Cancer Risk

Weak evidence for an association between cannabis use and testicular germ cell tumors (>10 years of use), but no clear association found with head and neck, oral, or lung cancer.

Systematic review and meta-analysis on cannabis use and cancer risk; k=25 studies (19 case-control, 5 cohort, 1 cross-sectional study), published 1973–2019. Pooled analysis for 4 cancer types (lung, head and neck, oral squamous cell carcinomas, testicular germ cell tumors); ever use defined as ≥1 joint-year. Only 2 studies with low risk of bias; results reported as odds ratios with 95% CI.

Evidence of premalignant lung changes due to cannabis smoking, but no confirmed association with lung cancer after tobacco adjustment.

Systematic review (k=19 studies, Archives of Internal Medicine) on cannabis smoking and lung cancer risk. Biological plausibility demonstrated: increased tar exposure, alveolar macrophage dysfunction, increased oxidative stress, bronchial histopathology vs. tobacco smokers and non-smokers. However, observational studies showed NO significant association between cannabis smoking and lung cancer incidence after adjustment for tobacco use. Methodological limitations (selection bias, small sample sizes, young participant age with insufficient latency period). Conclusion: definitive statements on cancer risk not possible; educating patients about potential risks recommended.

Current, chronic and frequent cannabis use is associated with increased risk of testicular germ cell tumors, especially for non-seminomas (OR 2,59 for weekly use).

Systematic review and meta-analysis on cannabis exposure and testicular cancer risk; k=3 case-control studies (USA, predominantly 1990s data). Strongest association for non-seminomas: weekly cannabis use OR=2,59 (95% CI 1,60–4,19) vs. never-use; current, chronic and frequent use associated with development of testicular germ cell tumors. Inconclusive evidence for seminomas.

There is no statistically significant association between lifetime cannabis use and the occurrence of head and neck carcinomas.

Meta-analysis of k=9 case-control studies; ~12,6% of cases vs. 14,3% of controls were cannabis users; no association between lifetime cannabis use and head and neck cancer risk (OR=1,021; 95% CI 0,912–1,14; p=0,718).

Cannabis use consistently increases testicular cancer risk, but shows no clear association with lung or head-and-neck carcinomas.

Epidemiological review of 34 studies on cannabis and cancer risk (k=34): Testicular cancer risk increased — pooled OR=1,56 (95% CI 1,09-2,23) with frequent use, OR=1,50 (95% CI 1,08-2,09) with ≥10 years of use; lung cancer studies predominantly do not support an association; insufficient data for other cancer sites.

Genetic predisposition for lifetime cannabis use was associated with increased risk of squamous cell carcinoma (OR = 1,22, p = 0,003).

Two-sample Mendelian randomization on genetic predisposition for cannabis use and lung cancer risk (data: International Cannabis Consortium n=184.765, International Lung Cancer Consortium 29.266 cases + 56.450 controls). Genetic liability for lifetime cannabis use associated with increased risk of squamous cell carcinoma (OR=1.22, 95% CI 1.07–1.39, p=0.003, q=0.025). No association for other lung cancer subtypes; pleiotropy analyses unremarkable.

Indications of increased cancer risk for several cancer types (especially testicular tumors), but evidence is suggestive rather than conclusive.

Umbrella review on cancer risk evidence with cannabis legalization in the USA. Strongest association for non-seminomatous testicular cancer; emerging evidence for increased risk of lung squamous cell carcinoma, head-neck tumors, oral, breast, liver, cervical, laryngeal, pancreatic, thyroid and childhood cancer. Overall finding: suggestive, not conclusive; methodological limitations (confounder bias, misclassification) identified.

Non-significant trend towards reduced overall cancer risk (RR=0,90, p>0,06); after exclusion of selection and performance bias significantly reduced risk (RR=0,86, p<0,017); head and neck carcinomas showed significant risk reduction (RR=0,83), but high heterogeneity and low confidence in the results.

Scoping review with meta-analysis on cannabis use and cancer risk in the USA; k=34 studies (50 data points with risk ratios). Overall RR=0,90 (p>0,06, not significant, high heterogeneity I²=72,4%). After removal of studies with high selection/performance bias: RR=0,86 (p<0,017, Hedges g=0,66; N=24 data points), but still high heterogeneity (I²=74,9%). Testicular tumour: the only cancer type with RR>1 (RR=1,12, p=0,3, not significant). Head and neck carcinomas: negative association (RR=0,83, p<0,05, Hedges g=0,55). Data consistent with a negative association between cannabis use and non-testicular cancers, but low confidence due to high heterogeneity.

Cannabis use showed a significant but very small risk contribution for cervical cancer as well as weak indications for laryngeal and breast cancer; for the remaining cancer types no association was found.

