Circulating enterolactone and risk of endometrial cancer

It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer.     

Prospective study of blood metabolites associated with colorectal cancer risk

Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case–control study to search for risk‐associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In this study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk [odds ratios per standard deviation increase of transformed metabolites: 0.31–1.98; p values: 0.002–1.25 × 10^?10]. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer.     

Association of diabetes mellitus with prostate cancer: Nested case–control study (Prostate testing for cancer and Treatment study)

Observational studies suggest that diabetes is associated with a decreased risk of prostate cancer, but few are population based or have investigated associations with cancer stage or duration of diabetes. We report a case–control study nested within the population‐based Prostate testing for cancer and Treatment (ProtecT) study ISRCTN20141297. Men aged 50–69 years based around 9 UK cities were invited for a prostate‐specific antigen (PSA) test between June 2002 and November 2006. Amongst 55,215 PSA‐tested men, 1,966 had histologically confirmed prostate cancer; of these, 1,422 (72.3%) completed the questionnaire and 1,291 (65.7%) had complete data for analysis. We randomly selected 6,479 age‐ (within 5 years) and general practice‐matched controls. The prevalence of diabetes was 89/1,291 (6.9%) in cases and 555/6,479 (8.6%) in controls. Diabetes was associated with a reduced risk of prostate cancer (odds ratio = 0.78; 95% confidence interval: 0.61–0.99). There was weak evidence that the inverse association was greater for well‐ versus poorly differentiated cancers (p = 0.07). The magnitude of the inverse association did not change with increasing duration of diabetes (p for trend = 0.95). Diabetes is associated with a decreased risk of PSA‐detected prostate cancer. These data add to the evidence of the association of diabetes with prostate cancer in the PSA era.     

Relation of serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 to risk of prostate cancer (United States)

Objective: Insulin-like growth factor I (IGF-I) exerts potent mitogenic and antiapoptotic effects on prostatic epithelial cells. Insulin-like growth factor binding protein-3 (IGFBP-3) modulates the effects of IGF-I, and independently induces apoptosis and inhibits cell growth. Previous studies have inconsistently associated IGF-I and IGFBP-3 with prostate cancer. To try and further clarify these potential associations, we undertook a sibling-matched case–control study. Methods: Serum IGF-I and IGFBP-3 were determined for 845 men (408 cases and 437 sibling controls). Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the serum IGF levels and prostate cancer. Results: Among all study subjects, only the molar ratio of IGF-I to IGFBP-3 was associated with prostate cancer: comparing those in the highest to lowest quartiles gave an OR = 1.62 (95% CI = 1.02–2.57, trend-p = 0.04). Among men with clinically less aggressive disease, we observed positive associations between prostate cancer and high levels of IGF-I (OR = 2.78, 95% CI = 1.06–6.80, trend-p = 0.03), and IGFBP-3 (OR = 2.68, 95% CI = 1.08–6.80, trend-p = 0.04). Simultaneously modeling both left the IGF-I result essentially unchanged, while substantially weakening the IGFBP-3 association. Conclusions: We found that a high IGF-I to IGFBP-3 molar ratio was associated with an increased risk of prostate cancer. Furthermore, high IGF-I was associated with increased risk of prostate cancer among men with less advanced disease at diagnosis. These results lend support to the hypothesis that IGF-I, or the IGF-I to IGFBP-3 molar ratio, is an important risk factor for prostate cancer.     

Circulating leukocyte telomere length and risk of overall and aggressive prostate cancer

Background:

Recent large-scale prospective studies suggest that long telomeres are associated with an increase cancer risk, counter to conventional wisdom.

Methods:

To further clarify the association between leukocyte telomere length (LTL) and prostate cancer, and assess genetic variability in relation to both LTL and prostate cancer, we performed a nested case–control study (922 cases and 935 controls). The participants provided blood in 1993–1995 and were followed through August 2004 (prostate cancer incidence) or until 28 February 2013 (lethal or fatal prostate cancer). Relative LTL was measured by quantitative PCR and was calculated as the ratio of telomere repeat copy number to a single gene (36B4) copy number (T/S). Genotyping was performed using the TaqMan OpenArray SNP Genotyping Platform. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of all prostate cancer and subtypes defined by Gleason grade, stage and lethality (metastasis or death).

