Inger Torhild Gram

Quality of life following a false positive mammogram

To assess how women regard having had a false positive mammogram screening exam, and the influence that this had on their quality of life, 126 such women were interviewed. Their responses were compared to those of 152 women randomly selected among screenees with a negative exam. Eighteen months after the screening the reported prevalence of anxiety about breast cancer was 29% among women with a false positive and 13% among women with a negative screening mammogram (P = 0.001). Of 30 women biopsied, 8 (27%) had pain in the breast and 10 (33%) had reduced sexual sensitivity. A false positive mammogram was described by 7 (5%) of the women as the worst thing they ever had experienced. However, most women with a false positive result regarded this experience, in retrospect, as but one of many minor stressful experiences creating a temporary decrease in quality of life. They report the same quality of life today as women with negative screening results and 98% would attend another screening. Even so, false positive results are a matter of concern, and efforts should be made to minimise this cost whenever a screening programme is conducted.

The Tabár classification of mammographic parenchymal patterns.

The purpose of this study was to describe one method of classification, based on anatomic-mammographic correlations, developed by Tabár. We also wanted to examine how the mammograms categorized as low- and high-risk according to Tabár and Wolfe criteria related to each other and to three selected risk factors for breast cancer. The study materials are based on questionnaires and mammograms from 3,640 Norwegian women, aged 40-56 years, participating in the third Tromsö study. The mammograms were categorized into five groups. Line drawings and their pathologic correlates of the five patterns are described in detail. The Tabár classification is based on anatomic-mammographic correlations, following three-dimensional (thick slice technique) histopathologic-mammographic comparisons, rather than simple pattern reading (Wolfe classification). For analysis patterns I-III (Tabár) and N1 and P1 (Wolfe) were grouped into low-risk groups and patterns IV and V (Tabár) and P2 and DY Wolfe) into high-risk groups. The overall agreement on high-risk versus low risk for the two classifications was 54% with a kappa-value of 0.22. The study displays that the strength of association between high-risk mammographic patterns and the three selected risk factors parity, number of children and age at first birth is of greater magnitude when the Tabár instead of the Wolfe classification is applied. More patients are needed to compare the classification directly with the risk of cancer. This study indicates that further development of the classification of mammograms may increase the usefulness of mammographic patterns in research and clinical practice.

Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies.

Several prospective studies have shown a moderate positive association between increasing circulating insulin‐like growth factor‐I (IGF‐I) levels and colorectal cancer risk. However, the associations were often statistically nonsignificant, and the relationship of cancer risk with IGF‐Is major binding protein, IGFBP‐3, showed major discrepancies between studies. We investigated the association of colorectal cancer risk with serum IGF‐I, total and intact IGFBP‐3, in a case‐control study nested within the EPIC cohort (1,121 cases of colorectal cancer and 1,121 matched controls). Conditional logistic regression was used to adjust for possible confounders. Our present study results were combined in a meta‐analysis with those from 9 previous prospective studies to examine the overall evidence for a relationship of prediagnostic serum IGF‐I with colorectal cancer risk. In the EPIC study, serum concentrations of IGF‐I and IGFBP‐3 showed no associations with risk of colorectal cancer overall. Only in subgroup analyses did our study show moderate positive associations of IGF‐I levels with risk, either among younger participants only (and only for colon cancer) or among participants whose milk intakes were in the lowest tertile of the population distribution (RR for an increase of 100 ng/ml = 1.43 [95% CI = 1.13–1.93]). Nevertheless, in the meta‐analysis a modest positive association remained between serum IGF‐I and colorectal cancer risk overall (RR = 1.07 [1.01–1.14] for 1 standard deviation increase in IGF‐I). Overall, data from our present study and previous prospective studies combined indicate a relatively modest association of colorectal cancer risk with serum IGF‐I.

Fruits and vegetables and lung cancer: Findings from the European prospective investigation into cancer and nutrition

