Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality

BACKGROUND.

Adiposity has been linked inconsistently with prostate cancer, and few studies have evaluated whether such associations vary by disease aggressiveness.

METHODS.

The authors prospectively examined body mass index (BMI) and adult weight change in relation to prostate cancer incidence and mortality in 287,760 men ages 50 years to 71 years at enrollment (1995–1996) in the National Institutes of Health‐AARP Diet and Health Study. At baseline, participants completed questionnaires regarding height, weight, and cancer screening practices, including digital rectal examinations and prostate‐specific antigen tests. Cox regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (95% CIs).

RESULTS.

In total, 9986 incident prostate cancers were identified during 5 years of follow‐up, and 173 prostate cancer deaths were ascertained during 6 years of follow‐up. In multivariate models, higher baseline BMI was associated with significantly reduced total prostate cancer incidence, largely because of the relationship with localized tumors (for men in the highest BMI category [≥40 kg/m²] vs men in the lowest BMI category [<25 kg/m²]: RR, 0.67; 95% CI, 0.50–0.89; P = .0006). Conversely, a significant elevation in prostate cancer mortality was observed at higher BMI levels (BMI <25 kg/m²: RR, 1.0 [referent group]; BMI 25–29.9 kg/m²: RR, 1.25; 95% CI, 0.87–1.80; BMI 30–34.9 kg/m²: RR, 1.46; 95% CI, 0.92–2.33; and BMI ≥35 kg/m²: RR, 2.12; 95% CI, 1.08–4.15; P = .02). Adult weight gain from age 18 years to baseline also was associated positively with fatal prostate cancer (P = .009), but not with incident disease.

CONCLUSIONS.

Although adiposity was not related positively to prostate cancer incidence, higher BMI and adult weight gain increased the risk of dying from prostate cancer. Cancer 2007. Published 2007 by the American Cancer Society.     

Metabolic syndrome and risk of bladder cancer: prospective cohort study in the metabolic syndrome and cancer project (Me‐Can)

There are little data on the putative association between factors in the metabolic syndrome (MetS) and risk of bladder cancer. In the Metabolic Syndrome and Cancer project (Me‐Can), measurements of height, weight, blood pressure and circulating levels of glucose, cholesterol, and triglycerides had been collected from 578,700 subjects in cohorts in Norway, Austria, and Sweden. We used Cox proportional hazard models to calculate relative risks (RRs) of bladder cancer by exposures divided into quintiles, in categories according to the World Health Organisation (WHO) and as a continuous standardized variable (z‐score with mean = 0 and standard deviation = 1) for each separate component and its standardized sum, a composite MetS score. RRs were corrected for random error in measurements. During a mean follow‐up of 11.7 years (SD = 7.6), 1,587 men and 327 women were diagnosed with bladder cancer. Significant associations with risk were found among men per one unit increment of z‐score for blood pressure, RR = 1.13 (95% CI 1.03–1.25), and the composite MetS score, RR = 1.10 (95% CI 1.01–1.18). Among women, glucose was nonsignificantly associated with risk, RR = 1.41 (95% CI 0.97–2.06). No statistically significant interactions were found between the components in the MetS in relation to bladder cancer risk. Hypertension and a composite MetS score were significantly but modestly associated with an increased risk of bladder cancer among men and elevated glucose was associated with a nonsignificant increase in risk among women.     

Body mass index in early and middle-late adulthood and risk of localised, advanced and fatal prostate cancer: a population-based prospective study

Background:

The relationships between body mass index (BMI) during early and middle-late adulthood and incidence of prostate cancer (PCa) by subtype of the disease (localised, advanced) and fatal PCa is unclear.

Methods:

A population-based cohort of 36 959 Swedish men aged 45–79 years was followed up from January 1998 through December 2008 for incidence of PCa (1530 localised and 554 advanced cases were diagnosed) and through December 2007 for PCa mortality (225 fatal cases).