Results:

We observed a positive association between each s.d. increase in LTL and all (multivariable-adjusted OR 1.11, 95% CI: 1.01–1.22), low-grade (OR 1.13, 95% CI:1.01–1.27), and localised (OR 1.12, 95% CI:1.01–1.24) prostate cancer. Associations for other subtypes were similar, but did not reach statistical significance. In subgroup analyses, associations for high grade and advanced stage (OR=2.04, 95% CI 1.00–4.17; P_interaction=0.06) or lethal disease (OR=2.37, 95% CI 1.19–4.72; P_interaction=0.01) were stronger in men with a family history of the disease compared with those without. The minor allele of SNP, rs7726159, which has previously been shown to be positively associated with LTL, showed an inverse association with all prostate cancer risk after correction for multiple testing (P=0.0005).

Conclusion:

In this prospective study, longer LTL was modestly associated with higher risk of prostate cancer. A stronger association for more aggressive cancer in men with a family history of the disease needs to be confirmed in larger studies.     

A prospective evaluation of plasma polyphenol levels and colon cancer risk

Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre‐diagnostic plasma polyphenols and colon cancer risk in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (q_values) was computed to control for multiple comparisons. All statistical tests were two‐sided. After false discovery rate correction and in continuous log₂‐transformed multivariable models, equol (odds ratio [OR] per log₂‐value, 0.86, 95% confidence interval [95% CI] = 0.79–0.93; q_value = 0.01) and homovanillic acid (OR per log₂‐value, 1.46, 95% CI = 1.16–1.84; q_value = 0.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (OR = 0.61, 95% CI = 0.41–0.91, p_trend = 0.003), while homovanillic acid concentrations were positively associated with colon cancer development (OR = 1.72, 95% CI = 1.17–2.53, p_trend < 0.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis.     

Alcohol consumption and PSA‐detected prostate cancer risk—A case‐control nested in the ProtecT study

Alcohol is an established carcinogen but not an established risk factor for prostate cancer, despite some recent prospective studies suggesting increased risk among heavy drinkers. The aim of this study was to investigate the role of alcohol on prostate‐specific antigen (PSA) levels and prostate cancer risk. Two thousand four hundred PSA detected prostate cancer cases and 12,700 controls matched on age and general practice were identified through a case‐control study nested in the PSA‐testing phase of a large UK‐based randomized controlled trial for prostate cancer treatment (ProtecT). Linear and multinomial logistic regression models were used to estimate ratios of geometric means (RGMs) of PSA and relative risk ratios (RRRs) of prostate cancer by stage and grade, with 95% confidence intervals (CIs), associated with weekly alcohol intake and drinking patterns. We found evidence of lower PSA (RGM 0.98, 95% CI: 0.98–0.99) and decreased risk of low Gleason‐grade (RRR 0.96; 95%CI 0.93–0.99) but increased risk of high‐grade prostate cancer (RRR 1.04; 95%CI 0.99–1.08; p_difference=0.004) per 10 units/week increase in alcohol consumption, not explained by current BMI, blood pressure, comorbidities, or reverse causation. This is the first large population‐based study to find evidence of lower PSA levels for increasing alcohol consumption, with potential public health implications for the detection of prostate cancer. Our results also support a modestly higher risk of high‐grade disease for heavy drinkers, but require independent replication to establish the nature of the association of alcohol with low‐grade disease, preferably in cohorts with a heterogeneous case‐mix.     

