confounders. Yogurt intake was inversely associated with CRC risk. For the energy-adjusted model, HR for CRC in the highest versus lowest tertile of yogurt intake was 0.62 (95% CI, 0.46-0.83). In the full model adjusted for energy, simple sugar, calcium, fiber, animal fat, alcohol and red meat intake, as well as body mass index, smoking, education and physical activity, HR was 0.65 (95% CI, 0.48-0.89) in the highest versus lowest tertile. The protective effect of yogurt was evident in the entire cohort, but was stronger in men, although there was no interaction of sex with the yogurt-CRC association (p(interaction) 0.20, fully adjusted model). In our prospective study, high yogurt intake was significantly associated with decreased CRC risk, suggesting that yogurt should be part of a diet to prevent the disease. Investigation of larger cohorts is necessary to reveal any residual confounding of the association of yogurt intake with CRC risk.     

Energy balance and breast cancer risk: a prospective cohort study

Summary While there is evidence that breast cancer risk is positively associated with body mass index (in postmenopausal women) and energy intake and inversely associated with physical activity, few studies have examined breast cancer risk in association with energy balance, the balance between energy intake and expenditure. Therefore, in the cohort study reported here, we studied the independent and combined associations of vigorous physical activity, energy consumption, and body mass index (BMI), with breast cancer risk. The investigation was conducted in 49,613 Canadian women who were participants in the National Breast Screening Study (NBSS) and who completed self-administered lifestyle and food frequency questionnaires between 1980 and 1985. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000. During a mean 16.4 years of follow-up, we observed 2545 incident breast cancer cases. Due to exclusions for various reasons, the analyses were based on 40,318 subjects amongst whom there were 1673 incident cases of breast cancer. Participation in vigorous physical activity and body mass index were not independently associated with breast cancer risk in the total cohort. A statistically significant positive trend was observed, however, between energy intake and breast cancer risk (P _trend = 0.01). Although there was some variation in risk associated with vigorous physical activity, and BMI when the analyses were stratified by menopausal status, these interactions were not statistically significant. The interaction between menopausal status and energy intake, however, was of borderline statistical significance (P _interaction = 0.06), with a statistically significant increased risk of breast cancer associated with highest versus lowest quartile of energy intake among premenopausal women (Hazard Ratio [HR] = 1.45, 95% confidence interval [CI] = 1.13– 1.85, P _trend = 0.001). There was evidence of an increased risk of breast cancer associated with a relatively high body mass index among postmenopausal women in the highest quartile level of energy intake (Hazard Ratio [HR] = 1.72, 95% confidence interval [CI] = 1.01– 2.93, P _trend = 0.05). In addition, there was evidence of an increased risk of breast cancer among premenopausal, physically inactive, overweight/obese women who consumed ≥1972 kcal/day compared to physically active normal weight women who consumed <1972 kcal/day (HR = 1.60, 95% CI = 1.08–2.37). Our data suggest that obese premenopausal women with relatively high energy intake may be at increased risk of breast cancer. In addition, energy imbalance, represented by a relatively high energy intake, lack of participation in vigorous physical activity, and a relatively high body mass index, may be associated with increased breast cancer risk, particularly among premenopausal women.     

Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow‐up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center‐stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable‐adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95–1.11 and 1.02; 95% CI: 0.89–1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91–1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort.     

Plasma testosterone in the general population,cancer prognosis and cancer risk: a prospective cohort study

BackgroundTestosterone is an important anabolic hormone in humans and in vitro testosterone stimulates growth of lung and colon cancer cells. We tested the hypothesis that plasma testosterone associate with increased risk of cancer and with increased risk of early death after cancer.Materials and methodsPlasma testosterone was measured in 8771 20- to 94-year-old men and women who participated in a prospective study of the general population. Participants were included in 1981–1983 and followed for a median of 22 years (range: 0–30 years).ResultsDuring follow-up, 1140 men and 809 women developed cancer. For risk of early death after cancer, for men, after adjustment for age at diagnosis, tumour stage at diagnosis, and time since blood-sampling, the hazard ratio was 1.30 [95% confidence interval (CI) 1.03–1.65] for the 2nd quintile, 1.31 (1.02–1.67) for the 3rd quintile, 1.52 (1.19–1.93) for the 4th quintile, and 1.52 (1.20–1.91) for the 5th quintile, versus the 1st quintile. For women, corresponding hazard ratios were 1.09 (0.81–1.46), 1.17 (0.86–1.59), 1.03 (0.76–1.39), and 1.80 (1.32–2.46). For risk of cancer, multifactorially adjusted hazard ratios for risk of any cancer were 1.07 (95% CI 0.98–1.18) and 1.06 (0.93–1.22) for men and women, respectively, when testosterone doubled. For both men and women, a doubling of testosterone was not associated with risk of any cancer type.ConclusionsIn this prospective study of 8771 men and women from the general population followed for >30 years, increased levels of testosterone were associated with a 30%–80% increased risk of early death after cancer, but unchanged risk of incident cancer.     

Diabetes and risk of incident colorectal cancer in a prospective cohort of women

Objective  

To determine whether accounting for the time dynamics of diabetes exposure will change the risk estimates for colorectal cancer.