Multiple sclerosis (MS) and cancer present substantial global health challenges. Understanding cancer patterns among people with MS (PwMS) is crucial due to potential variations across demographics and geographic regions. Isfahan province in Iran, known for its high MS incidence ratio, offers a significant population for comprehensive studies on MS. In this study, we aim to investigate the association between risk of cancer and MS. Data on PwMS were collected utilizing the National Multiple Sclerosis Registry System of Iran (NMSRI), with diagnoses confirmed using McDonald criteria by neurologists specialized in MS. Cancer incidence was investigated using the Iranian National Population-Based Cancer Registry (INPCR) data, collected following international protocols. Descriptive statistics and regression analyses were employed to assess factors associated with cancer and mortality risks among PwMS. Survival analysis was conducted using Kaplan-Meier curves. Out of 10,049 PwMS, 123 were diagnosed with cancer, with an mean age at the time of cancer diagnosis being 40.41 years and a mean MS duration of 6.76 years. The majority had relapsing-remitting MS (81.2%), and Interferon-β was the most common disease-modifying therapy (DMT) (42.4%). Cancer incidence was 125.6 per 100,000 person-years, peaking at ages 60-64 (677.9 per 100,000 person-years). Receiving monoclonal antibody medications and older age were significantly associated with higher cancer risk (OR:1.542 (1.009-2.357), OR:1.033 (1.015-1.051), respectively). Female breast cancer had the highest incidence ratio among PwMS (40.17 per 100,000 person-years), followed by thyroid (18.38 per 100,000 person-years) and digestive system cancers (17.36 per 100,000 person-years). Breast cancer was the predominant cancer in women, while digestive system cancers were most common among men. Being male and having longer MS duration were linked to higher cancer mortality risk (HR: 2.683, 1.087, respectively). Cancer incidence among 10,049 people with multiple sclerosis was significant, especially in older individuals, with breast cancer being the most common. Male gender and longer MS duration were linked to higher cancer mortality risk.
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