Nea Malila

Diet and risk of colorectal cancer in a cohort of Finnish men

Objectives: Based on previous epidemiological studies, high fat and meat consumption may increase and fiber, calcium, and vegetable consumption may decrease the risk of colorectal cancer. We sought to address these hypotheses in a male Finnish cohort.Methods: We analyzed data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) where 27, 111 male smokers completed a validated dietary questionnaire at baseline. After an average of 8 years of follow-up, we documented 185 cases of colorectal cancer. The analyses were carried out using the Cox proportional hazards model.Results: The relative risk (RR) for men in the highest quartile of calcium intake compared with men in the lowest quartile was 0.6 (95% CI 0.4–0.9, p for trend 0.04). Likewise, the intake of milk protein and the consumption of milk products was inversely associated with risk of colorectal cancer. However, intake of dietary fiber was not associated with risk, nor was fat intake. Consumption of meat or different types of meat, and fried meat, fruits or vegetables were not associated with risk.Conclusions: In this cohort of men consuming a diet high in fat, meat, and fiber and low in vegetables, high calcium intake was associated with lowered risk of colorectal cancer.

Age-specific evaluation of primary human papillomavirus screening vs conventional cytology in a randomized setting.

BACKGROUND Human papillomavirus (HPV) DNA testing has shown higher sensitivity than cytology for detecting cervical lesions, but it is uncertain whether the higher sensitivity is dependent on the age of the woman being screened. We compared the age-specific performance of primary HPV DNA screening with that of conventional cytology screening in the setting of an organized population-based cervical cancer screening program in Finland. METHODS From January 1, 2003, to December 31, 2005, randomized invitations were sent to women aged 25-65 years for routine cervical cancer screening by primary high-risk HPV DNA testing (n = 54 207) with a Hybrid Capture 2 assay followed by cytology triage for women who were HPV DNA positive or by conventional cytology screening (n = 54 218). In both screening arms, cytology results of low-grade squamous intraepithelial lesion or worse triggered a referral for colposcopy. Relative rates (RRs) of detection to assess test sensitivity, specificity, and positive predictive values (PPVs) with 95% confidence intervals (CIs) were calculated for the histological endpoints of cervical intraepithelial neoplasia (CIN) grade 1 or higher (CIN 1+), CIN grade 2 or higher (CIN 2+), and CIN grade 3 or higher (CIN 3+). All statistical tests were two-sided. RESULTS The overall frequency of colposcopy referrals was 1.2% in both screening arms. Women younger than 35 years were referred more often in the HPV DNA screening vs the conventional screening arm (RR = 1.27, 95% CI = 1.01 to 1.60). The prevalence of histologically confirmed CIN or cancer was 0.59% in the HPV DNA screening arm vs 0.43% in the conventional screening arm. The relative rates of detection for CIN 1, CIN 2, and CIN 3+ for HPV DNA screening with cytology triage vs conventional screening were 1.44 (95% CI = 0.99 to 2.10), 1.39 (95% CI = 1.03 to 1.88), and 1.22 (95% CI = 0.78 to 1.92), respectively. The specificity of the HPV DNA test with cytology triage was equal to that of conventional screening for all age groups (99.2% vs 99.1% for CIN 2+, P = .13). Among women aged 35 years or older, the HPV DNA test with cytology triage tended to have higher specificity than conventional screening. The PPVs for HPV DNA screening with cytology triage were consistently higher than those for conventional screening. In both screening arms, the test specificities increased with increasing age of the women being screening, whereas the highest PPVs were observed among the youngest women being screened. Overall, 7.2% of women in the HPV DNA screening arm vs 6.6% of women in the conventional screening arm were recommended for intensified follow-up, and the percentages were highest among 25- to 29-year-olds (21.9% vs 10.0%, respectively). CONCLUSIONS Primary HPV DNA screening with cytology triage is more sensitive than conventional screening. Among women aged 35 years or older, primary HPV DNA screening with cytology triage is also more specific than conventional screening and decreases colposcopy referrals and follow-up tests.

