Risk of second primary cancer associated with pre-diagnostic smoking, alcohol, and obesity in women with keratinocyte carcinoma

Abstract

Keratinocyte carcinoma (KC), which includes basal-cell carcinoma (BCC) and squamous-cell cancer (SCC), has been associated with an increased risk of second primary cancers (SPCs), although the reason for this increase is unknown. We assessed the effects of smoking, alcohol, and obesity prior to the diagnosis of KC on the development of SPCs, as these are well-established risk factors for multiple cancers and may also contribute to the increased risk of SPCs among those with KC. A total of 15,628 women with self-reported KC were identified in the Nurses’ Health Study. Incident SPCs were assessed throughout the follow-up until June 2012. Cox proportional hazards models were used to calculate the hazard ratios (HRs) of SPC associated with pre-diagnostic smoking, alcohol and body mass index (BMI). We also compared these risk estimates to those for first cancers in all cohort participants. During 193,695 person-years of follow-up, we recorded 2839 SPC cases. Compared with never smokers, current smokers had a significantly elevated risk for SPC overall and specifically for lung, colorectal, and bladder cancers. We also found a positive association between higher BMI and risk for SPC overall as well as for endometrial and bladder SPCs. Women with KC who consumed alcohol ≥30 g/day had a marginally higher risk of SPC compared to non-drinkers. The associations between incident SPC risk among KC cases and smoking, alcohol, and obesity appeared similar to the associations between these risk factors and the incident first primary cancers in the whole cohort. Only in the heavy smoking (≥25 cigarettes/day) category was the HR for SPC after KC (2.34; 95% CI 1.98–2.76) slightly higher than that for the first cancer in the overall cohort (HR 1.86; 95% CI 1.75–1.98, Pheterogeneity = 0.01). In conclusion, pre-diagnostic smoking, alcohol and obesity prior to KC diagnosis were associated with risk of SPCs.

Association Between Alcohol Consumption and Risk of Bladder Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies

“…5 cohorts were conducted in the USA, 3 cohorts were conducted in Europe, and 1 cohort was conducted in Japan. 2 studies ( 28 , 29 ) included males only while another 2 studies ( 32 , 33 ) just considered females. All studies were considered high quality (NOS scores≧7).…”

“…2,714 records were excluded after reviewing titles and abstracts, leaving 84 papers for the full-text check. Finally, 75 studies were excluded and a total of 9 prospective cohort studies were enrolled (10,11,(27)(28)(29)(30)(31)(32)(33). Titles of excluded articles after full-text check were provided in Supplementary Table 1.…”

“…Data of multiple levels of alcohol exposure in another 7 studies were then converted into dichotomous levels (any versus none) indirectly to explore the risk differences between alcohol consumers and non-drinkers. Firstly, 8 studies (10,11,27,28,(30)(31)(32)(33) were included to pool the risk estimates of any alcohol intake versus none. And the results showed no significantly changed risk of bladder cancer in alcohol consumers, but the heterogeneity was significant (RR=1.07; 95%CI: 0.95-1.20; I 2 =65.3%) (Figure 2).…”

“…To conduct the dose-response meta-analysis, alcohol units in two studies were converted from "drink" to "gram" based on the criteria self-reported in each study respectively while the pure alcohol amount from different alcoholics in two studies (28,29) was calculated based on pre-set concentration standard (21) for further subgroup analysis. Firstly, 7 studies were pooled for doseresponse relationship exploration without alcohol type and gender restrictions (10,11,28,(30)(31)(32)(33). However, there was no evidence of a linear (P linear =0.11, Figure 5A) or nonlinear (P nonlinear =0.28, Figure 5B) association between alcohol consumption and risk of bladder cancer.…”

Prediagnosis alcohol intake and metachronous cancer risk in cancer survivors: A prospective cohort study

“…Prediagnosis smoking 26 and body fatness 26‐28 are known risk factors for metachronous cancer. The role of alcohol has not been studied broadly: it has been shown to increase slightly the risk of metachronous cancer in women with keratinocyte carcinoma in the Nurses' Health Study 29 and in patients with primary UADT cancer in a meta‐analysis of eight cohort and 11 case‐control studies 30 ; alcohol intake did not increase metachronous colorectal cancer risk in individuals with colorectal cancer in the Colon Cancer Family Registry 31 ; and findings for patients with primary breast cancer were inconclusive 32 . The International Agency for Research on Cancer classified acetaldehyde, the first and most toxic metabolite of ethanol found in alcoholic beverages and produced in the liver, as carcinogenic to humans 33 .…”