Andreas Pettersson

Mammographic Density Phenotypes and Risk of Breast Cancer: A Meta-analysis

BACKGROUND Fibroglandular breast tissue appears dense on mammogram, whereas fat appears nondense. It is unclear whether absolute or percentage dense area more strongly predicts breast cancer risk and whether absolute nondense area is independently associated with risk. METHODS We conducted a meta-analysis of 13 case-control studies providing results from logistic regressions for associations between one standard deviation (SD) increments in mammographic density phenotypes and breast cancer risk. We used random-effects models to calculate pooled odds ratios and 95% confidence intervals (CIs). All tests were two-sided with P less than .05 considered to be statistically significant. RESULTS Among premenopausal women (n = 1776 case patients; n = 2834 control subjects), summary odds ratios were 1.37 (95% CI = 1.29 to 1.47) for absolute dense area, 0.78 (95% CI = 0.71 to 0.86) for absolute nondense area, and 1.52 (95% CI = 1.39 to 1.66) for percentage dense area when pooling estimates adjusted for age, body mass index, and parity. Corresponding odds ratios among postmenopausal women (n = 6643 case patients; n = 11187 control subjects) were 1.38 (95% CI = 1.31 to 1.44), 0.79 (95% CI = 0.73 to 0.85), and 1.53 (95% CI = 1.44 to 1.64). After additional adjustment for absolute dense area, associations between absolute nondense area and breast cancer became attenuated or null in several studies and summary odds ratios became 0.82 (95% CI = 0.71 to 0.94; P heterogeneity = .02) for premenopausal and 0.85 (95% CI = 0.75 to 0.96; P heterogeneity < .01) for postmenopausal women. CONCLUSIONS The results suggest that percentage dense area is a stronger breast cancer risk factor than absolute dense area. Absolute nondense area was inversely associated with breast cancer risk, but it is unclear whether the association is independent of absolute dense area.

Women smoking and testicular cancer: one epidemic causing another?

In many countries the incidence of testicular cancer has increased epidemically, but the aetiology remains obscure. Maternal smoking during pregnancy has been suggested to be a cause, but a satisfactorily valid assessment of the hypothesis is still lacking. To evaluate the epidemiological relevance, we assessed the ecological correlation between female smoking habits and testicular cancer incidence in the Nordic countries. Data on smoking prevalence among women in 5‐year birth cohorts 1910–1940, at 25–29 years of age, were obtained through past studies of smoking habits in Sweden, Denmark, Norway and Finland. Testicular cancer incidence in the presumed offspring birth cohorts 1938–1968, was calculated using data from the respective cancer registries. For comparison, a similar analysis of male smoking and testicular cancer in the presumed offspring cohorts was carried out. The Pearson correlation coefficient between female smoking prevalence and testicular cancer incidence in the generation of the presumed offspring was 0.9 (p < 0.0001) for all countries combined. With the exception of Finland, the country‐specific correlations were of the same magnitude. In multivariate analysis, there was no correlation with male smoking. The strong geographical and temporal correlations between female smoking and testicular cancer indicate that if smoking during pregnancy is a cause of testicular cancer in the offspring, part of the increasing trends could be explained, and more importantly: avoided, by primary prevention.

Risk of contralateral testicular cancer among men with unilaterally undescended testis: A meta analysis

The association between undescended testis (cryptorchidism) and testicular cancer is established, but it is not known whether the risk of testicular cancer among men with unilateral maldescent is increased in both testes, or only on the undescended side. This is a meta‐analysis of 11 case‐control studies and 1 cohort study that all assessed the risk of testicular cancer separately for the undescended and descended testis. We used fixed‐effects meta‐analysis to calculate pooled estimates and 95% confidence intervals (CIs) for the relative risk. Of 199 tumors in men with unilateral cryptorchidism, 158 (79%) were on the ipsilateral side and 41 (21%) on the contralateral side. The pooled relative risks for testicular cancer in the ipsilateral and contralateral testis were 6.33 (95% CI, 4.30 to 9.31) and 1.74 (95% CI, 1.01 to 2.98), respectively. We conclude that in 1‐sided undescended testis, the risk of testicular cancer may be increased in both testes, although to a much greater extent on the ipsilateral side.