Results:

From a competing-risks analysis, incidence of localised PCa was observed to be inversely associated with BMI at baseline (middle-late adulthood; rate ratio (RR) for 35 kg m^–2 when compared with 22 kg m^–2 was 0.69 (95% CI 0.52–0.92)), but not at age 30. For fatal PCa, BMI at baseline was associated with a nonstatistically significant increased risk (RR for every five-unit increase: 1.12 (0.88–1.43)) and BMI at age 30 with a decreased risk (RR for every five-unit increase: 0.72 (0.51–1.01)).

Conclusion:

Our results indicate an inverse association between obesity during middle-late, but not early adulthood, and localised PCa. They also suggest a dual association between BMI and fatal PCa – a decreased risk among men who were obese during early adulthood and an increased risk among those who were obese during middle-late adulthood.     

Midlife metabolic factors and prostate cancer risk in later life

Metabolic syndrome is associated with several cancers, but evidence for aggressive prostate cancer is sparse. We prospectively investigated the influence of metabolic syndrome and its components on risk of total prostate cancer and measures of aggressive disease in a cohort of Icelandic men. Men in the Reykjavik Study (n = 9,097, enrolled 1967–1987) were followed for incident (n = 1,084 total; n = 378 advanced; n = 148 high‐grade) and fatal (n = 340) prostate cancer until 2014. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for (1) measured metabolic factors at cohort entry (body mass index (BMI), blood pressure, triglycerides, fasting blood glucose) and (2) a metabolic syndrome score (range 0–4) combining the risk factors: BMI ≥30 kg/m²; systolic blood pressure (SBP) ≥130 or diastolic blood pressure (DBP) ≥85 mm Hg or taking antihypertensives; triglycerides ≥150 mg/dl; fasting blood glucose ≥100 mg/dl or self‐reported type 2 diabetes. Hypertension and type 2 diabetes were associated with a higher risk of total, advanced, high‐grade, and fatal prostate cancer, independent of BMI. Neither BMI nor triglycerides were associated with prostate cancer risk. Higher metabolic syndrome score (3–4 vs 0) was associated with a higher risk of fatal prostate cancer (HR 1.55; 95% CI: 0.89, 2.69; p trend = 0.08), although this finding was not statistically significant. Our findings suggest a positive association between midlife hypertension and diabetes and risk of total and aggressive prostate cancer. Further, metabolic syndrome as a combination of factors was associated with an increased risk of fatal prostate cancer.     

Acne and risk of prostate cancer

In a recent study, prostatectomy specimens from which Propionibacterium acnes was cultured were more likely to have inflammation than culture-negative specimens or specimens positive for other bacteria, leading the authors to hypothesize that P. acnes-mediated inflammation may contribute to prostate carcinogenesis. To indirectly explore associations between P. acnes and prostate cancer, we investigated severe acne, as measured by tetracycline use for 4 or more years, in relation to incident prostate cancer in the Health Professionals Follow-up Study. On the 1992 follow-up questionnaire, participants were asked whether they had ever used "tetracycline for at least 2 months at a time (e.g., for acne or other reason)" and their duration of use. Prostate cancer diagnoses were ascertained on each subsequent biennial questionnaire and confirmed by medical record review. Between 1992 and 2002, 2,147 cases of prostate cancer were reported among 34,629 eligible participants. Men who used tetracycline for 4 or more years had a significantly higher risk of prostate cancer (16 cases, 1,569 person-years) than men who did not use tetracycline (2,071 cases, 304,822 person-years, multivariable-adjusted RR = 1.70, 95% CI: 1.03-2.80). Although intriguing, this finding should be viewed cautiously because of the small number of exposed cases, indirect assessment of severe acne, and complex etiology of acne, which is not limited to P. acnes infection. Therefore, additional biologic and epidemiologic studies are necessary to determine and elucidate the possible role of P. acnes infection in prostate carcinogenesis.     

