No effect of meat,meat cooking preferences,meat mutagens or heme iron on lung cancer risk in the prostate,lung, colorectal and ovarian cancer screening trial

Recent epidemiological studies have suggested that red and processed meat may increase the risk of lung cancer. Possible underlying mechanisms include mutagens produced during high‐temperature cooking or preservation, or formed endogenously from heme iron in meat. We used data from 99,579 participants of both screened and nonscreened arms of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, aged 55–74 years, to investigate whether meat type, cooking method, doneness level, intake of specific meat mutagens 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx), 2‐amino‐3,4,8‐trimethylimidazo[4,5‐f]quinoxaline] (DiMeIQx), 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and benzo(a)pyrene (B(a)P)] and heme iron are associated with lung cancer. Participants' diet was assessed prospectively using a 124‐item food frequency questionnaire and an additional meat‐cooking module. Dietary data were used in conjunction with a database to estimate intake of MeIQx, DiMeIQx, PhIP, B(a)P and heme iron. After up to 8 years of follow‐up, 782 incident lung cancer cases were ascertained. Lung cancer risk was not associated with the consumption of either red (men: HR_{Q5 vs. Q1} = 1.11, 95% CI = 0.79–1.56, P_trend = 0.42; women: HR_{Q5 vs. Q1} = 1.30, 95% CI = 0.87–1.95, P_trend = 0.65) or processed meat (men: HR_{Q5 vs. Q1} = 1.12, 95% CI = 0.83–1.53, P_trend = 0.22; women: HR_{Q5 vs. Q1} = 0.98, 95% CI = 0.68–1.41, P_trend = 0.32) in multivariable models. High‐temperature cooking methods, level of meat doneness, meat mutagens and heme iron had no effect on lung cancer risk. In this population, we found no association between meat type, cooking method, doneness level or intake of specific meat mutagens or heme iron and lung cancer risk.     

Issues with implementing a high‐quality lung cancer screening program

Answer questions and earn CME/CNE After a comprehensive review of the evidence, the United States Preventive Services Task Force recently endorsed screening with low‐dose computed tomography as an early detection approach that has the potential to significantly reduce deaths due to lung cancer. Prudent implementation of lung cancer screening as a high‐quality preventive health service is a complex challenge. The clinical evaluation and management of high‐risk cohorts in the absence of symptoms mandates an approach that differs significantly from that of symptom‐detected lung cancer. As with other cancer screenings, it is essential to provide to informed at‐risk individuals a safe, high‐quality, cost‐effective, and accessible service. In this review, the components of a successful screening program are discussed as we begin to disseminate lung cancer screening as a national resource to improve outcomes with this lethal cancer. This information about lung cancer screening will assist clinicians with communications about the potential benefits and harms of this service for high‐risk individuals considering participation in the screening process. CA Cancer J Clin 2014;64:351–363. © 2014 American Cancer Society.     

结直肠镜漏诊结直肠癌情况一致性的评价研究

目的  利用美国前列腺、肺、结直肠及卵巢癌筛查数据库（prostate,lung,colorectal,and ovarian,PLCO）,评价结直肠镜漏诊结直肠癌的比例及漏诊病人的特征,为提高结直肠癌的筛查效果提供循证依据。 方法  选择PLCO研究干预人群中进行了基线检查或者3年或5年结直肠镜复查的结直肠癌病人为研究对象。以基线或者随访结直肠镜检查没发现的结直肠癌患者为分子,以基线或者随访结直肠镜检查一年内发现的所有结直肠癌患者（结直肠镜发现的结直肠癌患者+肿瘤登记系统发现的结直肠癌患者+年度自我报告问卷发现的结直肠癌患者）为分母,计算结直肠镜漏诊结直肠癌的比例。 结果  共有338名结直肠癌患者纳入分析,其中经结直肠镜检查漏诊59名,漏诊比例为17.5%。65~69岁的漏诊率相对较高（24.2%）、低分化和近端结肠癌漏诊比例较高（32.4%和47.4%）。 结论  结直肠镜检查漏诊结直肠癌的比例相对较高,漏诊主要集中在近端结肠,提高粪便DNA等检测技术的准确性,可能是克服结直肠镜漏诊问题的有效途径。     

Prospective study of the relationship between coffee and tea with colorectal cancer risk: The PLCO Cancer Screening Trial

Background:

Coffee and tea are commonly consumed and carry potential anticancer components that could reduce the risk of colorectal cancer; however, their relationships with colorectal cancer risk remain inconsistent.