Accuracy of CAD/CAM-guided surgical template implant surgery on human cadavers: Part I

STATEMENT OF PROBLEM An optimal method for approaching the clinical surgical situation, when using preoperatively, virtually planned implant positioning, is to transfer data to a CAD/CAM-guided surgical template with the definitive position of the implant placed after surgery. The accuracy of CAD/CAM-guided surgeries must be determined to provide safe treatment. PURPOSE The purpose of this study was to compare the deviation between the position of virtually planned implants and the position of implants placed with a CAD/CAM-guided surgical template in the mandible and the maxilla in human cadavers. MATERIAL AND METHODS Ten maxillae and 7 mandibles, from completely edentulous cadavers, were scanned with CT, and 145 implants (Brånemark RP Groovy) were planned with software and placed with the aid of a CAD/CAM-guided surgical template. The preoperative CT scan was matched with the postoperative CT scan using voxel-based registration. The positions of the virtually planned implants were compared with the actual positions of the implants. Data were analyzed with a t test (alpha=.05). RESULTS The mean measurement differences between the computer-planned implants and implants placed after surgery for all implants placed were 1.25 mm (95% CI: 1.13-1.36) for the apex, 1.06 mm (95% CI: 0.97-1.16) for the hex, 0.28 mm (95% CI: 0.18-0.38) for the depth deviation, 2.64 degrees (95% CI: 2.41-2.87) for the angular deviation, and 0.71 mm (95% CI: 0.61-0.81 mm) for the translation deviation. CONCLUSIONS The results demonstrated a statistically significant difference between mandibles and maxillae for the hex, apex, and depth measurements in the variation between the virtually planned implant positions and the positions of the implants placed after surgery with a CAD/CAM-guided surgical template.

Milk and Dairy Consumption among Men with Prostate Cancer and Risk of Metastases and Prostate Cancer Death

Background: Whether milk and dairy intake after a prostate cancer diagnosis is associated with a poorer prognosis is unknown. We investigated postdiagnostic milk and dairy intake in relation to risk of lethal prostate cancer (metastases and prostate cancer death) among participants in the Health Professionals Follow-Up Study. Methods: The cohort consisted of 3,918 men diagnosed with apparently localized prostate cancer between 1986 and 2006, and followed to 2008. Data on milk and dairy intake were available from repeated questionnaires. We used Cox proportional hazards models to calculate HRs and 95% CIs of the association between postdiagnostic milk and dairy intake and prostate cancer outcomes. Results: We ascertained 229 prostate cancer deaths and an additional 69 metastases during follow-up. In multivariate analysis, total milk and dairy intakes after diagnosis were not associated with a greater risk of lethal prostate cancer. Men with the highest versus lowest intake of whole milk were at an increased risk of progression (HR = 2.15, 95% CI: 1.28–3.60; Ptrend < 0.01). Men in the highest versus lowest quintile of low-fat dairy intake were at a decreased risk of progression (HR = 0.62; 95% CI: 0.40–0.95; Ptrend = 0.07). Conclusions: With the exception of whole milk, our results suggest that milk and dairy intake after a prostate cancer diagnosis is not associated with an increased risk of lethal prostate cancer. Impact: This is the first larger prospective study investigating the relation between postdiagnostic milk and dairy intake and risk of lethal prostate cancer. Cancer Epidemiol Biomarkers Prev; 21(3); 428–36. ©2012 AACR.

Maternal smoking and the epidemic of testicular cancer--a nested case-control study.

