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The association of breast cancer with passive and active smoking was investigated in slow and fast acetylators of aromatic amines in a Geneva, Switzerland, study in 1996–1997. A slow acetylator was homozygous for one, or heterozygous for two, of three N-acetyltransferase 2 (NAT2) polymorphisms determined on buccal cell DNA from 177 breast cancer cases and 170 age-matched, population controls. The reference group consisted of women never regularly exposed to active or passive smoke. Among premenopausal women, the odds ratios were homogeneous in slow and fast acetylators: 3.2 (95% confidence interval (CI): 1.2, 8.7) for passive smoking and 2.9 (95% CI: 1.1, 7.5) for active smoking. Among postmenopausal women, the odds ratios for fast acetylators were 11.6 (95% CI: 2.2, 62.2) for passive and 8.2 (95% CI: 1.4, 46.0) for active smoking; the corresponding effects were also apparent but less strong in slow acetylators. After the nonexposed and the passive smokers were grouped in a single reference category, active smoking was associated with postmenopausal breast cancer in slow acetylators (odds ratio (OR) = 2.5, 95% CI: 1.0, 6.2) but not in fast acetylators (OR = 1.3, 95% CI: 0.5, 3.3). Thus, the associations of both passive and active smoking with breast cancer appear stronger in fast than in slow NAT2 genotypes. Separating passive smokers from the nonexposed impacts on the inference about a possible NAT2-smoking interaction. Am J Epidemiol 2000;152:226–32. [ABSTRACT FROM PUBLISHER]

This study evaluates the risk of acute myeloid leukaemia (AML) in patients treated for breast cancer. We included all 6360 breast cancer patients that were recorded at the Geneva Cancer Registry between 1970 and 1999. Patients were followed for AML occurrence until December 2000. We calculated standardized incidence ratios of AML and identified factors modifying the risk of AML by multivariate Cox analysis. Twelve (0.2%) patients developed AML. In general, patients treated for breast cancer had a 3.5-fold (95% confidence interval (CI): 1.8-6.0) increased risk of developing AML compared with the general population. In particular, patients who were older than 70 years at breast cancer diagnosis and those treated with radiotherapy (with or without chemotherapy) had a significantly increased risk of developing AML. This population-based study confirms that radiotherapy increases the risk of AML. Due to the relatively low number of women treated with chemotherapy without radiotherapy and due to the infrequency of the disease, the question of whether chemotherapy alone increases this risk of AML cannot yet be answered.

The effect of age on breast cancer survival is still a matter of controversy. Breast cancer in young women is thought to be more aggressive and to have worse prognosis but results from clinical research have been neither consistent nor definitive. In this study, we have assessed the impact of young age at diagnosis on tumor characteristics, treatment and survival of breast cancer. The study included 82 very young (< or = 35 years), 790 young (36-49), and 2125 older (50-69) women recorded between 1990 and 2001 at the Geneva Cancer Registry. Very young and young patients had more often stage II cancers (P = 0.009), poorly differentiated (P < 0.001) and estrogen receptor negative (P < 0.001) tumors. They were also more likely to receive chemotherapy (P < 0.001) and less likely to receive hormonal therapy (P < 0.001). Specific five-year survival was not different in the three groups (91%, 90%, and 89% for very young, young and older, respectively). When adjusting for all prognostic variables, age was not significantly related to mortality from breast cancer with a hazard ratio of 0.8 (95% CI: 0.3-2.0) for very young and 1.1 (95% CI: 0.8-1.4) for young patients compared to older women. Tumor stage, differentiation, estrogen receptor status, surgery, and radiotherapy were all independent determinants of breast cancer prognosis. We conclude that age is not an independent prognostic factor when accounting for breast tumor characteristics and treatment.

Parasite-mediated sexual selection theory presumes that variation in sexual traits reliably reflects variation in parasite resistance among available mates. One mechanism that may warrant signal honesty involves costs of immune system activation in the case of a parasitic infection. We investigated this hypothesis in male field crickets Gryllus campestris, whose attractiveness to females depends on characteristics of the sound-producing harp that are essentially fixed following adult eclosion. During the nymphal stage, males subjected to one of two feeding regimes were challenged with bacterial lipopolysaccharides (LPS) to investigate condition-dependent effects on harp development as compared to other adult traits. Nymphal nutritional status positively affected adult body size, condition, and harp size. However, nymphal immune status affected harp size only, with LPS-males having smaller harps than control-injected males. In addition, the harps of LPS-males showed a lesser degree of melanization, indicating an enhanced substrate use by the melanin-producing enzyme cascade of the immune system. Thus, past immune status is specifically mirrored in sexual traits, suggesting a key role for deployment costs of immunity in parasite-mediated sexual selection.

A recent paper from the United States reported a sharp and unexplained increase in invasive lobular breast cancer incidence since 1977 (Li et al., Cancer 2000;88:2561-9). We investigated if this trend was also present in Geneva, Switzerland, where breast cancer incidence is one of the highest in Europe. We analyzed trends in breast cancer incidence according to histologic subtype, age and stage, to clarify the pattern. Our population-based study includes all histologically confirmed invasive breast carcinomas (n = 6,247) recorded between 1976 and 1999 at the Geneva Cancer Registry. Breast histology was classified as ductal carcinoma, lobular carcinoma and other. Incidence trends were studied by log-linear regression analyses. Models including effects of age, period and birth cohorts were used to describe rising incidence trends. The incidence of ductal carcinoma increased 1.2% per year (p(trend) < 0.001) from 85.2 to 110.1/100,000. This increase concerned women aged 50-69 years and early-stage tumors. Lobular cancer incidence increased disproportionately (14.4% per year, p(trend) < 0.01) and rose from 2.9 to 20.5/100,000. This increase affected all age categories and both localized and advanced stages. In addition, a strong age-cohort effect was present (p < 0.05), and women aged 50-59 years born after 1944 experienced the most marked increase. Our study shows a disproportionate increase of lobular breast cancer incidence compared to ductal cancer incidence. Contrary to ductal cancer, trends for lobular cancer are unlikely to be explained by increased use of screening mammography. Other explanations must be researched, in particular the role played by hormone replacement therapy., (Copyright 2003 Wiley-Liss, Inc.)