Intake of fruits and vegetables is thought to protect against the development of lung cancer. However, some recent cohort and case‐control studies have shown no protective effect. We have assessed the relation between fruit and vegetable intake and lung cancer incidence in the large prospective investigation on diet and cancer, the European Prospective Investigation Into Cancer and Nutrition (EPIC). We studied data from 478,021 individuals that took part in the EPIC study, who were recruited from 10 European countries and who completed a dietary questionnaire during 1992–1998. Follow‐up was to December 1998 or 1999, but for some centres with active follow‐up to June 2002. During follow‐up, 1,074 participants were reported to have developed lung cancer, of whom 860 were eligible for our analysis. We used the Cox proportional hazard model to determine the effect of fruit and vegetable intake on the incidence of lung cancer. We paid particular attention to adjustment for smoking. Relative risk estimates were obtained using fruit and vegetable intake categorised by sex‐specific, cohort‐wide quintiles. After adjustment for age, smoking, height, weight and gender, there was a significant inverse association between fruit consumption and lung cancer risk: the hazard ratio for the highest quintile of consumption relative to the lowest being 0.60 (95% Confidence Interval 0.46–0.78), p for trend 0.0099. The association was strongest in the Northern Europe centres, and among current smokers at baseline, and was strengthened when the 293 lung cancers diagnosed in the first 2 years of follow‐up were excluded from the analysis. There was no association between vegetable consumption or vegetable subtypes and lung cancer risk. The findings from this analysis can be regarded as re‐enforcing recommendations with regard to enhanced fruit consumption for populations. However, the effect is likely to be small compared to smoking cessation.

Cervical carcinoma and reproductive factors: Collaborative reanalysis of individual data on 16,563 women with cervical carcinoma and 33,542 women without cervical carcinoma from 25 epidemiological studies.

The International Collaboration of Epidemiological Studies of Cervical Cancer has combined individual data on 11,161 women with invasive carcinoma, 5,402 women with cervical intraepithelial neoplasia (CIN)3/carcinoma in situ and 33,542 women without cervical carcinoma from 25 epidemiological studies. Relative risks (RRs) and 95% confidence intervals (CIs) of cervical carcinoma in relation to number of full‐term pregnancies, and age at first full‐term pregnancy, were calculated conditioning by study, age, lifetime number of sexual partners and age at first sexual intercourse. Number of full‐term pregnancies was associated with a risk of invasive cervical carcinoma. After controlling for age at first full‐term pregnancy, the RR for invasive cervical carcinoma among parous women was 1.76 (95% CI: 1.53–2.02) for ≥≥7 full‐term pregnancies compared with 1–2. For CIN3/carcinoma in situ, no significant trend was found with increasing number of births after controlling for age at first full‐term pregnancy among parous women. Early age at first full‐term pregnancy was also associated with risk of both invasive cervical carcinoma and CIN3/carcinoma in situ. After controlling for number of full‐term pregnancies, the RR for first full‐term pregnancy at age <17 years compared with ≥≥25 years was 1.77 (95% CI: 1.42–2.23) for invasive cervical carcinoma, and 1.78 (95% CI: 1.26–2.51) for CIN3/carcinoma in situ. Results were similar in analyses restricted to high‐risk human papilloma virus (HPV)‐positive cases and controls. No relationship was found between cervical HPV positivity and number of full‐term pregnancies, or age at first full‐term pregnancy among controls. Differences in reproductive habits may have contributed to differences in cervical cancer incidence between developed and developing countries.

Fruit and vegetable consumption and lung cancer risk: updated information from the European Prospective Investigation into Cancer and Nutrition (EPIC).

The association of fruit and vegetable consumption and lung cancer incidence was evaluated using the most recent data from the European Prospective Investigation into Cancer and Nutrition (EPIC), applying a refined statistical approach (calibration) to account for measurement error potentially introduced by using food frequency questionnaire data. Between 1992 and 2000, detailed information on diet and life‐style of 478,590 individuals participating in EPIC was collected. During a median follow‐up of 6.4 years, 1,126 lung cancer cases were observed. Multivariate Cox proportional hazard models were applied for statistical evaluation. In the whole study population, fruit consumption was significantly inversely associated with lung cancer risk while no association was found for vegetable consumption. In current smokers, however, lung cancer risk significantly decreased with higher vegetable consumption; this association became more pronounced after calibration, the hazard ratio (HR) being 0.78 (95% CI 0.62–0.98) per 100 g increase in daily vegetable consumption. In comparison, the HR per 100 g fruit was 0.92 (0.85–0.99) in the entire cohort and 0.90 (0.81–0.99) in smokers. Exclusion of cases diagnosed during the first 2 years of follow‐up strengthened these associations, the HR being 0.71 (0.55–0.94) for vegetables (smokers) and 0.86 (0.78–0.95) for fruit (entire cohort). Cancer incidence decreased with higher consumption of apples and pears (entire cohort) as well as root vegetables (smokers). In addition to an overall inverse association with fruit intake, the results of this evaluation add evidence for a significant inverse association of vegetable consumption and lung cancer incidence in smokers.

