Occupational variation in the risk of female breast cancer in the Nordic countries

Objective

This study aimed to determine occupational variations in the incidence of breast cancer in the population-based cohort of Nordic Occupational Cancer Study (NOCCA).

Methods

The study included long-term follow-up data from almost 7.5 million Nordic women. Participants were assigned to one of the 54 occupational categories based on census records at the ages of 30–64 years. Sixty-two thousand cases of breast cancer were identified through record linkages between nationwide cancer registries in Finland, Sweden, Norway, Denmark, and Iceland, followed up between 1961 and 2005. Country-specific standardized incidence ratios (SIRs) with 95% confidence intervals were estimated.

Results

Overall, the highest risk elevations were seen among military personnel (SIR 1.58, 95% CI 1.03–2.32), dentists (SIR 1.43, 95% CI 1.31–1.56), and physicians (SIR 1.35, 95% CI 1.26–1.46). The lowest risks were observed among gardeners (SIR 0.76, 95% CI 0.74–0.78), farmers (SIR 0.80, 95% CI 0.78–0.82), and woodworkers (SIR 0.75, 95% CI 0.70–0.81). Welders, tobacco workers, and painters had higher SIRs for breast cancer diagnosed at age?<?50. A reduced risk was observed among forestry workers, welders, and fishery workers for breast cancers diagnosed both before and after age 50. The SIRs for breast cancer did not vary substantially by histology. A significantly increased risk of breast cancer was observed among laboratory workers in the latest calendar period (1991–2005) compared with earlier periods (1976–1990 and 1961–1975). Occupations such as farming, forestry, driving, and gardening had low SIRs during all periods.

Conclusions

The study suggests that the risk of breast cancer varies by occupation. Heterogeneity is also observed in some occupational categories according to age (before or after 50), histology, and calendar period.

     

Breast cancer risk factors and age at diagnosis: an Icelandic cohort study

An increasing number of studies indicates that the strength and even direction of association between breast cancer and established risk factors differ according to the woman's age when she develops the disease. This was studied in the setting of a population based cancer registry using a databank with information on age at menarche, parity, age at first birth, oral contraceptive (OC) use, lactation, height and weight. From a cohort of 80.219 women attending population-based cervical and breast cancer screening in Iceland, 1120 cases were identified, aged 26-90 years at diagnosis and 10,537 controls, individually matched to the cases on birth year and age when attending. Information given at last visit before diagnosis was used in the analysis, applying conditional logistic regression. Odds ratios and statistical strength of relationships varied according to age at diagnosis for age at first birth, number of births, duration of lactation, height and weight. The decreased risk associated with young age at first birth and increasing duration of breast feeding became less pronounced with advancing age at diagnosis. A reduced risk associated with an increasing number of births was not detected in women diagnosed under the age of 40. An increased risk associated with giving first birth after 30 years of age was mainly detected in women who had only given 1 birth and were diagnosed under the age of 40 (OR = 7.06 95% CI = 2.16-23.01). A positive association with height and especially with weight was confined to women diagnosed after the age of 55. The results confirm that age at diagnosis should be taken into account when studying the effects of breast cancer risk factors.     

Virtual screening for novel openers of pancreatic K(ATP) channels

Ligand-based virtual screening approaches were applied to search for new chemotype KCOs activating Kir6.2/SUR1 KATP channels. A total of 65 208 commercially available compounds, extracted from the ZINC archive, served as database for screening. In a first step, pharmacokinetic filtering via VolSurf reduced the initial database to 1913 compounds. Afterward, six molecules were selected as templates for similarity searches: similarity scores, obtained toward these templates, were calculated with the GRIND, FLAP, and TOPP approaches, which differently encode structural information into potential pharmacophores. In this way, we obtained 32 hit candidates, 16 via GRIND and eight each via FLAP and TOPP. For biological testing of the hit candidates, their effects on membrane potentials in HEK 293 cells expressing Kir6.2/SUR1 were studied. GRIND, FLAP, and TOPP all yielded hits, but no method top-ranked all the actives. Thus, parallel application of different approaches probably improves hit detection.     