Methods:

A prospective analysis was carried out to examine the relationships of coffee and tea intake with colorectal cancer risk in 57 398 men and women in the intervention arm of the National Cancer Institute-Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, a national screening study that limits differential detection biases. Coffee and tea intakes were assessed by food frequency questionnaire.

Results:

Six hundred and eighty-one incident colorectal cancer cases were ascertained during a median follow-up of 11.4 years. Greater coffee intake was not associated with risk of colorectal cancer (relative risk (RR)=1.08, 95% confidence interval (CI)=0.79–1.48, P_trend=0.23). Stratifying by cancer site (P_{heterogeneity}=0.48) or stage (P_{heterogeneity}=0.83) did not alter the relationship. Associations remained unchanged in subsets of participants for either caffeinated or decaffeinated coffee or when stratifying by several colorectal cancer risk factors. Similarly, greater tea intake was not associated with colorectal cancer risk overall (RR=0.77, 95% CI=0.55–1.09, P_trend=0.17) or by cancer site (P_{heterogeneity}=0.14) or stage (P_{heterogeneity}=0.60). These associations were not modified by several colorectal cancer risk factors.

Conclusion:

The findings of this study do not provide evidence to suggest that drinking coffee or tea is beneficial in protecting against colorectal cancer.     

Potential effect of the risk of ovarian cancer algorithm (ROCA) on the mortality outcome of the Prostate,Lung, Colorectal and Ovarian (PLCO) trial

Recently, the Prostate, Lung, Colorectal and Ovarian (PLCO) Trial reported no mortality benefit for annual screening with CA‐125 and transvaginal ultrasound (TVU). Currently ongoing is the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), which utilizes the risk of ovarian cancer algorithm (ROCA), a statistical tool that considers current and past CA125 values to determine ovarian cancer risk. In contrast, PLCO used a single cutoff for CA125, based on current levels alone. We investigated whether having had used ROCA in PLCO could have, under optimal assumptions, resulted in a significant mortality benefit by applying ROCA to PLCO CA125 screening values. A best‐case scenario assumed that all cancers showing a positive screen result earlier with ROCA than under the PLCO protocol would have avoided mortality; under a stage‐shift scenario, such women were assigned survival equivalent to Stage I/II screen‐detected cases. Updated PLCO data show 132 intervention arm ovarian cancer deaths versus 119 in usual care (relative risk, RR = 1.11). Forty‐three ovarian cancer cases, 25 fatal, would have been detected earlier with ROCA, with a median (minimum) advance time for fatal cases of 344 (147) days. Best‐case and stage‐shift scenarios gave 25 and 19 deaths prevented with ROCA, for RRs of 0.90 (95% CI: 0.69–1.17) and 0.95 (95% CI: 0.74–1.23), respectively. Having utilized ROCA in PLCO would not have led to a significant mortality benefit of screening. However, ROCA could still show a significant effect in other screening trials, including UKCTOCS.     

Abnormal CA-125 levels in menopausal women without ovarian cancer

Objective

To determine if an abnormal CA-125 level in a menopausal female without ovarian cancer is associated with an increase in mortality.

Methods

The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Randomized Controlled (PLCO) Trial is a large multicenter prospective trial conducted by the National Cancer Institute (NCI). Over 78,000 healthy women aged 55–74 were randomized to a screening arm versus a usual medical care arm to evaluate the efficacy of screening in reducing mortality due to ovarian cancer. Women in the screening arm underwent annual screening for ovarian cancer with transvaginal ultrasound and CA-125 levels. There were 38,818 patients without ovarian cancer that had at least one CA-125 level drawn; 1201 (3.09%) had at least one abnormal level. The current study compares mortality in patients that had one or more abnormal CA-125 levels without ovarian cancer versus those with all normal levels.

Results

Patients with one or more abnormal CA-125 levels, without ovarian cancer, had a significantly higher mortality than patients with all normal CA-125 levels in the PLCO screening trial (p < 0.0001). This increased risk extended throughout the follow-up period. Analysis of cause of death listed on the death certificate showed an excess mortality attributable to lung cancer, digestive disease, and endocrine, nutritional, and metabolic disease.

Conclusion

Menopausal females with an elevated CA-125 and without ovarian cancer are exposed to an increased risk of premature mortality.