Association between plasma cholesterol and prostate cancer in the PSA era

We previously found that statin users had a lower risk of advanced and possibly high-grade prostate cancer compared with nonusers. We hypothesize that statins' effects on cholesterol synthesis may explain those findings because prostate cancer cells exhibit cholesterol dysregulation. Thus, we investigated whether low plasma cholesterol is associated with prostate cancer overall and by stage and grade. Participants were drawn from the 18,018 members of the Health Professionals Follow-Up Study who provided blood in 1993-1995. We ascertained 698 incident cases through January 2000. Controls were 698 men who had a PSA test and were matched to cases. Plasma cholesterol was measured enzymatically. Conditional logistic regression was used to estimate multivariable ORs and 95% CIs of total, clinically organ-confined (n = 518), advanced (T3b or worse; n = 61), low-grade (Gleason sum < 7; n = 386) and high-grade (Gleason sum > or = 7, n = 247) disease. Low cholesterol (<25th percentile vs. > or =25th percentile) was not associated with total (OR = 0.93, 95% CI: 0.72-1.20), organ-confined (OR = 0.87, 95% CI: 0.64-1.18) or low-grade (OR = 1.06, 95% CI: 0.75-1.51) disease. However, men with low cholesterol had a lower risk of high-grade disease (OR = 0.61, 95% CI: 0.39-0.98), especially if organ-confined (OR = 0.54, 95% CI: 0.29-0.99). The association for advanced disease appeared inverse, but number of cases was small (OR = 0.42, 95% CI: 0.13-1.36). Associations remained after excluding cholesterol-lowering drug users. These results coupled with prior statin findings suggest that mechanistic studies on cholesterol metabolism should be pursued to understand a possible target for preventing poorly differentiated prostate cancers.     

Obesity and the risk of prostate cancer (United States)

The role of obesity in prostate cancer etiology remains controversial. A recent report suggested that obese men younger than age 60 may have a lower risk of developing prostate cancer than men the same age who are not obese. The current study used a nested, matched case–control study design and data collected in the General Practice Research Database between January 1991 and December 2001 to assess the association between body mass index (BMI) and the risk of incident prostate cancer. Seven hundred and thirty cases of prostate cancer with adequate information on BMI were identified and matched to 2740 controls on age, sex, general practice, and index date. Obese men (BMI ≥ 30.0 kilograms [kg]/square of height in meters [m²]) were at lower risk of developing prostate cancer (AOR=0.78, 95% CI: 0.56, 1.09) compared to normal weight men (BMI=23.0–24.9 kg/m²), and the data best fit an inverse quadratic model for the relation between BMI and the risk of prostate cancer. This study provides modest support for a protective association between obesity and the risk of incident prostate cancer.     

Transient increase in breast cancer risk after giving birth: postpartum period with the highest risk (Sweden)

Objective: Identify time-points when the elevated postpartum maternal breast cancer risk peaks. Methods: A case–control study nested within the Swedish Fertility Register included 34,018 breast cancer cases from the Swedish Cancer Register between 1961 and 1995. From the Fertility Register, 170,001 eligible subjects matched to the cases by age were selected as controls. Analysis contrasted risk between uniparous (7084 cases and 31,703 controls) and nulliparous (5411 cases and 22,580 controls) women and between biparous (13,239 cases and 65,858 controls) and uniparous women. Logistic regression analysis included indicator variables representing each year of age, ages at delivery, and time since delivery. Results: Comparing uniparous with nulliparous women the transient increase in maternal breast cancer risk peaked 5 years following delivery (odds ratio = 1.49, 95% confidence interval 1.01–2.20) and leveled off 15 years postpartum. Biparous women had a transient increase in risk that was lower at its peak than that of uniparous women, occurring about 3 years following second delivery. Conclusions: A time window of 5 years postpartum when maternal breast cancer risk is highest was observed. Establishing timing of peak transient increase in postpartum breast cancer risk may define the latent period required for pregnancy hormones in promoting progression of breast cells that have undergone early stages of malignant transformation.     

Foods, nutrients and prostate cancer

OBJECTIVE: To examine the risk of prostate cancer associated with foods and nutrients, including individual fatty acids and carotenoids. METHODS: Population-based case-control study of 858 men aged <70 years at diagnosis with histologically confirmed prostate cancer of Gleason Grade 5 or greater, and 905 age-frequency-matched men, selected at random from the electoral rolls. Dietary intakes were assessed with a 121-item food frequency questionnaire. RESULTS: Inverse associations with prostate cancer were observed for (Odds ratio, OR, 95% confidence intervals, 95% CI for tertile III compared with tertile I) allium vegetables 0.7, 0.5-0.9; p trend 0.01, tomato-based foods 0.8, 0.6-1.0; p trend 0.03 and total vegetables 0.7, 0.5-1.0; p trend 0.04. Margarine intake was positively associated with prostate cancer 1.3, 1.0-1.7; p trend 0.04. The only statistically significant associations observed with nutrients were weak inverse associations for palmitoleic acid ( p trend 0.04), fatty acid 17:1 ( p trend 0.04), and 20:5 n-6 ( p trend 0.05); and a non-significant trend for oleic acid ( p trend 0.09). Neither total, nor beverage-specific, intake of alcohol was associated with risk. CONCLUSIONS: Based on these findings, diets rich in olive oil (a source of oleic acid), tomatoes and allium vegetables might reduce the risk of prostate cancer.     

