Effect of family history of cancer on postoperative survival in patients with non-small cell lung cancer

Introduction

Lung cancer is the leading cause of cancer-related deaths worldwide, including non-small cell lung cancer (NSCLC), and small cell lung cancer (1). NSCLC mainly compromises of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Surgery is the only curative treatment regimen in patients with early-stage lung cancer. However, postoperative survival of lung cancer patients is not promising. Identifying prognostic factors and interfering timely are essential for improving survival.

Family history of cancer (FHC) is related to increased cancer mortality (2-5), and family history of lung cancer (FH-LC) is regarded as a risk factor of lung cancer carcinogenesis (1,6). Previous studies have reported that FHC is a prognostic factor in some solid tumors, such as breast cancer (7), colorectal cancer (8), and prostate cancer (9). In LUAD patients, a previous study indicated that FH-LC had no impact on postoperative recurrence, while family history of non-lung cancer (FH-nLC) was associated with increased risk of recurrence and death (10). FH-LC was also reported to have no impact on postoperative survival (11). However, another study reported that lung cancer patients with FH-LC had a poorer outcome than those without (12).

Difference cancer type of FHC is correlated with different genomic features (10,13), which means FHC might have different prognostic effect on lung cancer with different histology type. In LUSC patients, familial aggregation has also been observed, and FHC has been identified as a risk factor of cancer onset and progression (14,15). However, few studies focused on the relationship between FHC and the prognosis of LUSC patients. We herein conducted this study to identify the effect of FHC on postoperative survival in the patients with LUAD or LUSC. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-349/rc).

Methods

Study design and data source

This study was a retrospective cohort study of patients undergoing lung resection for LUAD or LUSC. The report of this study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology statement (16).

Patient data were gathered and extracted from a prospectively established database. This study was approved by the Ethics Committee of West China Hospital of Sichuan University (No. 2022-641), and the requirement for informed consent was waived due to the retrospective nature of this study. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).

Population

The patients with LUAD or LUSC who underwent lung resection at the Department of Thoracic Surgery, West China Hospital between March 2009 and February 2021 were enrolled.

Inclusion criteria included: (I) older than 18 years old; (II) completing the self-reporting interview questions about their FHC; (III) pathological diagnosed with LUSC or LUAD; (IV) undergoing lung resection.

Exclusion criteria included: (I) emergency operations; (II) operations discontinued due to severe tumor adhesion; (III) identified as stage 0 by postoperative pathology; (IV) death within one month; (V) lack of detailed family history and follow-up information.

Data collection

Data collection included age, sex, smoking history, FHC, percentages for forced expiratory volume in 1 second of predicted values (FEV1%), percentages for diffusing capacity of the lungs for carbon monoxide of predicted values (DLCO%), comorbidity, type of surgery [video-assisted thoracic surgery (VATS) and thoracotomy], extent of resection (pneumonectomy, lobectomy, segmentectomy, wedge resection), clinicopathological feature of tumor (tumor size, pathological type, pathological stage), adjuvant therapy and FHC, as well as with survival data. FHC was defined as a self-reported FHC in first-degree (parents, offspring, siblings).

Outcomes

The primary outcome was overall survival (OS), defined as the date from lung cancer surgery to death or last follow-up. The secondary outcomes were progression-free survival (PFS) and lung cancer-specific survival (LCSS). PFS was calculated from the date of surgery until first relapse (radiologic findings or histologic confirmation) or death or the last follow-up. LCSS was defined as the interval between surgical resection to death owing to lung cancer other than other causes.

Treatment and follow-up

Preoperative evaluation for patients was mainly conducted through pulmonary function tests, high-resolution chest computed tomography (CT). All patients received anatomic lung resection and systematic or specific lymph node dissection, by VATS or thoracotomy. Three-port or uniportal VATS was performed using the single-direction thoracoscopic lobectomy technique as our center previously reported (17). Postoperative management and follow-up were conducted according to clinical practice. Follow-up method included outpatient visit, online clinic, and telephone.

Sample size estimation

Considering OS as the primary outcome, one prior literature reported that the quantity ratio of the FH-nLC and non-FHC was about 1:3, the hazard ratio (HR) of FH-nLC reached 1.65 compared to non-FHC (10). The alpha level was set as 0.05, with the power of the test of 0.9. The rate of loss of follow-up was assumed as 5%. Therefore, the minimal total sample size of this study would be 263 calculated by the software PASS (Version 15.0.5), with 65 cases in FHC group and 198 in non-FHC group.

Statistical analysis

The mean and standard deviation were used to describe measurement data with normal distribution. The median with interquartile range (IQR) was used to describe enumeration data. The former data would be analyzed using the Student’s t-test while the latter would be analyzed using Pearson’s chi-square test or Fisher’s exact. OS, LCSS, and PFS were estimated via Kaplan-Meier method and survival curve was then plotted. Log-rank test was used to assess the survival difference between the groups. Univariate and multivariate analyses were performed through Cox regression model, with the HR and the corresponding 95% confidence intervals (CIs) calculated. All tests are two-sided tests. P value <0.05 was considered as statistically significant. All data were analyzed using R version 4.1.1 software (The R Foundation for Statistical Computing, 2021).