The Association between Diet and Serum Concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in the European Prospective Investigation into Cancer and Nutrition

Circulating concentrations of insulin-like growth factor I (IGF-I) and IGF binding proteins (IGFBP) have been associated with the risk of several types of cancer. Dietary correlates of IGF-I and IGFBPs are not yet well established. The objective of this study was to assess the association between dietary intake and serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in a cross-sectional analysis of 4,731 men and women taking part in the European Prospective Investigation into Cancer and Nutrition. Diet was assessed using country-specific validated dietary questionnaires. Serum concentrations of IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3 were measured, and the associations between diet and IGF-I and IGFBPs were assessed using multiple linear regression adjusting for sex, age, body mass index, smoking status, and alcohol and energy intake. Each 1 SD increment increase in total and dairy protein and calcium intake was associated with an increase in IGF-I concentration of 2.5%, 2.4%, and 3.3%, respectively (P for trend <0.001 for all) and a decrease in IGFBP-2 of 3.5%, 3.5%, and 5.4% (P for trend <0.001 for all), respectively. There were no significant associations between the intake of protein or calcium from nondairy sources and IGF-I. The results from this large cross-sectional analysis show that either the intake of dairy protein or calcium is an important dietary determinant of IGF-I and IGFBP-2 concentrations; however, we suggest that it is more likely to be protein from dairy products. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1333–40)

Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition

Background:It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear.Methods:We examined the associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327 396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use.Results:Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41–0.75) lower risk compared with users of 1 year or less (P-trend, <0.01). Compared with nulliparous women, parous women had a 29% (HR, 0.71; 95% CI, 0.59–0.87) lower risk, with an 8% reduction in risk for each additional pregnancy. A high age at menopause was associated with a higher risk of ovarian cancer (>52 vs ⩽45 years: HR, 1.46; 95% CI, 1.06–1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk.Conclusion:This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors.

Cigarette smoking, environmental tobacco smoke exposure and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition

Cigarette smoking is an established risk factor for pancreatic cancer. However, prospective data for most European countries are lacking, and epidemiologic studies on exposure to environmental tobacco smoke (ETS) in relation to pancreatic cancer risk are scarce. We examined the association of cigarette smoking and exposure to ETS with pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). This analysis was based on 465,910 participants, including 524 first incident pancreatic cancer cases diagnosed after a median follow‐up of 8.9 years. Estimates of risk were obtained by Cox proportional hazard models and adjusted for weight, height, and history of diabetes mellitus. An increased risk of pancreatic cancer was found for current cigarette smokers compared with never smokers (HR = 1.71, 95% CI = 1.36–2.15), and risk increased with greater intensity and pack‐years. Former cigarette smokers who quit for less than 5 years were at increased risk of pancreatic cancer (HR = 1.78, 95% CI = 1.23–2.56), but risk was comparable to never smokers after quitting for 5 years or more. Pancreatic cancer risk was increased among never smokers daily exposed to ETS (for many hours) during childhood (HR = 2.61, 95% CI = 0.96–7.10) and exposed to ETS at home and/or work (HR = 1.54, 95% CI = 1.00–2.39). These results suggest that both active cigarette smoking, as well as exposure to ETS, is associated with increased risk of pancreatic cancer and that risk is reduced to levels of never smokers within 5 years of quitting.

Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer.

Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however, there are little data on the role of obesity‐related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intrahepatic bile duct (IBD), and gallbladder and biliary tract cancers outside of the liver (GBTC) in a nested case‐control study within the European Prospective Investigation into Cancer and Nutrition. Over an average of 7.7 years, 296 participants developed HCC (n = 125), GBTC (n = 137), or IBD (n = 34). Using risk‐set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, and time of blood collection. Baseline serum concentrations of C‐reactive protein (CRP), interleukin‐6 (IL‐6), C‐peptide, total high‐molecular‐weight (HMW) adiponectin, leptin, fetuin‐a, and glutamatdehydrogenase (GLDH) were measured, and incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection, and adiposity measures, higher concentrations of CRP, IL‐6, C‐peptide, and non‐HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95% CI = 1.02‐1.46; P = 0.03; 1.90; 95% CI = 1.30‐2.77; P = 0.001; 2.25; 95% CI = 1.43‐3.54; P = 0.0005; and 2.09; 95% CI = 1.19‐3.67; P = 0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95% CI = 1.05‐1.42; P = 0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95% CI = 1.25‐2.11; P = 0.0003) and IBD (IRR = 10.5; 95% CI = 2.20‐50.90; P = 0.003). The continuous net reclassification index was 0.63 for CRP, IL‐6, C‐peptide, and non‐HMW adiponectin and 0.46 for GLDH, indicating good predictive ability of these biomarkers. Conclusion: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors. (Hepatology 2014;60:858–871)