Association of NAT2 and smoking in relation to breast cancer incidence in a population-based case-control study (United States)

Objective: To evaluate the potential interaction between N-acetyltransferase 2 (NAT2) and smoking in breast cancer incidence. Methods: The data are derived from a population-based case–control study of women aged 20–69 years who were residents of Massachusetts or Wisconsin during 1997–1998. Incident cases of invasive breast cancer were identified through state tumor registries and age-similar controls were selected at random from population lists. Telephone interviews were conducted to obtain information on known and suspected risk factors including smoking history. Women provided oral mucosal DNA through the mail for genetic studies. Results: A total of 791 cases and 797 controls were included in the analysis. Overall, smoking was modestly associated with breast cancer risk (multivariate odds ratio (OR) for ever smoking: 1.37; 95% confidence interval (CI): 1.12–1.69), and there was a trend in risk for greater pack-years of smoking among postmenopausal women (p for trend = 0.02). Overall, NAT2 was not related to invasive breast cancer (multivariate OR: 1.11; 95% CI: 0.90–1.36). Associations of smoking with breast cancer tended to be somewhat stronger among the women with the slow acetylator genotype for NAT2: when compared to those who never smoked and were rapid acetylators, the OR for ever smoking was 1.50 (95% CI: 1.11–2.02) in slow acetylators, and OR: 1.24 (95% CI: 0.91–1.70) in rapid acetylators. However, tests for multiplicative interaction were not significant in case–control comparisons, or in case-only analyses. Conclusion: Results of the study are compatible with the majority of previous studies that indicate little or no association of NAT2, smoking, or their interaction with the occurrence of breast cancer.     

Adherence to nutrition‐based cancer prevention guidelines and breast,prostate and colorectal cancer risk in the MCC‐Spain case–control study

Prostate, breast and colorectal cancer are the most common tumours in Spain. The aim of the present study was to evaluate the association between adherence to nutrition‐based guidelines for cancer prevention and prostate, breast and colorectal cancer, in the MCC‐Spain case–control study. A total of 1,718 colorectal, 1,343 breast and 864 prostate cancer cases and 3,431 population‐based controls recruited between 2007 and 2012, were included in the present study. The World Cancer Research Fund/American Institute for Cancer Research (WCRC/AICR) score based on six recommendations for cancer prevention (on body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods and alcoholic drinks; score range 0–6) was constructed. We used unconditional logistic regression analysis adjusting for potential confounders. One‐point increment in the WCRF/AICR score was associated with 25% (95% CI 19–30%) lower risk of colorectal, and 15% (95% CI 7–22%) lower risk of breast cancer; no association with prostate cancer was detected, except for cases with a Gleason score ≥7 (poorly differentiated/undifferentiated tumours) (OR 0.87, 95% CI 0.76–0.99). These results add to the wealth of evidence indicating that a great proportion of common cancer cases could be avoided by adopting healthy lifestyle habits.     

Circulating enterolactone and risk of breast cancer: a prospective study in New York

It has been proposed that phyto-oestrogens protect against breast cancer. Lignans are the main class of phyto-oestrogens in Western diets. We conducted a case-control study of breast cancer and serum levels of the main human lignan, enterolactone, nested within a prospective cohort study, the New York University Women's Health Study. Serum samples collected at enrollment and stored at -80 degrees C were used. Among 14 275 participants, 417 incident breast cancer cases were diagnosed a median of 5.1 years after enrollment. Cohort members individually matched to the cases on age, menopausal status at enrollment, serum storage duration and, if premenopausal, day of menstrual cycle were selected as controls. No difference in serum enterolactone was observed between postmenopausal cases (median, 14.3 nmol l(-1)) and controls (14.5 nmol l(-1)), whereas premenopausal cases had higher levels (13.9 nmol l(-1)) than their matched controls (10.9 nmol l(-1), P-value=0.01). In the latter group, the odds ratio for the highest vs the lowest quintile of enterolactone was 1.7 (95% confidence interval (CI), 0.8-3.4; P-value for trend=0.05) and after adjustment for known risk factors for breast cancer was 1.6 (95% CI, 0.7-3.4; P-value for trend=0.13). We observed a moderate positive correlation between serum enterolactone and serum sex hormone-binding globulin in postmenopausal women (r=0.29 in controls (P<0.001) and r=0.14 in cases (P=0.04)), but no correlation with oestrogens or androgens. These results do not support a protective role of circulating lignans, in the range of levels observed, in the development of breast cancer.     

