FANCM c.5101C > T mutation associates with breast cancer survival and treatment outcome

Breast cancer (BC) is a heterogeneous disease, and different tumor characteristics and genetic variation may affect the clinical outcome. The FANCM c.5101C> T nonsense mutation in the Finnish population associates with increased risk of breast cancer, especially for triple-negative breast cancer patients. To investigate the association of the mutation with disease prognosis, we studied tumor phenotype, treatment outcome, and patient survival in 3,933 invasive breast cancer patients, including 101 FANCM c.5101C> T mutation carriers and 3,832 non-carriers. We also examined association of the mutation with nuclear immunohistochemical staining of DNA repair markers in 1,240 breast tumors. The FANCM c.5101C>T mutation associated with poor 10-year breast cancer-specific survival (hazard ratio (HR) 51.66, 95% confidence interval (CI) 1.09-2.52, p=0.018), with a more pronounced survival effect among familial cases (HR=2.93, 95% CI 1.5-5.76, p=1.80 x 10 23). Poor disease outcome of the carriers was also found among the estrogen receptor (ER) positive subgroup of patients (HR=1.8, 95% CI 1.09-2.98, p=0.021). Reduced survival was seen especially among patients who had not received radiotherapy (HR=3.43, 95% CI 1.6-7.34, p=1.50x10(-3)) but not among radiotherapy treated patients (HR=1.35, 95% CI 0.82-2.23, p=0.237). Significant interaction was found between the mutation and radiotherapy (p=0.040). Immunohistochemical analyses show that c.5101C> T carriers have reduced PAR-activity. Our results suggest that FANCM c.5101C>T nonsense mutation carriers have a reduced breast cancer survival but postoperative radiotherapy may diminish this survival disadvantage.Peer reviewe

The Association Between Compulsory School Achievement and Problem Gambling Among Swedish Young People

Purpose: We aimed to examine the association between school grades at the age of 16 years and problem gambling at the age of 17-25 years among Swedish females and males. Methods: In a cohort design, we followed the 16-to 24-year-old participants in the representative Swedish Longitudinal Gambling Study for 2 years, 2008/2009 and 2009/2010, generating 3,816 person-years of follow-up time. The outcome, incidence of mild and moderate/severe gambling problems, was measured by the Problem Gambling Severity Index in telephone interviews. The exposure was register-linked information about final grades in compulsory school. The association between school grades and problem gambling was estimated in multinomial logistic regressions. Results: Low and average school grades were associated with increased incidence of mild and moderate/severe problem gambling compared to high grades, adjusted for sociodemographic characteristics, psychological distress, and alcohol use. Low grades, compared to high grades, were associated with a higher risk of mild gambling problems for adolescent males, whereas the incidence proportion of moderate/severe problem gambling was high for males aged 20-25 years with low grades, among whom unemployment was also very high. Furthermore, we found a strong and graded association between school grades and moderate/severe problem gambling for women in both age groups, despite a low prevalence of gambling participation among females compared to males. Conclusions: Our findings show that Swedish youth with low school achievement have an increased risk of gambling problems up to 8 years after school graduation, after control for confounding from sociodemographic characteristics, psychological distress, and alcohol use, and that this association is stronger for females than males

The Association Between Compulsory School Achievement and Problem Gambling Among Swedish Young People

Purpose: We aimed to examine the association between school grades at the age of 16 years and problem gambling at the age of 17-25 years among Swedish females and males. Methods: In a cohort design, we followed the 16-to 24-year-old participants in the representative Swedish Longitudinal Gambling Study for 2 years, 2008/2009 and 2009/2010, generating 3,816 person-years of follow-up time. The outcome, incidence of mild and moderate/severe gambling problems, was measured by the Problem Gambling Severity Index in telephone interviews. The exposure was register-linked information about final grades in compulsory school. The association between school grades and problem gambling was estimated in multinomial logistic regressions. Results: Low and average school grades were associated with increased incidence of mild and moderate/severe problem gambling compared to high grades, adjusted for sociodemographic characteristics, psychological distress, and alcohol use. Low grades, compared to high grades, were associated with a higher risk of mild gambling problems for adolescent males, whereas the incidence proportion of moderate/severe problem gambling was high for males aged 20-25 years with low grades, among whom unemployment was also very high. Furthermore, we found a strong and graded association between school grades and moderate/severe problem gambling for women in both age groups, despite a low prevalence of gambling participation among females compared to males. Conclusions: Our findings show that Swedish youth with low school achievement have an increased risk of gambling problems up to 8 years after school graduation, after control for confounding from sociodemographic characteristics, psychological distress, and alcohol use, and that this association is stronger for females than males