Two-sample Mendelian Randomization on cannabis use and 9 cancer types (GWAS data, European ancestry). Significant causal association for cervical carcinoma (OR=1.001265, 95% CI 1.000375–1.002155, p=0.0053); suggestive evidence for laryngeal carcinoma (OR=1.000350, p=0.0336) and breast cancer (OR=1.003741, p=0.0467). No association with melanoma, colorectal, oral, esophageal carcinoma or glioma.

Moderate cannabis use was associated with a markedly reduced risk of head and neck squamous cell carcinoma.

Population-based case-control study (n=434 HNSCC cases, n=547 controls, Boston MA); 10–20 years of cannabis use vs. never-users: significantly reduced HNSCC risk (OR=0,38, 95% CI 0,22–0,67); moderate weekly use also associated with reduced risk (OR=0,52, 95% CI 0,32–0,85); trend p<0,001; inverse association independent of HPV-16 antibody status.

Cannabis use is an independent risk factor for HPV-16-positive, but not for HPV-16-negative head and neck cancers.

Case-control study (n=240 HNSCC cases, n=322 controls): Cannabis use was independently associated with HPV-16-positive head and neck squamous cell carcinoma — increasing dose-dependently with intensity (joints/month, p(trend)=0,007), duration (years, p(trend)=0,01) and cumulative joint-years (p(trend)=0,003). For HPV-16-negative HNSCC no association with cannabis use (OR not significant). Findings suggest cannabis-associated cancer risk specifically in the HPV-16-positive HNSCC subtype.

Monthly cannabis use was associated with a significantly increased risk of malignant primary glioma (RR 2,8).

Prospective cohort study (n=133.811, Kaiser Permanente, up to 21 years follow-up); cannabis use ≥1x/month associated with 2,8-fold increased glioma risk (CI=1,3–6,2), adjusted for cigarette smoking, alcohol, age, sex, ethnicity. No dose-response relationship demonstrable. Increased risk among women for cigarette smoking (p-for-trend=0,04), not in men.

No generally increased cancer risk from cannabis use, but indications of increased prostate and cervical cancer risk in those abstinent from tobacco nicotine.

Retrospective cohort study (n=64.855, mean follow-up 8,6 years): Cannabis use overall was not associated with increased cancer risk (RR=0,9 [95% CI 0,7–1,2] men; RR=1,0 [0,8–1,1] women). In non-smokers, cannabis use was associated with increased prostate cancer risk (RR=3,1 [95% CI 1,0–9,5]) and a tendency toward increased cervical cancer risk (RR=1,4 [95% CI 1,0–2,1]). No association with tobacco-related or colorectal cancers.

There was no significant association between habitual cannabis smoking and lung cancer risk, although a possible effect at very high consumption cannot be excluded.

Pooled analysis k=6 case-control studies (International Lung Cancer Consortium), n=2.159 lung cancer cases + 2.985 controls; habitual vs. never use OR=0.96 (95% CI: 0.66–1.38); ≥1 joint/day OR=0.88 (95% CI: 0.63–1.24); ≥10 joint-years OR=0.94 (95% CI: 0.67–1.32). Adenocarcinoma OR=1.73 (95% CI: 0.75–4.00). Result: little evidence for increased lung cancer risk from cannabis smoking; a weak positive association with cumulative use cannot be excluded.

No significant association between cannabis use and lung or aerodigestive tract cancer risk after adjustment for confounding.

Case-control study (n=1.212 cancer cases + n=1.040 controls) on cannabis use and lung/aerodigestive tumors; after adjustment for cigarette smoking no increased risk: aOR lung cancer ≥60 joint-years vs. 0 = 0.62 [95%-CI 0.32–1.2]; aOR oral cancer = 1.1 [95%-CI 0.56–2.1]. No consistent dose-response relationship.

Current cannabis use is associated with an increased risk of nonseminoma TGCT, with early onset of use and high frequency of use further increasing the risk.

Population-based case-control study (n=369 testicular germ cell tumor cases, n=979 age-matched controls); current cannabis use was associated with increased TGCT risk (OR=1,7; 95%-CI 1,1–2,5); for nonseminoma/mixed histology OR=2,3 (95%-CI 1,3–4,0); daily/weekly use OR=3,0; first use <18 years OR=2,8.

Cannabis use was associated with reduced bladder cancer incidence, whereas tobacco use was associated with increased risk.

Prospective cohort study (n=84.170 men, 11 years follow-up): cannabis-only use associated with a 45% reduction in bladder cancer incidence vs. non-users (HR=0,55; 95% CI 0,31–1,00). Tobacco-only use, in contrast, with increased risk (HR=1,52; 95% CI 1,12–2,07). 279 (0,3%) bladder tumors in total; p<0,001 for frequency comparison.