Effects of supplemental α-tocopherol and β-carotene on colorectal cancer: results from a controlled trial (Finland)

AbstractBackground:Some epidemiological investigations suggest that higher intake or biochemical status of vitamin E and β-carotene might be associated with reduced risk of colorectal cancer. Methods:We tested the effects of α-tocopherol and β-carotene supplementation on the incidence of colorectal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, placebo-controlled trial among 29,133 50–69-year-old male cigarette smokers. Participants were randomly assigned to receive α-tocopherol (50 mg), β-carotene (20 mg), both agents, or a placebo daily for 5–8 years. Incident colorectal cancers (n = 135) were identified through the nationwide cancer registry, and 99% were histologically confirmed. Intervention effects were evaluated using survival analysis and proportional hazards models. Results:Colorectal cancer incidence was somewhat lower in the α-tocopherol arm compared to the no α-tocopherol arm, but this finding was not statistically significant (relative risk (RR) = 0.78, 95% confidence interval (CI) 0.55–1.09; log-rank test p = 0.15). β-Carotene had no effect on colorectal cancer incidence (RR=1.05, 95% CI 0.75–1.47; log-rank test p = 0.78). There was no interaction between the two substances. Conclusion:Our study found no evidence of a beneficial or harmful effect for β-carotene in colorectal cancer in older male smokers, but does provide suggestive evidence that vitamin E supplementation may have had a modest preventive effect. The latter finding is in accord with previous research linking higher vitamin E status to reduced colorectal cancer risk.

Rate of cervical cancer, severe intraepithelial neoplasia, and adenocarcinoma in situ in primary HPV DNA screening with cytology triage: randomised study within organised screening programme

Objective To assess the performance and impact of primary human papillomavirus (HPV) DNA screening with cytology triage compared with conventional cytology on cervical cancer and severe pre-cancerous lesions. Design Randomised trial. Setting Population based screening programme for cervical cancer in southern Finland in 2003-5. Participants 58 076 women, aged 30-60, invited to the routine population based screening programme for cervical cancer. Interventions Primary HPV DNA test (hybrid capture II) with cytology triage if the result was positive or conventional cytological screening (reference). Main outcome measures Rate of cervical cancer, cervical intraepithelial neoplasia (CIN) grade III, and adenocarcinoma in situ (as a composite outcome referred to as CIN III+) during 2003-7 through record linkage between files from the screening registry and the national cancer registry. Results In the HPV and conventional arms there were 95 600 and 95 700 woman years of follow-up and 76 and 53 cases of CIN III+, respectively (of which six and eight were cervical cancers). The relative rate of CIN III+ in the HPV arm versus the conventional arm was 1.44 (95% confidence interval 1.01 to 2.05) among all women invited for screening and 1.77 (1.16 to 2.74) among those who attended. Among women with a normal or negative test result, the relative rate of subsequent CIN III+ was 0.28 (0.04 to 1.17). The rate of cervical cancer between arms was 0.75 (0.25 to 2.16) among women invited for screening and 1.98 (0.52 to 9.38) among those who attended. Conclusions When incorporated into a well established organised screening programme, primary HPV screening with cytology triage was more sensitive than conventional cytology in detecting CIN III+ lesions. The number of cases of cervical cancer was small, but considering the high probability of progression of CIN III the findings are of importance regarding cancer prevention. Trial registration Current Controlled Trials ISRCTN23885553.

Diet and prostate cancer risk in a cohort of smokers, with a specific focus on calcium and phosphorus (Finland)