Weight change and prostate cancer incidence and mortality

The relationship between obesity and prostate cancer risk has been studied extensively but with inconsistent findings, particularly for tumor aggressiveness. Few studies have investigated weight change and prostate cancer incidence or mortality. Using the Melbourne Collaborative Cohort Study, which recruited 17,045 men aged between 40 and 69 years at study entry, we investigated associations between reported weight and body mass index (BMI) at age 18 and measured at study entry, height, weight change between age 18 and study entry and prostate cancer incidence and mortality. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. During follow-up (mean = 15 years) of 16,514 men, we ascertained 1,374 incident prostate cancers of which 410 were classified as aggressive, and 139 deaths from prostate cancer. The incidence of all prostate cancer was not associated with body size or weight change. Weight and BMI at study entry were positively associated with aggressive prostate cancer risk (HR = 1.06, 95% CI: 1.00-1.13 per 5 kg; HR = 1.27, 95% CI: 1.08-1.49 per 5 kg/m(2)) and prostate cancer mortality (HR = 1.12, 95% CI: 1.01-1.23 per 5 kg; HR = 1.49, 95% CI: 1.11-2.00 per 5 kg/m(2)). Weight gain was positively associated with prostate cancer mortality (HR = 1.13, 95% CI: 1.02-1.26 per 5 kg increment); the HR for ≥ kg weight gain between age 18 and study entry compared to <5 kg gain over this period was 1.84, 95% CI: 1.09-3.09. Higher adult weight and BMI increases the risk of aggressive prostate cancer and mortality from prostate cancer. Weight gain during adult life is associated with increased prostate cancer mortality.     

Association of body mass index and height with risk of prostate cancer among middle-aged Japanese men

In a population-based prospective study of 49 850 Japanese men, body mass index and height were not significantly associated with risk of prostate cancer (311 cases), although small positive effects could not be ruled out in advanced cases (91 cases).     

Metabolic risk factors and primary liver cancer in a prospective study of 578,700 adults

Initial studies have indicated diabetes and obesity to be risk factors for hepatocellular carcinoma; but the association between other metabolic risk factors and primary liver cancer (PLC) has not been investigated. The metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway, Austria and Sweden with data on 578,700 subjects. We used Cox proportional hazard models to calculate relative risks (RRs) of PLC by body mass index (BMI), blood pressure and plasma levels of glucose, cholesterol and triglycerides as continuous standardized variables (z-score with mean = 0 and standard deviation (SD) = 1) and their standardized sum of metabolic syndrome (MetS) z-score. RRs were corrected for random error in measurements. During an average follow-up of 12.0 years (SD = 7.8), 266 PLCs were diagnosed among cohort members. RR of liver cancer per unit increment of z-score adjusted for age, smoking status and BMI and stratified by birth year, sex and sub-cohorts, was for BMI 1.39 (95% confidence interval (CI) 1.24-1.58), mid blood pressure 2.08 (0.95-4.73), blood glucose 2.13 (1.55-2.94) cholesterol 0.62 (0.51-0.76) and serum triglycerides 0.85 (0.65-1.10). The RR per one unit increment of the MetS z-score was 1.35 (1.12-1.61). BMI, glucose and a composite MetS score were positively and cholesterol negatively associated with risk of liver cancer.     

Case-control study of anthropometric measures and prostate cancer risk

A population-based case-control study of 988 stage T2 or greater prostate cancer cases and 1063 controls was conducted in Alberta from November 1997 to December 2000 to examine the influence of anthropometric risk factors on the risk of prostate cancer using several different measures. An in-person interview was conducted, and all anthropometric measurements were taken using standardized methods. Respondents also recalled their body weight at each decade from age 20 to the referent year. Several anthropometric variables were derived, and unconditional logistic regression analyses were performed. The multivariable odds ratios, when comparing the highest to the lowest quartile were: for body mass index, OR = 1.12 (95% CI 0.85-1.47); for waist-hip ratio, OR = 1.07 (0.83-1.38); for height, OR = 0.78 (0.60-1.02); for weight, OR = 0.91 (0.70-1.18); for weight gain since age 20, OR = 0.91 (0.70-1.19); and for difference between minimum and maximum adult weight, OR = 0.89 (0.69-1.16). Our study provides evidence for no association between any measures of anthropometry including several derived measures of changes in weight over lifetime and prostate cancer risk.     

