Inverse birth cohort effects in ovarian cancer: Increasing risk in BRCA1/2 mutation carriers ....

Inverse birth cohort effects in ovarian cancer: Increasing risk in BRCA1/2 mutation carriers and decreasing risk in the general population
  

Highlights

•

Breast cancer risk increases with more recent birth cohorts, while results for ovarian cancer are inconsistent.

•

Birth cohort effects in ovarian cancer in BRCA mutation carriers and the general population were studied.

•

Ovarian cancer risks increase with birth cohort in BRCA carriers and decrease in the general population. The reason is unknown.

Objective

BRCA1/2 carriers are at increased risk of ovarian cancer, and some reports suggest an increasing risk in more recent birth cohorts. In contrast, decreasing incidences have been observed in the general population. The aim was to assess the birth cohort effect on ovarian cancer risk in BRCA1/2 carriers relative to their background general population.

Methods

Data on ovarian cancer incidence was collected for a cohort of 1050 BRCA1/2 mutation carriers ascertained by our regional clinic and retrieved from the general Dutch population cancer registry. Birth cohorts were categorized as pre-1935, 1935–1953, post-1953. Birth cohort effects on the ovarian cancer risk were estimated using hazard ratios (HRs) in BRCA1/2 carriers and Poisson rate ratios in the general population. Standardized incidence ratios (SIRs) were calculated to compare populations. HRs were adjusted for mutation position and family history.

Results

Compared to the pre-1935 cohort, BRCA1 carriers in the 1935–1953 and post-1953 cohorts had an increased ovarian cancer risk of HR_adjusted 1.54 (95% CI 1.11–2.14) and 2.40 (95% CI 1.56–3.69), respectively. BRCA2 carriers in the 1935–1953 cohort had an HR_adjusted of 3.01 (95% CI 1.47–6.13). The SIRs for the 1935–1953 and post-1953 cohorts were 1.7 and 2.7, respectively, for the BRCA1 carriers and 1.6 times and 2.4 times, respectively, for BRCA2 carriers.

Conclusions

Mutation carriers, particularly BRCA1 carriers, born in the most recent cohorts, have the highest additional ovarian cancer risk as compared to the general population.