Is Smoking an Independent Risk Factor for Invasive Cervical Cancer? A Nested Case-Control Study Within Nordic Biobanks

The strong correlation between smoking and exposure to oncogenichuman papillomaviruses (HPVs) has made it difficult to verifythe independent role of smoking in cervical carcinogenesis.Thus, the authors evaluated this role. Five large Nordic serumbanks containing samples from more than 1,000,000 subjects werelinked with nationwide cancer registries (1973–2003).Serum samples were retrieved from 588 women who developed invasivecervical cancer and 2,861 matched controls. The samples wereanalyzed for cotinine (a biomarker of tobacco exposure) andantibodies to HPV types 16 and 18, herpes simplex virus type2, and Chlamydia trachomatis. Smoking was associated with therisk of squamous cell carcinoma (SCC) among HPV16- and/or HPV18-seropositiveheavy smokers (odds ratio = 2.7, 95% confidence interval: 1.7,4.3). A similar risk of SCC (odds ratio = 3.2, 95% confidenceinterval: 2.6, 4.0) was found in heavy smokers after adjustmentfor HPV16/18 antibodies. The point estimates increased withincreasing age at diagnosis and increasing cotinine level. Thisstudy confirms that smoking is an independent risk factor forcervical cancer/SCC in women infected with oncogenic HPVs. Thesefindings emphasize the importance of cervical cancer preventionamong women exposed to tobacco smoke. carcinoma, squamous cell; risk factors; smoking; uterine cervical neoplasms     

Positive Association Between DNA Strand Breaks in Peripheral Blood Mononuclear Cells and Polyunsaturated Fatty Acids in Red Blood Cells From Women

Lipid peroxidation of polyunsaturated fatty acids (PUFA) generates reactive products that may cause DNA damage. To examine the possible relationship between DNA damage in peripheral blood mononuclear cells (PBMC) and the concentration of PUFA in red blood cells (RBC), endogenous DNA strand breaks, formamidopyrimidine DNA glycosylase (FPG) sites, and hydrogen peroxide (H₂O₂) sensitive sites were evaluated by the comet assay in blood samples from 98 Icelandic women. Fatty acid composition of RBC was analyzed by gas chromatography. Endogenous DNA strand breaks in PBMC correlated positively with the concentration of total PUFA, total n-3 PUFA, docosahexaenoic acid, linoleic acid, oleic acid, and palmitic acid in RBC. However, there was no association between FPG sites or H₂O₂ sensitive sites in DNA in PBMC and the concentration of total PUFA or total saturated fatty acid in RBC. As there was no association between oxidative DNA damage or sensitivity of DNA to oxidative stress and the concentration of PUFA in RBC, the positive association between endogenous DNA strand breaks in PBMC and the concentration of total PUFA in RBC is probably not related to oxidative stress.     

Assessing disease risk in genome-wide association studies using family history

We show how to use reports of cancer in family members to discover additional genetic associations or confirm previous findings in genome-wide association (GWA) studies conducted in case-control, cohort, or cross-sectional studies. Our novel family history-based approach allows economical association studies for multiple cancers, without genotyping of relatives (as required in family studies), follow-up of participants (as required in cohort studies), or oversampling of specific cancer cases (as required in case-control studies). We empirically evaluate the performance of the proposed family history-based approach in studying associations with prostate and ovarian cancers, using data from GWA studies previously conducted within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The family history-based method may be particularly useful for investigating genetic susceptibility to rare diseases for which accruing cases may be very difficult, by using disease information from nongenotyped relatives of participants in multiple case-control and cohort studies designed primarily for other purposes.     

A population-based familial aggregation analysis indicates genetic contribution in a majority of renal cell carcinomas

The etiology of RCC is incompletely understood and the inherited genetic contribution uncertain. Although there are rare mendelian forms of RCC stemming from inherited mutations, most cases are thought to be sporadic. We sought to determine the extent of familial aggregation among Icelandic RCC patients in general. Medical and pathologic records for all patients diagnosed with RCC in Iceland between 1955 and 1999 were reviewed. This included a total of 1,078 RCC cases, 660 males and 418 females. With the use of an extensive computerized database containing genealogic information on 630,000 people in Iceland during the past 11 centuries, several analyses were conducted to determine whether the patients were more related to each other than members drawn at random from the population. Patients with RCC were significantly more related to each other than were subjects in matched groups of controls. This relatedness extended beyond the nuclear family. RRs were significantly greater than 1.0 for siblings, parents and cousins of probands. RRs were 2-3 for first-degree relatives and 1.6 for third-degree relatives. The risk of RCC is significantly higher for members of the extended family of an affected individual, as well as the nuclear family. Our results indicate that germline mutations are significantly involved in what has been defined as sporadic RCC.     