AbstractBackground:Calcium, phosphorus, fructose, and animal protein are hypothesized to be associated with prostate cancer risk, potentially via their influence on 1,25-dihydroxyvitamin D3. We examined these nutrients and overall diet and prostate cancer risk in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC Study). Materials and methods:The ATBC Study was a randomized 2 × 2 trial of alpha-tocopherol and beta-carotene on lung cancer incidence conducted among Finnish male smokers; 27,062 of the men completed a food-use questionnaire at baseline, and comprise the current study population. There were 184 incident clinical (stage 2–4) prostate cancer cases diagnosed between 1985 and 1993. We used Cox proportional hazards models to examine associations between dietary intakes and prostate cancer. Results:We did not observe significant independent associations for calcium and phosphorus and prostate cancer risk. However, men with lower calcium and higher phosphorus intake had a multivariate relative risk of 0.6 (95% CI 0.3–1.0) compared to men with lower intakes of both nutrients, adjusting for age, smoking, body mass index, total energy, education, and supplementation group. Of the other foods and nutrients examined, none was significantly associated with risk. Discussion:This study provides, at best, only weak evidence for the hypothesis that calcium and phosphorus are independently associated with prostate cancer risk, but suggests that there may be an interaction between these nutrients.

Probability of parenthood after early onset cancer: a population-based study.

We evaluated in a population‐based setting the postdiagnosis parenthood among survivors compared with the fertility patterns of siblings. Cancer patients aged 0–34 years at diagnosis were identified from the Finnish Cancer Registry (N = 25,784), and their siblings (N = 44,611) by registry linkage. Further linkage identified the offspring of the patient and sibling cohorts. The relative probabilities of parenthood for first and second births separately were estimated for male and female survivors in different diagnostic age‐groups and subsites using a Cox proportional hazards model, with age as the time variable and adjusting for the birth cohort of parents. In addition, estimates were calculated for 5 diagnostic eras in all subsites combined. Compared to siblings, both female and male cancer survivors were less likely to parent at least 1 child (RR 0.46, 95% CI 0.44–0.48 and RR 0.57, 95% CI 0.54–0.60, respectively). The relative probability of parenthood was especially low in male childhood cancer survivors and female young adult cancer survivors. However, cancer patients were only slightly less likely than siblings to parent a second child, with RR 0.91, 95% CI 0.86–0.97 and RR 0.95, 95% CI 0.89–1.01 for females and males, respectively. The relative probability of parenthood increased over calendar time among young adult cancer patients. The relative probability of parenthood following early onset cancer was overall significantly reduced by ∼50%. Parenting a second child, however, was not reduced among pediatric and adolescent survivors, and only slightly reduced among early adulthood cancer survivors compared to siblings.

Effects of supplemental alpha-tocopherol and beta-carotene on urinary tract cancer: incidence and mortality in a controlled trial (Finland)

AbstractObjectives: Epidemiological studies have suggested a protective effect of vegetables and fruits on urinary tract cancer but the possible protective nutrients are unknown. We studied the effect of alpha-tocopherol (a form of vitamin E) and beta-carotene supplementation on urinary tract cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Methods: A total of 29,133 male smokers aged 50–69 years from southwestern Finland were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or a placebo daily for 5–8 years (median 6.1 years). Incident urothelial cancers (bladder, ureter, and renal pelvis; n = 169) and renal cell cancers (n = 102) were identified through the nationwide cancer registry. The diagnoses were centrally confirmed by review of medical records and pathology specimens. The supplementation effects were estimated using a proportional hazards model. Results: Neither alpha-tocopherol nor beta-carotene affected the incidence of urothelial cancer, relative risk 1.1 (95% confidence interval (CI) 0.8–1.5) and 1.0 (95% CI 0.7–1.3), respectively, or the incidence of renal cell cancer, relative risk 1.1 (95% CI 0.7–1.6) and 0.8 (95% CI 0.6–1.3), respectively. Conclusion: Long-term supplementation with alpha-tocopherol and beta-carotene has no preventive effect on urinary tract cancers in middle-aged male smokers.