Smoking and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition

Background:

Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported.

Methods:

During 1992 and 2000, lifestyle information was assessed via questionnaires and personal interview in a cohort of 145 112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer.

Results:

Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR=0.90, 95% CI: 0.83–0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR=1.81, 95% CI: 1.11–2.93; RR=1.38, 95% CI: 1.01–1.87, respectively).

Conclusion:

The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies.     

Use of terbinafine and risk of death in patients with prostate cancer: A population-based cohort study

Terbinafine is used for the treatment of several superficial fungal infections. In silico analyses and animal models suggest that terbinafine might have an anti-tumor effect. We aimed to explore whether subsequent administration of terbinafine might be associated with a lower mortality rate in patients with prostate cancer. We identified patients diagnosed with prostate cancer between July 2005 and December 2014 from the Swedish Cancer Registry, and linked them to the Swedish Prescribed Drug Register to ascertain subsequent use of terbinafine. A total of 799 patients received oral treatment of terbinafine during the study period with a mortality rate of 18.6 per 1,000 person-years. Compared to patients who did not use terbinafine and adjusting for a range of confounding factors, patients that received oral treatment of terbinafine had a decreased risk of death from prostate cancer (HR, 0.53; 95% CI, 0.38–0.73) and a decreased risk of death overall (HR, 0.64; 95% CI, 0.52–0.77). To account for indication bias, we further identified 907 patients who received topical use of terbinafine. However, the risk of death from prostate cancer in patients with topical use of terbinafine was 0.92 (95% CI 0.74–1.12) and the risk of death overall was 1.03 (95% CI 0.91–1.17) as compared to the controls, which suggests that there was no association between risk of death in patients with prostate cancer with topical use of terbinafine. These findings suggest that this drug's potential anti-tumor effect needs to be explored further.     

Alcohol consumption and prostate cancer risk: results from the Melbourne collaborative cohort study

Although there is little evidence to support an association between alcohol consumption and prostate cancer risk, questions remain concerning the effect on aggressive and nonaggressive tumours and the pattern and type of alcohol consumed. In a prospective cohort of 16,872 men aged 27-70 years at recruitment and followed-up from 1994 to the end of 2003, 732 incident prostate cancers were identified through the local population cancer registry, including 132 aggressive cases and 53 prostate cancer deaths. Detailed information on alcohol consumption was taken at baseline by trained interviewers using a structured questionnaire. Overall, alcohol intake was not associated with prostate cancer incidence. Compared to abstainers, men consuming 1-19 g/d of alcohol had a slightly reduced incidence of aggressive prostate cancers (hazard ratio 0.67; 95% confidence interval (CI) 0.43, 1.06) and prostate cancer mortality (hazard ratio 0.56; 95% CI 0.28, 1.14), but their risk of nonaggressive prostate cancers was close to unity (hazard ratio 1.09; 95% CI 0.85, 1.40). No significant association with pattern of drinking or type of alcoholic beverage was found. Our results show that alcohol consumption does not influence overall prostate cancer incidence but we found suggestive evidence that alcohol consumption might decrease the incidence of aggressive prostate cancer and mortality.     