Fatherhood status and risk of prostate cancer: Nationwide,population‐based case–control study

Previous studies have shown a decreased risk of prostate cancer for childless men; however, the cause of the association remains to be elucidated. The aim of our study was to assess the risk of prostate cancer by fatherhood status, also considering potential confounding factors. In a case–control study in Prostate Cancer data Base Sweden 2.0, a nationwide, population‐based cohort, data on number of children, marital status, education, comorbidity and tumor characteristics obtained through nationwide healthcare registers and demographic databases for 117,328 prostate cancer cases and 562,644 controls, matched on birth year and county of residence, were analyzed. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for prostate cancer overall and by risk category, adjusting for marital status and education. Childless men had a decreased risk of prostate cancer compared to fathers, OR = 0.83 (95% CI = 0.82–0.84), and risk was lower for low‐risk prostate cancer, OR = 0.74 (95% CI = 0.72–0.77), than for metastatic prostate cancer, OR = 0.93 (95% CI = 0.90–0.97). Adjustment for marital status and education attenuated the association in the low‐risk category, adjusted OR = 0.87 (95% CI = 0.84–0.91), whereas OR for metastatic cancer remained virtually unchanged, adjusted OR = 0.92 (95% CI = 0.88–0.96). Our data indicate that the association between fatherhood status and prostate cancer to a large part is due to socioeconomic factors influencing healthcare‐seeking behavior including testing of prostate‐specific antigen levels.     

Antibiotic exposure and breast cancer in New Zealand

Summary Aims To investigate the hypothesis that use of antibiotics is related to subsequent development of breast cancer and also to apply this theory to other cancer types. Materials and methods A nested case–control study was conducted, using data linkage between the RNZCGP Research Unit database and the New Zealand Hospital Separation Diagnosis database. Cancer related hospital admissions were identified between 1998 and 2002, and prior antibiotic exposure in these patients was then found.Results A total of 6678 patients were identified with a newly diagnosed cancer in this time period. A slightly increased odds ratio (OR) (95% CI) for breast cancer was seen with penicillin, 1.07 (1.02–1.13). Penicillin was also associated with an increased OR with lung and respiratory cancer, 1.13 (1.06–1.21), and skin neoplasms, 1.05 (1.02–1.08). Significant associations were seen between macrolides and leukaemia, 1.15 (1.01–1.30), lung and respiratory cancers, 1.23 (1.10–1.38) and non-Hodgkin’s lymphoma, 1.26 (1.02–1.55). Tetracyclines were significantly associated with non-Hodgkin’s lymphoma, 1.12 (1.01–1.24). Cephalosporins only showed a significant association with leukaemia, 1.35 (1.06–1.71), sulphonamides with colorectal cancers, 1.12 (1.01–1.24), and ‘other‘ antibiotic classes with bladder and renal cancers, 1.34 (1.07–1.67). Conclusions It is most likely that antibiotic exposure represents a confounding factor rather than a causation for breast cancer and other cancer types.     

Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations

Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre‐diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case‐control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord‐Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow‐up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D₂ and 25(OH)D₃ combined] concentrations were determined using isotope‐dilution liquid chromatography‐tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42–1.20); 0.94 (0.72–1.22); 1.12 (0.82–1.53) and 1.26 (0.79–2.01) for clinically pre‐defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season‐standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre‐diagnostic concentrations of vitamin D, they are not statistically significant.     

