Methods
The Surveillance, Epidemiology, and End Results (SEER)
database12 was established by the National Cancer
Institute, covering approximately 28% of the US population. The Public
Use version of data collected from the SEER18
registries12 between January 1, 1973, and December 31,
2016, was used for this study. As a comparison, the mortality data of
the general US population collected by the National Centre for Health
Statistics spanning from 1969 to 2016 was used.
To avoid the influence of the second primary tumours on the outcome of
cancer patients, we only included patients diagnosed with the first
primary ovarian cancer at the beginning of this study. Patients were
excluded if the diagnosis was made at autopsy or obtained solely from
the death certificate, and those without definite data on age at
diagnosis, income, educational level, and survival time were also
excluded in this study (Supplementary Figure.1 ).
Available data about demographic characteristics from the SEER database
included age at diagnosis, race, and calendar year of diagnosis. The
tumour-related variables encompassed pathological type, stage, and
grade. Income (median family income) and educational level (percentage
of residents >25 years of age with at least a bachelor’s
degree) were categorized into quartiles. Residence types (rural/urban)
were obtained at the county level from the SEER program. Data on ovarian
cancer treatment, follow-up time, and cause of death were also
available. Ovarian cancer was categorized into five histological
subgroups according to the International Classification of Disease for
Oncology third revision (ICD-O-3) codes: type I epithelial, type II
epithelial, germ cell, sex cord-stromal, and other1314. Surgeries for ovarian cancer were categorized into
“Oophorectomy without hysterectomy”, “Oophorectomy with
hysterectomy”, “Surgery, not otherwise specified (NOS)”, “None”,
“Debulking”, and “Pelvic Exenteration”.
Patients with the following causes of death codes in the SEER database
were considered to have committed suicide: International Classification
of Diseases, Eighth Revision codes (ICD-8): 950-959; International
Classification of Diseases, Ninth Revision codes (ICD-9): 950-959; and
International Statistical Classification of Diseases and Related Health
Problems, Tenth Revision (ICD-10) codes U03, X60-X84, and Y87.0 and
recode 50220. Patients with the following causes of death codes in the
SEER database were considered to have committed accidental death: ICD-8:
800-949; ICD-9: 800-949; and ICD-10: V01-X59 and Y85-Y86 and recode
50210.
The number of suicides or accidental deaths divided by person-years of
survival was calculated as the mortality of suicidal or accidental
death. Among subgroups of cancer patients stratified by different
characteristics, SMRs were
calculated as the ratios of observed to expected number of
deaths5 15 6,
which provided the relative risk of death from suicide and accident
injury for cancer patients compared with all general US population with
the same distribution of age, sex, and race. The observed values
represented the number of suicides or accidental deaths in patients with
ovarian cancer, and the expected values represented the number of
individuals who died by suicide or accident in the general population. A
five-year age range was used for standardization, and the 95% CI of SMR
was determined by using the Poisson distribution approximation.
Interaction tests were further carried out to investigate the potential
differential effect of cancer subtypes on suicide risk during different
follow-up periods. Given that other causes of death were considered as
competing events, we also designed the Fine-Gray model to identify
demographic and tumour-related characteristics associated with a higher
risk of suicide and accidental death. Observations were censored if
patients did not die from suicide or accidental death at the time of the
last follow-up. The survival time recorded as 0 month in the SEER
database was converted to one-half of a month based on accepted
epidemiologic practices15.
All statistical tests were two-sided, and values with P<0.05
were considered statistically significant. The SEER database was
accessed using SEER*Stat software 8.3.812. The
calculation of SMRs, cumulative incidence curves, Gray tests, and
interaction tests were conducted in R version 3.51 statistical software.
These histograms summarizing the results of subgroup analyses were drawn
by Microsoft Excel and GraphPad Prism 8.0.