Cancer risks among long-standing spouses

We estimated risks for concordant and discordant cancers in spouses in order to quantify cancer risks from the shared environment. The study was restricted to spouses who had one or more children in common and who lived together for at least 15 years after the first child's birth. The nation-wide Family-Cancer Database was used as the source of family and cancer data. Standardised incidence ratios were calculated for concordant and discordant cancers in spouses after 50 years of age. Among the 18 cancer sites considered, only three sites, stomach, lung and bladder, showed concordant increases of cancer among spouses, standardised incidence ratios ranging only from 1.19 to 1.38. Additionally, gastric and pancreatic cancer were associated among spouses, as did many cancers which were related to tobacco smoking or human papilloma virus infection. By contrast, standardised incidence ratios of colon, rectal, renal and skin cancers showed no increases among spouses. Shared lifestyle among family members seems to explain only a small proportion of familial cancer susceptibility. Because lifestyles are likely to differ more between parents and offspring than between spouses, familial cancer risks between parents and offspring are even more likely to be due to heritable than environmental effects

Influence of family history on risk of second primary cancers and survival in patients with squamous cell skin cancer

Summary Background Patients with squamous cell skin cancer (SCC) have an excellent prognosis but second primary cancers (SPCs) weaken survival prospects. Family history is a known risk factor for cancer but whether it is a risk factor for SPC in patients with SCC is not known. Objectives To quantify the risk of family history on SPCs in patients with SCC and estimate survival probabilities of patients with SPCs depending on family history. Methods With 13 945 histologically verified SCCs, relative risks (RRs) were estimated for family history using a generalized regression model. For survival analysis, hazard ratios (HRs) were assessed using a multivariable Cox proportional-hazards model. Results Family history of invasive SCC increased risk of second invasive SCC [RR = 42·92, 95% confidence interval (CI) 33·69?50·32] compared with risk without family history (RR 19·12, 95% CI 17·88?21·08). Family history of any nonskin cancer in invasive SCC increased risk of the same cancers to be diagnosed as SPC (RRFH = 1·48, 95% CI 1·35?1·61 vs. RRno FH = 1·40, 95% CI 1·32?1·48); significant increases were observed for seven different nonskin cancers. Most results were replicated for in situ SCC. SPC was deleterious for survival irrespective of family history; HR for patients with SPC was 4·28 (95% CI 3·83?4·72) vs. those without SPC (1·04). Conclusions Family history of nonskin cancer was associated with approximately a doubling of risk for SPCs in patients with SCC. SPC increases the death rate in patients with SCC 3?4 times, irrespective of family history. Taking family history into account at SCC diagnosis may help prevention or early detection of SPCs. What's already known about this topic? Second primary cancers (SPCs) are frequently diagnosed in patients with invasive and in situ squamous cell carcinoma (SCC); some epidemiological studies suggest a link to immune dysfunction. Family history of cancer is a risk factor for practically all first primary cancers but whether it also influences risk of SPCs in patients with SCC is not known. The possible influence of family history on survival in patients with SCC remains to be established.Peer reviewe

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.British Journal of Cancer advance online publication, 25 May 2010; doi:10.1038/sj.bjc.6605708 www.bjcancer.com

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

Use of private gynaecologist does not relate to better prevention outcomes – An ecological analysis from Finland

BACKGROUND: Control of reproduction and prevention of reproductive health problems are important reasons for women to use health services, but the proper organisational level of service provision is not clear. The purpose of this study was to investigate whether visits to private gynaecologists correlate with better health outcomes and worse participation in organised screening for cancer programs. METHODS: This is an ecological analysis using municipalities and groups of women at 5-year age intervals within municipalities as study units. First, the Finnish municipalities (n = 452) were classified into three groups by the age-adjusted level of use of private gynaecologists. Secondly, each age group within municipalities was classified into tertiles by the level of private gynaecologist use. The outcomes were participation in cervical and organised breast cancer screening for cancer programmes, stage of gynaecological and breast cancers at diagnosis, and abortion rates and ratios. All data were obtained from national registers by groups at 5-year age intervals and by municipality. Raw and adjusted (age groups, and in some analyses, municipality social class index) odds ratios, total and by urbanity, were calculated. RESULTS: The proportions of women participating in cervical cancer and organised breast cancer screening for cancer were somewhat higher in the groups having a low use of private gynaecologists. The proportions of local cancers of all cervical, uterine, ovarian and breast cancers were similar in the three groups, even though the first analysis method suggested somewhat better results for the low-use group in case of cervical cancer and for the high-use group in case of uterine and breast cancer. The rates of induced abortion were higher in municipalities having a high use of private gynaecologists than in those having lower use. CONCLUSION: This ecological analysis suggests that frequent use of private gynaecologists relates somewhat to lower organised screening for cancer participation, and is not better in preventing abortions or in detecting cancer earlier. Our results suggest that a planned system relying mainly on general practitioners and public health nurses as the first line care providers is equally good for women's reproductive health as that in which specialists are used

The ‘Common Disease-Common Variant’ Hypothesis and Familial Risks

The recent large genotyping studies have identified a new repertoire of disease susceptibility loci of unknown function, characterized by high allele frequencies and low relative risks, lending support to the common disease-common variant (CDCV) hypothesis. The variants explain a much larger proportion of the disease etiology, measured by the population attributable fraction, than of the familial risk. We show here that if the identified polymorphisms were markers of rarer functional alleles they would explain a much larger proportion of the familial risk. For example, in a plausible scenario where the marker is 10 times more common than the causative allele, the excess familial risk of the causative allele is over 10 times higher than that of the marker allele. However, the population attributable fractions of the two alleles are equal. The penetrance mode of the causative locus may be very difficult to deduce from the apparent penetrance mode of the marker locus

Whole-exome sequencing identifies novel candidate predisposition genes for familial polycythemia vera

Background: Polycythemia vera (PV), characterized by massive production of erythrocytes, is one of the myeloproliferative neoplasms. Most patients carry a somatic gain-of-function mutation in JAK2, c.1849G > T (p.Val617Phe), leading to constitutive activation of JAK-STAT signaling pathway. Familial clustering is also observed occasionally, but high-penetrance predisposition genes to PV have remained unidentified. Results: We studied the predisposition to PV by exome sequencing (three cases) in a Finnish PV family with four patients. The 12 shared variants (maximum allowed minor allele frequency G (p.Phe418Leu) in ZXDC, c.1931C > G (p.Pro644Arg) in ATN1, and c.701G > A (p.Arg234Gln) in LRRC3. We also observed a rare, predicted benign germline variant c.2912C > G (p.Ala971Gly) in BCORL1 in all four patients. Somatic mutations in BCORL1 have been reported in myeloid malignancies. We further screened the variants in eight PV patients in six other Finnish families, but no other carriers were found. Conclusions: Exome sequencing provides a powerful tool for the identification of novel variants, and understanding the familial predisposition of diseases. This is the first report on Finnish familial PV cases, and we identified three novel candidate variants that may predispose to the disease.Peer reviewe