Interpreting trends in prostate cancer incidence and mortality in the five Nordic countries

Trends in incidence and mortality rates of prostate cancer were analyzed using data from the national cancer registries of Denmark, Finland, Iceland, Norway, and Sweden. Joinpoint regression models were used to quantify temporal trends for the period from 1980 to 2004. Incidence rates were increasing and similar in the Nordic countries during the 1980s. Around 1990, a more rapid incidence increase began in all Nordic countries except Denmark, where an increase was seen 5 years later. In 2001, incidence rates in Denmark were half of those seen in the other Nordic countries, but mortality rates varied only marginally among countries. Mean annual declines in prostate cancer mortality of 1.9% (95% CI = 0.4% to 3.3%) and 1.8% (95% CI = 0.5% to 3.0%) were observed from 1996 to 2004 in Finland and Norway, respectively. During the same period, mortality rates leveled off in Iceland and Sweden but continued to increase in Denmark. The rapid increase in incidence during the early 1990s coincided with the introduction of the prostate-specific antigen (PSA) test and conveys little information about the occurrence of potentially lethal disease. Mortality rates, however, have recently stabilized or declined in countries where PSA testing and curative treatment have been commonly practiced since the late 1980s. Although other explanatory factors may be in operation, these trends are consistent with a moderate effect of increased curative treatment of early diagnosed prostate cancer and improved treatment of more advanced disease.     

Familial risks in nervous system tumours: joint Nordic study

Background:

Familial nervous system cancers are rare and limited data on familial aspects are available particularly on site-specific tumours.

Methods:

Data from five Nordic countries were used to analyse familial risks of nervous system tumours. Standardised incidence ratios (SIRs) were calculated for offspring of affected relatives compared with offspring of non-affected relatives.

Results:

The total number of patients with nervous system tumour was 63 307, of whom 32 347 belonged to the offspring generation. Of 851 familial patients (2.6%) in the offspring generation, 42 (4.7%) belonged to the families of a parent and at least two siblings affected. The SIR of brain tumours was 1.7 in offspring of affected parents; it was 2.0 in siblings and 9.4 in families with a parent and sibling affected. For spinal tumours, the SIRs were much higher for offspring of early onset tumours, 14.0 for offspring of affected parents and 22.7 for siblings. The SIRs for peripheral nerve tumours were 16.3 in offspring of affected parents, 27.7 in siblings and 943.9 in multiplex families.

Conclusion:

The results of this population-based study on medically diagnosed tumours show site-, proband- and age-specific risks for familial tumours, with implications for clinical genetic counselling and identification of the underlying genes.     

Positive association between DNA strand breaks in peripheral blood mononuclear cells and polyunsaturated fatty acids in red blood cells from women

Lipid peroxidation of polyunsaturated fatty acids (PUFA) generates reactive products that may cause DNA damage. To examine the possible relationship between DNA damage in peripheral blood mononuclear cells (PBMC) and the concentration of PUFA in red blood cells (RBC), endogenous DNA strand breaks, formamidopyrimidine DNA glycosylase (FPG) sites, and hydrogen peroxide (H2O2) sensitive sites were evaluated by the comet assay in blood samples from 98 Icelandic women. Fatty acid composition of RBC was analyzed by gas chromatography. Endogenous DNA strand breaks in PBMC correlated positively with the concentration of total PUFA, total n-3 PUFA, docosahexaenoic acid, linoleic acid, oleic acid, and palmitic acid in RBC. However, there was no association between FPG sites or H(2)O(2) sensitive sites in DNA in PBMC and the concentration of total PUFA or total saturated fatty acid in RBC. As there was no association between oxidative DNA damage or sensitivity of DNA to oxidative stress and the concentration of PUFA in RBC, the positive association between endogenous DNA strand breaks in PBMC and the concentration of total PUFA in RBC is probably not related to oxidative stress.     