Heavy cannabis use was associated with a more than twofold increase in risk for lung cancer over 40 years.

n=49.321 Swedish men (age 18–20 y.), 40-year follow-up; heavy cannabis use (>50 times lifetime, n=831) was significantly associated with more than double the risk of lung cancer (HR=2,12; 95% CI 1,08–4,14), even after adjustment for tobacco use, alcohol, respiratory diseases and socioeconomic status.

Cannabis use was not associated with an increased risk of oral squamous cell carcinoma in this population-based study.

Population-based case-control study (n=407 OSCC cases + n=615 controls), cannabis use and risk of oral squamous cell carcinoma: adjusted OR=0,9 (95% CI 0,6–1,3), no increased risk. No trend with increasing duration of use, frequency, or time since first use. No subgroup effect (age, smoking, alcohol, genetic polymorphisms).

Cannabis smoking significantly increases the lung cancer risk in a dose-dependent manner, independent of cigarette smoking.

Case-control study (79 lung cancer cases, 324 controls, age ≤55 yrs, New Zealand): Lung cancer risk increased by 8% per joint-year of cannabis use (95% CI 2-15), adjusted for cigarette smoking; highest tertile of cannabis use: RR=5,7 (95% CI 1,5-21,6) vs. non-users.

Cannabis and tobacco cause additive bronchial mucosal damage, whereas cocaine alone produces lesser changes, but intensifies tobacco-induced damage.

Cohort study (n=241) with bronchoscopy biopsies; cannabis smokers (n=40) showed significantly more histopathological mucosal changes than non-smokers in all 11 characteristics (p≤0,02); cannabis use and tobacco smoking show additive bronchial mucosal damage (MTS group); cocaine alone causes fewer changes than cannabis.

Lifetime cannabis use was associated with a reduced risk of non-Hodgkin lymphoma.

Population-based case-control study (n=1.281 NHL cases, n=2.095 controls) on non-Hodgkin lymphoma risk factors in the San Francisco Bay Area 1988–1995; in multivariate analysis, lifetime cannabis use was associated with a significantly reduced NHL risk (direction: negative risk; OR <1,0 in the final model).

Cannabis use doubles the risk for non-seminoma of the testis (OR 2,42), while cocaine is inversely associated.

Case-control study (163 testicular cancer cases, 292 controls, Los Angeles County 1986–1991). Ever cannabis use: OR=1.94 (95%-CI 1.02–3.68) for testicular germ cell tumor overall; specifically non-seminoma/mixed tumors OR=2.42 (95%-CI 1.08–5.42). Adjusted for cryptorchidism, education, religiosity, cocaine. No increased overall risk for seminoma.

Frequent cannabis use is associated with an approximately 2-fold increased TGCT risk, for nonseminomas increased up to 3-fold.

Hospital-based case-control study (n=187 testicular tumor cases, n=148 controls); frequent cannabis use (daily or more) vs. non-users OR=2,2 (95%-CI 1,0–5,1) for germ cell tumors overall; for non-seminoma: frequent use OR=3,1 (95%-CI 1,2–8,2); long-term use (≥10 years) OR=2,4 (95%-CI 1,0–6,1).

Cannabis use did not significantly increase the risk of head and neck carcinoma (RR=1,6; 95%-CI 0,5–5,2).

Case-control study (75 cases, 319 controls, ≤55 years): highest tertile of cannabis use (>8.3 joint-years) was not significantly associated with increased head and neck cancer risk (RR=1.6, 95% CI 0.5–5.2, not significant after confounder adjustment). No statistically significant association between cannabis use and head and neck carcinoma; limited statistical power does not rule out a small long-term effect.

Habitual cannabis use was significantly associated with the occurrence as well as with the stage, grade, and recurrence frequency of urothelial carcinoma.

n=52 men <60 years of age with transitional cell carcinoma (TCC) vs. n=104 age-matched controls. 88,5% of TCC patients reported habitual cannabis use vs. 69,2% of controls (P=0.008). Cannabis use correlated significantly with tumor stage, grade, and recurrence frequency within the TCC group. Indication of increased TCC risk from cannabis smoking.

Cannabis smoking causes a markedly higher respiratory burden of CO and tar compared to tobacco.

n=15 men with long-term cannabis and tobacco use (≥5 years); cannabis smoking vs. tobacco: ~5-fold higher increase in blood carboxyhemoglobin, ~3-fold more inhaled tar, 1/3 more tar retention in the respiratory tract (p<0.001); puff volume ~2/3 larger, inhalation depth 1/3 greater, breath-hold duration ~4-fold longer (p<0.01) — independent of THC content. Increased respiratory pollutant burden (carbon monoxide, tar); a direct cancer risk is not demonstrated.