Prostate Cancer Mortality in the Finnish Randomized Screening Trial

BACKGROUND Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality by the European Randomized Study of Screening for Prostate Cancer (ERSPC). We evaluated mortality results in the Finnish Prostate Cancer Screening Trial, the largest component of ERSPC. The primary endpoint was PC-specific mortality. METHODS A total of 80 144 men were identified from the population registry and randomized to either a screening arm (SA) or a control arm (CA). Men in the SA were invited to serum PSA determination up to three times with a 4-year interval between each scan and referred to biopsy if the PSA concentration was greater than or equal to 4.0 ng/mL or 3.0 to 3.99 ng/mL with a free/total PSA ratio less than or equal to 16%. Men in the CA received usual care. The analysis covers follow-up to 12 years from randomization for all men. Hazard ratios (HRs) were estimated for incidence and mortality using Cox proportional hazard model. All statistical tests were two-sided. RESULTS PC incidence was 8.8 per 1000 person-years in the SA and 6.6 in the CA (HR = 1.34, 95% confidence interval [CI] = 1.27 to 1.40). The incidence of advanced PC was lower in the SA vs CA arm (1.2 vs 1.6, respectively; HR = 0.73, 95% CI = 0.64 to 0.82; P < .001). For PC mortality, no statistically significant difference was observed between the SA and CA (HR = 0.85, 95% CI = 0.69 to 1.04) (with intention-to-screen analysis). To avoid one PC death, we needed to invite 1199 men to screening and to detect 25 PCs. We observed no difference in all-cause mortality between trial arms. CONCLUSIONS At 12 years, a relatively conservative screening protocol produced a small, non-statistically significant PC-specific mortality reduction in the Finnish trial, at the cost of moderate overdiagnosis.

Tea and coffee consumption and risk of colon and rectal cancer in middle-aged Finnish men

The association between coffee and black tea consumption and the subsequent risk of colon and rectal cancer was investigated within a Finnish clinical trial cohort. One hundred eleven cases of colon cancer and 83 cases of rectal cancer were diagnosed over a median of 9.0 years of follow-up. Proportional hazards regression models were used to derive adjusted relative risk (RR) and 95% confidence intervals (CI) for the association between coffee and tea consumption and cancer incidence. After controlling for confounders, coffee was not significantly associated with colon or rectal cancer. A positive association was seen for increased consumption of tea drinking and colon cancer. Compared with persons who did not drink tea, those who consumed <1 cup/day had an RR of 1.40 (95% CI = 0.84 - 2.33) and those who consumed > or = 1 cup/day had an RR of 2.09 (95% CI = 1.34-3.26, p for trend = 0.001). In contrast, tea consumption had little effect on rectal cancer incidence. This study does not support the hypothesis that coffee and tea protect against colorectal cancer risk. However, given the strength of the tea-colon cancer association and the significant gradient of risk we observed across level of intake, further epidemiologic research of this relationship in other populations seems warranted.

Test, episode, and programme sensitivities of screening for colorectal cancer as a public health policy in Finland: experimental design

Objectives To report the sensitivities of the faecal occult blood test, screening episode, and screening programme for colorectal cancer and the benefits of applying a randomised design at the implementation phase of a new public health policy. Design Experimental design incorporated in public health evaluation using randomisation at individual level in the target population. Setting 161 of the 431 Finnish municipalities in 2004-6. Participants 106 000 adults randomised to screening or control arms. In total, 52 998 adults aged 60-64 in the screening arm received faecal occult blood test kits. Main outcome measures Test, episode, and programme sensitivities estimated by the incidence method and corrected for selective attendance and overdiagnosis. Results The response for screening was high overall (70.8%), and significantly better in women (78.1%) than in men (63.3%). The incidence of cancer in the controls was somewhat higher in men than in women (103 v 93 per 100 000 person years), which was not true for interval cancers (42 v 49 per 100 000 person years). The sensitivity of the faecal occult blood test was 54.6%. Only a few interval cancers were detected among those with positive test results, hence the episode sensitivity of 51.3% was close to the test sensitivity. At the population level the sensitivity of the programme was 37.5%. Conclusions Although relatively low, the sensitivity of screening for colorectal cancer with the faecal occult blood test in Finland was adequate. An experimental design is a prerequisite for evaluation of such a screening programme because the effectiveness of preventing deaths is likely to be small and results may otherwise remain inconclusive. Thus, screening for colorectal cancer using any primary test modality should be launched in a public health programme with randomisation of the target population at the implementation phase.