For no apparent reason, the incidence of testicular cancer has increased to epidemic proportions in many countries. Pregnancy smoking has been suggested to be a cause. Previous analytical studies have been negative, but the inherent difficulties in retrospective assessment of this exposure have led to no definite conclusion. We have conducted a population‐based case–control study on 192 cases of testicular germ‐cell cancer—born in Sweden in 1973 onwards and aged ≥15 at cancer diagnosis—and 494 matched controls, where data on maternal smoking were collected during pregnancy. We found no association with testicular cancer for maternal smoking during pregnancy (OR, 0.91; 95% CI, 0.64–1.30), and there was no evidence of a dose–response effect. We conclude that the epidemic rise in testicular cancer in many populations is not due to the surge in smoking among women.

Global DNA hypomethylation in prostate cancer development and progression: a systematic review

Background:The role of global DNA methylation in prostate cancer (PCa) remains largely unknown. Our aim was to summarize evidence on the role of global DNA hypomethylation in PCa development and progression.Methods:We searched PubMed through December 2013 for all studies containing information on global methylation levels in PCa tissue and at least one non-tumor comparison tissue and/or studies reporting association between global methylation levels in PCa tissue and survival, disease recurrence or at least one clinicopathological prognostic factor. We summarized results using non-parametric comparisons and P-value summary methods.Results:We included 15 studies in the review: 6 studies with both diagnostic and prognostic information, 5 studies with only diagnostic information and 4 studies with only prognostic information. Quantitative meta-analysis was not possible because of the large heterogeneity in molecular techniques, types of tissues analyzed, aims and study designs. Summary statistical tests showed association of DNA hypomethylation with PCa diagnosis (P<0.006) and prognosis (P<0.001). Restriction to studies assessing 5-methylcytosine or long interspersed nucleotide element-1 revealed results in the same direction. Analyses restricted to specific clinicopathological features showed association with the presence of metastasis and tumor stage in all tests with P<0.03, and no association with Gleason score (all tests P>0.1 except for the weighted Z-test, P=0.05).Conclusion:DNA hypomethylation was associated with PCa development and progression. However, due to the heterogeneity and small sample sizes of the included studies, along with the possibility of publication bias, this association requires additional assessment.

Dietary lycopene intake and risk of prostate cancer defined by ERG protein expression

BACKGROUND There is limited evidence that supports etiologically distinct molecular subtypes of prostate cancer, the identification of which may improve prevention. Given their antioxidant properties, we hypothesized that lycopene and tomato sauce may be especially protective against diseases harboring the common gene fusion transmembrane protease, serine 2 (TMPRSS2):v-ets avian erythroblastosis virus E26 oncogene homolog (ERG). OBJECTIVE We aimed to examine associations between estimated lycopene and tomato sauce intake and the risk of prostate cancer defined by ERG protein expression subtype. DESIGN Our study population consisted of a prospective cohort of 46,719 men from the Health Professionals Follow-Up Study. TMPRSS2:ERG was assessed by ERG immunohistochemistry on tumor tissue microarrays constructed from radical prostatectomy specimens. We used multivariable competing risk models to calculate HRs and 95% CIs for the risk of ERG-positive and, separately, ERG-negative disease. We implemented inverse probability weighting to account for evaluating ERG status only in surgically treated cases. RESULTS During 23 y of follow-up, 5543 men were diagnosed with prostate cancer, among whom 884 were assayed for ERG (426 ERG-positive). With inclusion of only the latter cases, increasing cumulative average tomato sauce intake was associated with a decreased risk of prostate cancer overall (≥2 servings/wk compared with <1 serving/mo; multivariable HR: 0.70; 95% CI: 0.52, 0.95; P-trend = 0.002). With respect to molecular subtypes, cumulative average tomato sauce intake was associated with a decreased risk of ERG-positive disease (HR: 0.54; 95% CI: 0.37, 0.81; P-trend = 0.004) but not with ERG-negative disease (HR: 0.96; 95% CI: 0.62, 1.50; P-trend = 0.10) (P-heterogeneity = 0.04). Increasing quintiles of lycopene intake were associated with a decreased risk of both subtypes (P-heterogeneity = 0.79). Inverse probability weighting did not materially change the results. CONCLUSIONS Our results lend some support to the hypothesis that prostate cancers that harbor TMPRSS2:ERG may be etiologically distinct from fusion-negative cancers. In particular, tomato sauce consumption may play a role in reducing TMPRSS2:ERG-positive disease.