Prospective study of body mass index,physical activity and thyroid cancer

Increased body size and physical inactivity are positively related to risk of several cancers, but only few epidemiologic studies have investigated body‐mass index (BMI) and physical activity in relation to thyroid cancer. We examined the relations of BMI and physical activity to thyroid cancer in a prospective cohort of 484,326 United States men and women, followed from 1995/1996 to 2003. During 3,490,300 person‐years of follow‐up, we documented 352 newly incident cases of thyroid cancer. The multivariate relative risks (RR) of thyroid cancer for BMI values of 18.5–24.9 (reference), 25.0–29.9 and ≥30 kg m^?2 were 1.0, 1.27 and 1.39 [95% confidence interval (CI) = 1.05–1.85]. Adiposity predicted papillary thyroid cancers (RR comparing extreme BMI categories = 1.47; 95% CI = 1.03–2.10) and, based on small numbers, suggestively predicted follicular thyroid cancers (RR = 1.49; 95% CI = 0.79–2.82) and anaplastic thyroid cancers (RR = 5.80; 95% CI = 0.99–34.19). No relation with BMI was noted for medullary thyroid cancers (RR = 0.97; 95% CI = 0.27–3.43). The positive relation of BMI to total thyroid cancer was evident for men but not for women. However, the test of interaction (p = 0.463) indicated no statistically significant gender difference. Physical activity was unassociated with thyroid cancer. The RRs of total thyroid cancer for low (reference), intermediate, and high level of physical activity were 1.0, 1.01 and 1.01 (95% CI = 0.76–1.34, p for trend = 0.931), respectively. Our results support an adverse effect of adiposity on risk for developing total and papillary, and possibly follicular thyroid cancers. Based on only 15 cases, adiposity was unrelated to medullary thyroid cancers. Physical activity was unrelated to total thyroid cancer.     

Metabolic factors and the risk of colorectal cancer in 580,000 men and women in the metabolic syndrome and cancer project (Me‐Can)

BACKGROUND:

The metabolic syndrome (MetS) has been related to an increased risk of colorectal cancer, but the modest size of previous studies precluded detailed characterization of the role of individual MetS factors and their interaction on risk.

METHODS:

In the Metabolic Syndrome and Cancer Project (Me‐Can), data on body mass index (BMI), blood pressure, and blood levels of glucose, cholesterol, and triglycerides were available for 578,700 men and women. The mean age of participants at baseline was 44 years, and the mean follow‐up was 12 years. Relative risks (RR) of colorectal cancer per 1 standard deviation increment in Z score of factors and for a combined MetS score, were calculated from Cox regression models, including adjustment for potential confounders.

RESULTS:

During follow‐up, 2834 men and 1861 women were diagnosed with colorectal cancer. The RR of colorectal cancer for the MetS score was 1.25 (95% confidence interval [CI], 1.18‐1.32) in men, and 1.14 (95% CI, 1.06‐1.22) in women. Significant associations also were observed in men for BMI (RR, 1.07; 95% CI, 1.02‐1.13), blood pressure (RR, 1.10; 95% CI, 1.02‐1.18), and triglycerides (RR, 1.17; 95% CI, 1.06‐1.28) and, in women, for BMI (RR, 1.08; 95% CI, 1.01‐1.15). There was no significant positive interaction between the metabolic factors on risk.

CONCLUSIONS:

The combination of metabolic factors and some separate factors was related to an increased risk of colorectal cancer, but there was no interaction between metabolic factors. Cancer 2011;. © 2010 American Cancer Society.     