Risk of prostate cancer associated with a family history in an era of rapid increase in prostate cancer diagnosis (Australia)

Objective: We conducted a case–control study of prostate cancer and familial risk of the disease in Australia between 1994 and 1998, a period during which the incidence of prostate cancer increased dramatically with widespread use of prostate-specific antigen (PSA) testing. Methods: 1475 cases and 1405 controls were asked about prostate cancer in their first-degree relatives. Odds ratios (OR) were calculated using logistic regression. Results: Cases were more likely to report a family history of prostate cancer than controls (OR 3.0; 95% confidence interval (CI) 2.3–3.9) and cases reporting an affected relative were younger (58.8 versus 60.9 years, p < 0.0001). The OR for an affected first-degree relative increased with increasing number of affected relatives and decreased with increasing age of the case. The OR for more than one affected first-degree relative was 6.9 (95% CI 2.7–18). The OR for an affected brother was 3.9 (95% CI 2.5–6.1) and for an affected father was 2.9 (95% CI 2.1–3.9) but these were not significantly different (p = 0.2). When analyses were repeated including only diagnoses made in relatives prior to 1992, the risks were generally similar except that the OR for an affected brother decreased to 3.1 (95% CI 1.2–3.9). When only relatives' diagnoses made after 1991 were included results were again similar to those for all relatives, although the effect for brothers was greater and the attenuation with age at diagnosis dissipated. Conclusions: The recent introduction of PSA testing that has resulted in a greater prevalence of apparent prostate cancer, does not appear to have substantially altered familial risks of disease, although effects associated with brothers may be inflated.     

Circulating enterolactone and prostate cancer risk: a Nordic nested case-control study

Enterolactone, a phytoestrogen belonging to the class of lignans, is produced by the intestinal microflora from precursors in plant foods and has been implicated in protection against cancer. We study the effect of enterolactone on the risk of a subsequent diagnosis of prostate cancer. We conducted a longitudinal, nested case-control study by linkage of 3 biobanks to the cancer registries in Finland, Norway and Sweden, respectively. Enterolactone concentrations were measured by time-resolved fluoroimmunoassay in serum from 794 men who had a diagnosis of prostate cancer at a mean follow-up time of 14.2 years after blood collection and among 2,550 control men matched within each cohort for age (+/-2 years), date of blood collection (+/-2 months) and county. The median enterolactone concentrations did not differ between case and control subjects in the full study group (8.4 nmol/L [25th-75th percentile = 4.5-15.0] vs. 8.5 nmol/L [25th-75th percentile = 4.3-15.9]), nor in the national groups. Odds ratios of prostate cancer risk estimated by conditional logistic regression for increasing concentrations of enterolactone in quartiles in the full study group were 1.00 (referent), 1.21 (95% confidence interval [CI] = 0.96-1.52), 1.16 (95% CI = 0.91-1.47) and 1.08 (95% CI = 0.83-1.39). The OR estimate for the highest vs. the lowest quartile of enterolactone in separate analyses of the Norwegian, Finnish and Swedish cohort was 1.21 (95% CI = 0.91-1.60), 1.02 (95% CI = 0.59-1.76) and 0.87 (95% CI = 0.45-1.67), respectively. No support for the hypothesis that high circulating enterolactone is protective against prostate cancer was found.     

Plasma prolactin and prostate cancer risk: A prospective study

Prolactin, a pituitary peptide hormone with multiple effects, stimulates prostate growth in experimental models. In humans, prolactin receptors are present in the prostate and are particularly abundant in pre-cancerous lesions. This suggests that prolactin could also be involved in the development of prostate cancer. In this study, we tested the hypothesis that elevated levels of circulating prolactin are associated with an increase in prostate cancer risk. We conducted a case-control study nested within the Northern Sweden Health and Disease Cohort using plasma samples collected from 29,560 men at a health survey. We measured prolactin in plasma from 144 men who had a diagnosis of prostate cancer after a median follow-up time of 4 years after health survey and from 289 controls matched for age and date of recruitment. Risk was not associated with plasma prolactin levels in univariate regression analysis. Odds ratios of prostate cancer for increasing quartiles of prolactin were 1.0, 0.92 (95% CI 0.51-1.65), 0.82 (0.45-1.51) and 0.85 (0.49-1.47). Relative risk estimates remained unchanged after adjustments for height and weight or for plasma levels of testosterone, sex hormone-binding globulin, IGF-I and IGF-binding protein-3. Elevated circulating levels of prolactin were not related to an increase in prostate cancer risk, indicating that high circulating prolactin is not associated with development of prostate cancer.