Caffeine inhibits gene-specific repair of UV-induced DNA damage in hamster cells and in human xeroderma pigmentosum group C cells

We have studied the effect of caffeine on gene- and strandspecificDNA repair after exposure of Chinese hamster ovary cells andhuman xeroderma pigmentosum complementation group C (XPC) cellsto ultraviolet irradiation (UV). In hamster cells, caffeineinhibited the repair of cyclobutane dimers (CPDs) in the dihydrofolatereductase (DHFR) gene by up to 66% after 8 h of repair incubation.This effect was dose-dependent, with more inhibition at 10 thanat 1.5 mM caffeine. The inhibition was due to decreased repairin the transcribed strand of the hamster DHFR gene. This decreasein repair of CPDs in the DHFR gene correlated with an enhancementof UV-induced cell killing by caffeine. DNA repair was alsomeasured in the overall genome by repair—replication analysis.In hamster cells, caffeine caused a modest enhancement of repair.caffeine did not produce a significant effect on cell cycleprogression up to 8 h after UV irradiation, but it caused adistinct block in early S phase during the 24 h post-irradiationperiod. In XPC cells, 10 mM caffeine inhibited the removal ofCPDs from the transcribed strand of the DHFR gene by 92% Theremoval of all Photoproducts from the overall genome was inhibitedby 26% in these cells. Since the residual repair in XPC cellsis thought to occur in active genomic regions, we propose thatcaffeine preferentially inhibits gene-specific repair.     

Occupational exposure to wood dust and risk of nasal and nasopharyngeal cancer: A case‐control study among men in four nordic countries—With an emphasis on nasal adenocarcinoma

The current study aims to provide stronger evidence to aid in our understanding of the role of cumulative occupational exposure to (softwood‐dominated) mixed wood dust in aetiology of nasal cancer. We included broad exposure occurred in a range of wood‐processing occupation across varied industries in four Nordic countries. A population‐based case‐control study was conducted on all male cases with nasal adenocarcinoma (393 cases), other types of nasal cancer (2,446) and nasopharyngeal cancer (1,747) diagnosed in Finland, Sweden, Norway and Iceland between 1961 and 2005. For each case, five male controls, who were alive at the time of diagnosis of the case (index date), were randomly selected, matched by birth‐year and country. Cumulative exposures (CE)s to wood dust and formaldehyde before the index date were quantified based on a job‐exposure matrix linked to occupational titles derived from population censuses. Hazard ratios (HRs) for the CE of wood dust were estimated by conditional logistic regression, adjusted for CE to formaldehyde and 95% confidence intervals (CIs) were calculated. There was an increasing risk of nasal adenocarcinoma related to wood dust exposure. The HR in the highest CE category of wood dust (≥ 28.82 mg/m³‐years) was 16.5 (95% CI 5.05–54.1). Neither nonadenocarcinoma of the nose nor nasopharyngeal cancer could be linked to wood dust exposure. CE to softwood‐dominated mixed wood dusts is strongly linked with elevated risk in nasal adenocarcinoma but not with other types of nasal or nasopharyngeal cancer.     

Short stature and overweight in infants of Western Massachusetts

A cross‐sectional study of the nutritional status of 268 urban white, black and Puerto Rican infants, age 1–26 weeks, of three economic levels, was undertaken between November 1972 and March 1974. Subjects were selected at random. Mothers were interviewed and infants measured and weighed by a nutritionist during a single home visit. Crown‐heel length, weight and weight/height ratio of 254 full‐term infants are discussed. Physical characteristics of the children suggest that their diet was limited more in quality than in quantity. Limitations in linear growth and excessive weight gain were particularly noted in many boys under three months of age of all ethnic and socioeconomic groups, when compared to percentile distributions of the Child Research Council. Girls were generally less heavy for their length than boys, but girls from low income families tended to be heavier for their length than those from middle and high income families. Low income black children were longer than low income white and Puerto Rican children at the age of six months.     

Breast cancer risk associated with AURKA 91T -->A polymorphism in relation to BRCA mutations

In this study 759 breast cancer patients, including 9 BRCA1 and 98 BRCA2 mutation carriers, and 653 mutation-negative unaffected controls were genotyped for the AURKA 91T → A polymorphism. Individuals homozygous for the 91A allele were found to be at increased risk of breast cancer compared to 91T homozygotes (OR = 1.87; 95% CI = 1.09–3.21). This association was strengthened when cases carrying BRCA mutations were excluded (OR = 2.00; 95% CI = 1.15–3.47). BRCA carrier cases differed from sporadic cases and their allele distribution was very similar to controls. These results show a statistically significant increased risk of sporadic breast cancer for individuals that are homozygous for the 91A allele but no effect in carriers of BRCA mutations. This may throw light on previously conflicting results.