A prospective study on intake of animal products and risk of prostate cancer

Objective: Association between animal products and prostate cancer have been observed in numerous observational studies, but it is not clear whether the high fat content of these foods or some other component accounts for these associations. We examine these associations among 51,529 men who contributed detailed dietary data. Methods: Participants of the Health Professionals Follow-Up Study completed a semiquantitative food-frequency questionnaire in 1986, and subsequently in 1990 and 1994. Other data on potential risk factors were collected at baseline and in subsequent questionnaires during follow-up. Between 1986 and 1996, 1897 total cases of prostate cancer (excluding stage A₁) and 249 metastatic cancers were identified. We used pooled logistic regression for analyses of diet and prostate cancer. Results: Intakes of total meat, red meat, and dairy products were not associated with risk of total or advanced prostate cancer. An elevated risk for metastatic prostate cancer was observed with intake of red meat (relative risk (RR) = 1.6 for top vs. bottom quintile comparison, 95% confidence interval (CI) = 1.0–2.5); this association was slightly attenuated after controlling for saturated and -linolenic fatty acids (RR = 1.5, 95% CI = 0.88–2.5). Processed meats, bacon and beef, pork or lamb as a main dish each contributed to an elevated risk of metastatic prostate cancer. Dairy product intake increased risk of metastatic prostate cancer (RR = 1.4, 95% CI = 0.91–2.2 for top vs. bottom quintile comparison), but no association remained after controlling for calcium and other fatty acids. A high intake in both red meat and dairy product was associated with a statistically significant two-fold elevation in risk of metastatic prostate cancer, compared to low intake of both products; however, most of the excess risk could be explained by known nutritional components of these foods. Conclusions: Intakes of red meat and dairy products appear to be related to increased risk of metastatic prostate cancer. While known nutrients, such as calcium and fatty acids, may explain most of the dairy association observed, it appears that a portion of the risk of metastatic prostate cancer associated with red meat intake remains unexplained.     

Prospective study of physical activity in different periods of life and the risk of ovarian cancer

Only few studies have assessed the role of physical activity in the etiology of ovarian cancer, and the results have been inconclusive. We studied associations between physical activity and risk of ovarian cancer in 96,541 women aged 30-49 at enrollment in a prospective study in Norway and Sweden. Participants reported physical activity level at ages 14, 30 and at enrollment, and participation in competitive sports. Complete follow-up through 2001/2002 was achieved by linkage to national registries. The relation between physical activity and ovarian cancer incidence was assessed using multivariate Cox proportional hazard models. During an average 11.1 years of follow-up, there were 264 ovarian cancer cases (including 81 borderline tumors) diagnosed at a mean age of 49 years. Highly physically active women at cohort enrollment had a similar risk of ovarian cancer as women reporting no activity (multivariate relative risk RR = 1.08, 95% CI 0.53-2.18). Physical activity at age 30 or at age 14 did not either afford any protection from ovarian cancer, nor did a consistently high level of activity from younger ages until enrollment. Results were similar for invasive and borderline tumors, and for different subgroups of women classified according to other known risk factors for ovarian cancer. In our study of primarily premenopausal women, physical activity at different ages did neither reduce nor increase risk of ovarian cancer. In the context of the inconsistent scientific literature, our findings probably reflect that physical activity is not causally related with ovarian cancer.     

Prospective study of Type 2 diabetes mellitus,anti‐diabetic drugs and risk of prostate cancer

Type 2 diabetes mellitus (T2DM) has consistently been associated with decreased risk of prostate cancer; however, if this decrease is related to the use of anti‐diabetic drugs is unknown. We prospectively studied men in the comparison cohort in the Prostate Cancer data Base Sweden 3.0, with data on T2DM, use of metformin, sulfonylurea and insulin retrieved from national health care registers and demographic databases. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of prostate cancer, adjusted for confounders. The study consisted of 612,846 men, mean age 72 years (standard deviation; SD = 9 years), out of whom 25,882 men were diagnosed with prostate cancer during follow up, mean time of 5 years (SD = 3 years). Men with more than 1 year's duration of T2DM had a decreased risk of prostate cancer compared to men without T2DM (HR = 0.85, 95% CI = 0.82–0.88) but among men with T2DM, those on metformin had no decrease (HR = 0.96, 95% CI = 0.77–1.19), whereas men on insulin (89%) or sulfonylurea (11%) had a decreased risk (HR = 0.73, 95% CI = 0.55–0.98), compared to men with T2DM not on anti‐diabetic drugs. Men with less than 1 year's duration of T2DM had no decrease in prostate cancer risk (HR = 1.11, 95% CI = 0.95–1.31). Our results gave no support to the hypothesis that metformin protects against prostate cancer as recently proposed. However, our data gave some support to an inverse association between T2DM severity and prostate cancer risk.     

