Oral Contraceptives: A Risk Factor for Squamous Cell Carcinoma?

Abstract

Oral contraceptives (OCs) affect the risk of several cancers in women, but have been virtually unstudied for squamous cell carcinoma (SCC). We examined the hypothesis that OCs influence SCC risk in a case–control study among women and also examined whether polymorphisms in the DNA repair gene, Xeroderma pigmentosum group D (XPD), modified the risk. Incident cases of SCC were identified by a network of dermatologists and pathology laboratories. Population-based controls were frequency matched to cases by age and gender (n = 261 SCC cases, 298 controls). Overall, OC use was associated with a 60% higher risk of SCC (odds ratio (OR), 1.6; 95% confidence interval (95% CI): 1.0–2.5). ORs for SCC were higher among those who last used OCs ≥25 years before diagnosis (OR: 2.1; 95% CI: 1.2–3.7), and among these women, SCC risk increased with duration of use (OR for ≤2 years, 1.7; 95% CI: 0.9–3.5; OR for 3–6 years, 2.6; 95% CI: 1.0–6.5; OR for ≥7 years, 2.7; 95% CI: 0.9–8.5, Ptrend = 0.01). Furthermore, the XPD Lys751Gln polymorphism was a significant modifier of the OC-SCC association (Pinteraction = 0.03). These findings lead us to hypothesize a potential relationship between OCs and SCC risk, and that this could involve DNA repair pathways.

Does hormone replacement therapy and use of oral contraceptives increase the risk of non-melanoma skin cancer?

“…Hence, alterations in the DNA repair capacity (DCR) also affect the risk of NMSC [38]. Some studies have suggested that estrogen can affect DCR levels in women [20,23,25]. Another potential biological mechanism was suggested by Welsh et al [21].…”

“…Two studies, a case-control by Wei et al [25] and a cohort study by Vessey et al [24], reported no association between use of OC and NMSC, whereas three recent case-control studies all indicated that use of OC may increase the risk of SCC. Asgari et al [22] found a twofold increased SCC risk among women who used OCs in the past year before SCC diagnosis, and Applebaum et al [23] reported a 60% increased risk of SCC among ever OC users compared with never users. Furthermore, Applebaum et al [23] showed that polymorphisms in the DNA repair gene Xeroderma pigmentosum D (XPD) significantly affected the association between OC use and risk of SCC.…”

“…Asgari et al [22] found a twofold increased SCC risk among women who used OCs in the past year before SCC diagnosis, and Applebaum et al [23] reported a 60% increased risk of SCC among ever OC users compared with never users. Furthermore, Applebaum et al [23] showed that polymorphisms in the DNA repair gene Xeroderma pigmentosum D (XPD) significantly affected the association between OC use and risk of SCC. Likewise, results by Welsh et al [21] indicated a possible gene-environment effect, as the variant Histidine ammonia-lyase (HAL) genotype seemed to modify the risk of SCC associated with OC use.…”

“…Even though both OC and HRT are biologically plausible risk factors for NMSC, as several hypothesis explains how these exogenous hormones may act in conjunction with known pathways in the NMSC carcinogenesis [20][21][22][23], only few epidemiological studies have examined these associations [21][22][23][24][25]. Two studies, a case-control by Wei et al [25] and a cohort study by Vessey et al [24], reported no association between use of OC and NMSC, whereas three recent case-control studies all indicated that use of OC may increase the risk of SCC.…”

Epidemiology and Outcomes of Cutaneous Squamous Cell Carcinoma

“…A large prospective cohort study investigating the risk of incident SCC in white women found that those in the highest quartile of plasma 25(OH) vitamin D levels had more than a threefold increased risk of SCC as compared to women with plasma 25(OH) vitamin D levels in the lowest quartile [ 171 ]. Another prospective study found that those with serum 25(OH) vitamin D concentrations above 75 nmol/L had a lower risk of SCC incidence as compared to those with serum 25(OH) vitamin D concentrations below 75 nmol/L [ 172 ]. Several other studies have found no associations between serum vitamin D level and SCC incidence [ 173 , 174 ].…”