Second primary malignancies in patients with male breast cancer

An international multicentre study of first and second primary neoplasms associated with male breast cancer was carried out by pooling data from 13 cancer registries. Among a total of 3409 men with primary breast cancer, 426 (12.5%) developed a second neoplasia; other than breast cancer, a 34% overall excess risk of second primary neoplasia, affecting the small intestine (standardised incidence ratio, 4.95, 95% confidence interval, 1.35–12.7), rectum (1.78, 1.20–2.54), pancreas (1.93, 1.14–3.05), skin (nonmelanoma, 1.65, 1.16–2.29), prostate (1.61, 1.34–1.93) and lymphohaematopoietic system (1.63, 1.12–2.29). A total of 225 male breast cancers was recorded after cancers other than breast cancer, but an increase was found only after lymphohaematopoietic neoplasms. BRCA2 (and to some extent BRCA1) mutations may explain the findings for pancreatic and prostate cancers. Increases at other sites may be related to unknown factors or to chance. This large study shows that the risks for second discordant tumours after male breast cancer pose only a moderate excess risk

Risks of second primary cancer among patients with major histological types of lung cancers in both men and women

10.1038/sj.bjc.6605616British Journal of Cancer10271190-1195BJCA

Second primary cancers among 109 000 cases of non-Hodgkin's lymphoma

An analysis of other primary cancers in individuals with non-Hodgkin's lymphoma (NHL) can help to elucidate this cancer aetiology. In all, 109 451 first primary NHL were included in a pooled analysis of 13 cancer registries. The observed numbers of second cancers were compared to the expected numbers derived from the age-, sex-, calendar period- and registry-specific incidence rates. We also calculated the standardised incidence ratios for NHL as a second primary after other cancers. There was a 47% (95% confidence interval 43–51%) overall increase in the risk of a primary cancer after NHL. A strongly significant (P<0.001) increase was observed for cancers of the lip, tongue, oropharynx*, stomach, small intestine, colon*, liver, nasal cavity*, lung, soft tissues*, skin melanoma*, nonmelanoma skin*, bladder*, kidney*, thyroid*, Hodgkin's lymphoma*, lymphoid leukaemia* and myeloid leukaemia. Non-Hodgkin's lymphoma as a second primary was increased after cancers marked with an asterisk. Patterns of risk indicate a treatment effect for lung, bladder, stomach, Hodgkin's lymphoma and myeloid leukaemia. Common risk factors may be involved for cancers of the lung, bladder, nasal cavity and for soft tissues, such as pesticides. Bidirectional effects for several cancer sites of potential viral origin argue strongly for a role for immune suppression in NHL

Pathway Analysis of Renal Cell Carcinoma Genome-Wide Association Studies Identifies Novel Associations.

Background Much of the heritable risk of renal cell carcinoma (RCC) associated with common genetic variation is unexplained. New analytic approaches have been developed to increase the discovery of risk variants in genome-wide association studies (GWAS), including multi-locus testing through pathway analysis.Methods We conducted a pathway analysis using GWAS summary data from six previous scans (10,784 cases and 20,406 controls) and evaluated 3,678 pathways and gene sets drawn from the Molecular Signatures Database. To replicate findings, we analyzed GWAS summary data from the UK Biobank (903 cases and 451,361 controls) and the Genetic Epidemiology Research on Adult Health and Aging cohort (317 cases and 50,511 controls).Results We identified 14 pathways/gene sets associated with RCC in both the discovery (P -5, the Bonferroni correction threshold) and replication (P P -5 in discovery and replication sets combined) were observed for CASP9, TIPIN, and CDKN2C. The strongest SNP signal was for rs12124078 (P Discovery = 2.6 × 10-5; P Replication = 1.5 × 10-4; P Combined = 6.9 × 10-8), a CASP9 expression quantitative trait locus.Conclusions Our pathway analysis implicates genetic variation within the PI3K/AKT pathway as a source of RCC heritability and identifies several promising novel susceptibility genes, including CASP9, which warrant further investigation.Impact Our findings illustrate the value of pathway analysis as a complementary approach to analyzing GWAS data

Alcohol and mortality in Russia: prospective observational study of 151,000 adults.

BACKGROUND: Russian adults have extraordinarily high rates of premature death. Retrospective enquiries to the families of about 50,000 deceased Russians had found excess vodka use among those dying from external causes (accident, suicide, violence) and eight particular disease groupings. We now seek prospective evidence of these associations. METHODS: In three Russian cities (Barnaul, Byisk, and Tomsk), we interviewed 200,000 adults during 1999-2008 (with 12,000 re-interviewed some years later) and followed them until 2010 for cause-specific mortality. In 151,000 with no previous disease and some follow-up at ages 35-74 years, Poisson regression (adjusted for age at risk, amount smoked, education, and city) was used to calculate the relative risks associating vodka consumption with mortality. We have combined these relative risks with age-specific death rates to get 20-year absolute risks. FINDINGS: Among 57,361 male smokers with no previous disease, the estimated 20-year risks of death at ages 35-54 years were 16% (95% CI 15-17) for those who reported consuming less than a bottle of vodka per week at baseline, 20% (18-22) for those consuming 1-2·9 bottles per week, and 35% (31-39) for those consuming three or more bottles per week; trend p&lt;0·0001. The corresponding risks of death at ages 55-74 years were 50% (48-52) for those who reported consuming less than a bottle of vodka per week at baseline, 54% (51-57) for those consuming 1-2·9 bottles per week, and 64% (59-69) for those consuming three or more bottles per week; trend p&lt;0·0001. In both age ranges most of the excess mortality in heavier drinkers was from external causes or the eight disease groupings strongly associated with alcohol in the retrospective enquiries. Self-reported drinking fluctuated; of the men who reported drinking three or more bottles of vodka per week who were reinterviewed a few years later, about half (185 of 321) then reported drinking less than one bottle per week. Such fluctuations must have substantially attenuated the apparent hazards of heavy drinking in this study, yet self-reported vodka use at baseline still strongly predicted risk. Among male non-smokers and among females, self-reported heavy drinking was uncommon, but seemed to involve similar absolute excess risks. INTERPRETATION: This large prospective study strongly reinforces other evidence that vodka is a major cause of the high risk of premature death in Russian adults. FUNDING: UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Union, WHO International Agency for Research on Cancer

Risk of second malignant neoplasms after childhood central nervous system malignant tumours: An international study

10.1016/j.ejca.2008.02.012European Journal of Cancer446830-839EJCA

Second primary malignancies among women with uterine sarcoma

10.1016/j.ygyno.2012.04.002Gynecologic Oncology126130-35GYNO