A prospective cohort study of red wine consumption and risk of prostate cancer

In light of recent, strong inverse findings between lifetime red wine consumption and prostate cancer among younger men, we revisited our previous cohort analysis to more thoroughly investigate red wine consumption and prostate cancer in the Health Professionals Follow-up Study (HPFS). In 1986, HPFS participants reported their average consumption of red wine, white wine, beer and liquor during the past year, and their change in alcohol consumption over the prior 10 years. Prostate cancer diagnoses were ascertained on each biennial questionnaire and confirmed by medical record review. Between 1986 and 2002, 3,348 cases of prostate cancer were diagnosed among 45,433 eligible participants. Using men who did not consume red wine as the reference, no linear trend was observed between red wine consumption and prostate cancer in the full analytic cohort (p-trend = 0.57). Among men with unchanged alcohol consumption in the prior 10 years, and those additionally <65 years of age, slightly lower risks were observed for men who consumed 4 glasses/week, resulting in a lack of linear trend. These findings suggest that red wine does not contribute appreciably to the etiology of prostate cancer.     

Reduced risk of prostate cancer among patients with diabetes mellitus

Although diabetes mellitus is associated with an increased risk of several malignancies, a negative association with prostate cancer is biologically most plausible. The epidemiologic evidence is, however, inconsistent, limited and based mostly on small studies. We present results from a large, population-based cohort study in Sweden, where we assessed prostate cancer risk among patients hospitalized for diabetes mellitus. The cohort was composed of patients identified in the Swedish In-Patient Register as having a hospital discharge diagnosis of diabetes mellitus in 1965-1994. The follow-up was done by linkages with the national cancer register and other population-based registers. Standardized incidence ratios (SIRs), with 95% confidence interval (CI), were used as a measure of relative risk. After complete exclusion of the first year of follow-up (to avoid selection bias), 135,950 men remained in the cohort, contributing 827,099 years of follow-up to the study. A total of 2,455 incident cases of primary prostate cancer were identified during 1-31 years of follow-up, yielding an overall SIR of 0.91 (95% CI 0.87-0.94); this risk reduction was more pronounced among patients who have been hospitalized for diabetic complications (SIR = 0.82; 95% CI 0.74-0.91). We found no consistent trends in risk related to age at first hospitalization or to duration of follow-up. We did find a small, but significantly decreased risk of prostate cancer among men who had been hospitalized for diabetes mellitus.     

Plasma phospholipid fatty acids,dietary fatty acids and prostate cancer risk

Animal and experimental studies have demonstrated that long‐chain n‐3 fatty acids inhibit the development of prostate cancer, whereas n‐6 fatty acids might promote it. We performed a case–cohort analysis within the Melbourne Collaborative Cohort Study using a random sample of 1,717 men and 464 prostate cancer cases to investigate associations between fatty acids assessed in plasma phospholipids (PPLs) or diet (estimated using a 121‐item food frequency questionnaire) and prostate cancer risk. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. Prostate cancer risk was positively associated with %PPL saturated fatty acids (SFAs); HR [95% CI] = 1.51 [1.06, 2.16] (Q5 vs. Q1, fifth vs. first quintile); p‐trend = 0.003. HRs (Q5 to Q2 vs. Q1) were significantly elevated for %PPL palmitic acid. %PPL oleic acid was inversely associated with risk, HR = 0.62 [0.43, 0.91] (Q5 vs. Q1); p‐trend = 0.04. No statistically significant linear trends were observed for dietary intakes. The HRs were elevated for moderate intakes of linoleic acid (Q2 and Q3 vs. Q1, 1.58 [1.10, 2.28] and 1.70 [1.18, 2.46], respectively), but the increase was not significant for higher intakes (Q4 and Q5). No association varied significantly by tumour aggressiveness (all p‐homogeneity > 0.1). Prostate cancer risk was positively associated with %PPL SFA, largely attributable to palmitic acid and inversely associated with %PPL monounsaturated fatty acids, largely attributable to oleic acid. Higher risks were also observed for dietary n‐6 polyunsaturated fats, primarily linoleic acid.