Increasing preoperative body size in breast cancer patients between 2002 and 2016: implications for prognosis

Overweight and obesity are increasing worldwide, but the extent in breast cancer patients is unknown. The two aims were to study secular trends in preoperative body mass index (BMI), waist circumference, and breast volume and their impacts on clinical outcome. BMI, waist circumference, and breast volume were measured preoperatively in 24–99-year-old primary breast cancer patients (n?=?640) in Sweden 2002–2016. The measurements were analyzed alone and combined in relation to recurrence and overall survival (OS). BMI, waist circumference, and breast volume increased 2002–2016 (p_trends?<?0.0001). Of these, a breast volume?≥?850 mL was associated with the strongest recurrence-risk (adjusted hazard ratio [_adjHR] 1.67; 95% CI 1.17–2.39), especially combined with waist circumference?≥?80 cm (_adjHR 2.07; 95% CI 1.25–3.44), while BMI?≥?25 kg/m² or large waist circumference conferred almost a twofold risk for death (both Log-Rank p?≤?0.0001). Chemotherapy seemed to counteract the negative impact of a high BMI or large waist circumference on OS. Large breast volume was the strongest predictor for recurrence in all treatment groups. In conclusion, preoperative BMI, waist circumference, and breast volume increased between 2002 and 2016. Larger body size negatively impacted breast cancer-free interval and OS. If confirmed, body measurements may help select patients requiring more individualized treatment.     

Cancer prevalence in Northern Europe: the EUROPREVAL study.

BACKGROUND: Information on cancer prevalence is of importance for health planning and resource allocation, but is not always available. In order to obtain such data in a comparable way a systematic evaluation of cancer prevalence in Europe was undertaken within the EUROPREVAL project. PATIENTS AND METHODS: Standardised data were collected from 38 population-based registries on almost 3 million cancer patients diagnosed between 1970 and 1992. The prevalence of 11 specific cancer types was estimated at the index date of 31 December 1992. This study deals with the northern countries Denmark, Estonia, Finland, Iceland and Sweden. RESULTS: There were large differences between these countries, Sweden having the highest prevalence rate of 3050 per 100 000 and Estonia the lowest, 1339 per 100 000. This difference is mainly due to a high proportion of cancers with favourable prognosis such as breast cancer, prostate cancer and melanoma, better survival and longer life expectancy in Sweden, whereas Estonia has a higher proportion of stomach and lung cancer with poor prognosis, worse survival and much shorter life expectancy, especially for males. For most tumour types, the Nordic countries did better than Estonia. There are indications that cancer patients in Estonia, as well as in Denmark, have a more advanced stage at diagnosis and that the Estonian health-care system is less efficient. CONCLUSIONS: Despite many similarities and a common historical background, the northern countries in Europe that participated in the EUROPREVAL study display quite different cancer patterns and prevalence. Reasons for these variations are discussed.     

Testicular germ cell tumours in Iceland: a nationwide clinicopathological study

The purpose of this study was to examine the pathology of all germ cell tumours of the testis diagnosed in Iceland 1955-2002. A total of 214 patients were included in the study. The current age-standardized incidence was found to be 6.1 per 100,000 and had increased almost fourfold during the study period. Seminoma was diagnosed in 55% of cases. Non-seminomas were diagnosed in 45%, and these were further classified as mixed germ cell tumours (33%), embryonal carcinoma (8%), teratoma (3%), and yolk sac tumour (n=1). The mean age at diagnosis was significantly higher for the seminomas than the non-seminomas (38 years versus 29 years) (p<0.001) and the non-seminomas were diagnosed at a significantly higher stage than the seminomas (p<0.001). Thus, in seminoma patients the tumour was localized to the testis (stage I) in 81% of cases, in 17% of patients the tumour had spread to the lymph nodes (stage II or III), and only 2% had extranodal metastasis at diagnosis (stage IV). In contrast, in the non-seminoma patients, the tumours were found to be stage I in 56%, stage II or III in 24%, and stage IV in 20% of cases. No significant difference in staging was found between non-seminoma subtypes. Identification of necrosis or vascular invasion was significantly associated with metastatic disease at diagnosis (p=0.002). During the study period a significant increase in stage I tumours was found as well as a decrease in the size of the tumours.