Perinatal risk factors for childhood testicular germ-cell cancer: A Nordic population-based study

INTRODUCTION In contrast to research in adults, there have been limited studies on testicular germ-cell cancer among boys aged <15 years. The aim of the study was to investigate the association between perinatal characteristics and childhood testicular germ-cell cancer. METHODS We identified 152 patients with childhood germ-cell cancer among boys (<15 years) born in Norway, Sweden, Finland and Denmark between 1967 and 2006 using the cancer and medical birth registries. For each case we sampled 10 population controls matched on year and country of birth. We used conditional logistic regression analysis to estimate odds ratios for cancer risk. RESULTS There was a weak, positive association between high (≥4000 g) birth weight and childhood testicular germ-cell cancer (adjusted OR=1.25; 95% CI: 0.83-1.90) compared with normal birth weight, and a correspondingly elevated risk for low birth weight (adjusted OR=1.41; 95% CI: 0.43-4.56). For Ponderal Index (PI) there was an increased risk for low and high values compared to those in the middle category (adjusted OR=1.64; 95% CI: 1.03-2.62 and 1.67; 95% CI: 0.93-2.99), respectively. There was no association between birth length and childhood testicular germ-cell cancer. The adjusted OR for testicular cancer among first born was 1.40; 95% CI: 0.96-2.05. Greater maternal age and less maternal education appeared to increase the risk, but the estimates were not statistically significant. CONCLUSION We found a U-shaped association between fetal growth, measured as the PI, and childhood testicular germ-cell cancer. Our findings support the notion that abnormal fetal growth rate confers a risk in pediatric testicular cancer [corrected].

Global Hypomethylation (LINE-1) and Gene-Specific Hypermethylation (GSTP1) on Initial Negative Prostate Biopsy as Markers of Prostate Cancer on a Rebiopsy

Purpose: Men at risk of missed prostate cancer on a negative biopsy often undergo a rebiopsy. We evaluated whether global hypomethylation, measured through LINE-1 methylation, and GSTP1 hypermethylation on a negative biopsy are associated with subsequent prostate cancer diagnosis. Experimental Design: We performed a case–control study nested in an unselected series of 737 men who received at least two prostate biopsies at least three months apart at the Molinette Hospital (Turin, Italy). Two pathology wards were included for replication purposes. The study included 67 cases and 62 controls in Ward 1 and 62 cases and 66 controls in Ward 2. We used pyrosequencing to analyze LINE-1 and GSTP1 methylation in the negative biopsies. Odds ratios (OR) of prostate cancer diagnosis were estimated using conditional logistic regression. Results: After mutual adjustment, GSTP1 hypermethylation was associated with an OR of prostate cancer diagnosis of 5.1 (95% confidence interval: 1.7–14.9) in Ward 1 and 2.0 (0.8–5.3) in Ward 2, whereas an association was suggested only for low LINE-1 methylation levels (<70% vs. 70%–74%) with an OR of 2.1 (0.5–9.1) in Ward 1 and 1.6 (0.4–6.1) in Ward 2. When the two wards were combined the association was stronger for tumors with Gleason score ≥4+3 [GSTP1 hypermethylation: 9.2 (2.0–43.1); LINE-1 (<70% vs. 70%–74%): 9.2 (1.4–59.3)]. GSTP-1 alone improved the predictive capability of the model (P = 0.007). Conclusions: GSTP1 hypermethylation on a negative biopsy is associated with the risk of prostate cancer on a rebiopsy, especially of high-grade prostate cancer. Consistent results were found only for extremely low LINE-1 methylation levels. Clin Cancer Res; 22(4); 984–92. ©2015 AACR.