Results

Baseline characteristics

A total of 6,253 patients were enrolled, including 5,685 LUAD and 568 LUSC (Figure 1). Altogether 18.9% (1,077/5,685) patients had FHC in LUAD, and 12.7% (72/568) patients had FHC in LUSC. There was no significant difference of most baseline characteristics between two groups (Table 1). Only one relative has cancer was observed in 82.82% LUAD patients with FHC, while 91.67% LUSC patients with FHC (Table 2). The most frequent types of cancer were lung cancer, esophagus cancer, liver cancer, gastric cancer, and colorectal cancer.

Figure 1 Flow chart of patient selection. LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; FHC, family history of cancer.

Impact of FHC on survival

In LUAD, the patients with FHC showed comparable survival compared with the patients without FHC regarding 5-year OS [87.9% (95% CI: 83.9–92%) vs. 86.5% (95% CI: 84.4–88.7%), P=0.49] (Figure 2A), 5-year PFS [84.8% (95% CI: 80.8–88.9%) vs. 80.9% (95% CI: 78.8–83%), P=0.06] (Figure 2B), and 5-year LCSS [89.2% (95% CI: 85.6–93.1%) vs. 88.0% (95% CI: 85.9–90.2%), P=0.96] (Figure 2C).

Figure 2 Kaplan-Meier survival curves for patients with and without FHC in LUAD patients after lung resection. (A) OS. (B) PFS. (C) LCSS. FHC, family history of cancer; OS, overall survival; HR, hazard ratio; CI, confidence interval; PFS, progression-free survival; LCSS, lung cancer-specific survival; LUAD, lung adenocarcinoma.

In LUSC, the patients with FHC had poorer survival compared with the patients without FHC according to 5-year OS [40.9% (95% CI: 27.1–67.1%) vs. 68.2% (95% CI: 63–74.1%), P=0.007] (Figure 3A), 5-year PFS [42.3% (95% CI: 29.2–61.3%) vs. 66.2% (95% CI: 61.3–71.5%), P=0.003] (Figure 3B), and 5-year LCSS [45.8% (95% CI: 31.8–66%) vs. 72.7% (95% CI: 67.5–78.2%), P=0.003] (Figure 3C).

Figure 3 Kaplan-Meier survival curves for patients with and without FHC in LUSC patients after lung resection. (A) OS. (B) PFS. (C) LCSS. FHC, family history of cancer; OS, overall survival; HR, hazard ratio; CI, confidence interval; PFS, progression-free survival; LCSS, lung cancer-specific survival; LUSC, lung squamous cell carcinoma.

Multivariate analysis

In multivariate analysis, FHC was not an independent prognostic factor of OS (HR =1.11; 95% CI: 0.80–1.54; P=0.52), PFS (HR =0.96; 95% CI: 0.75–1.23; P=0.72), and LCSS (HR =1.23; 95% CI: 0.87–1.73; P=0.24) in the patients with LUAD (Table S1).

While FHC was found to be an independent prognostic factor of OS (HR =2.16; 95% CI: 1.35–3.44; P=0.001), PFS (HR =2.06; 95% CI: 1.34–3.17; P=0.001), and LCSS (HR =2.32; 95% CI: 1.42–3.78; P=0.001) in the patients with LUSC (Table S2).

Discussion

Our study indicated that LUSC patients who had a FHC in a first-degree relative experienced a negative impact on their survival following lung resection, not only on OS, but also on LSCC and PFS. While no significant impact of FHC was observed in LUAD patients.

Several previous studies have reported the association between FHC and prognosis of lung cancer. The study from Ganti et al. showed that the patients with lung cancer tended to get worse OS outcomes if they had relatives with cancer, specifically first-degree relatives (12). However, other studies reported the contrary results. Li et al. reported that patients with positive FHC were diagnosed at earlier age and at more advanced tumor stage than patients without FHC, but had decreased risk of death (18). Isla et al. also reported a higher median OS of FHC group than non-FHC group in the Spanish women cohort (19). There are some possible explanations for why several studies indicated that FHC would improve prognosis for patients with lung cancer. One might be that patients would concern more about good living habits like staying away from smoking if their relatives have developed cancer. People may also be more sensitive to smoke especially second- or third-hand smoke if their co-resident or relatives have a smoking habit. Another possible explanation is that the patients with FHC receive earlier cancer screening, which leads to an earlier diagnosis (8,20,21). An early diagnosis could contribute to better quality of treatment and cure (22). Nevertheless, one cohort study suggested that there was no difference on tumor staging between the patients with FHC and without FHC, hence more clues are needed to explain the beneficial impact of FHC.

Of noting, the aforementioned studies enrolled the patients with great heterogeneity, such as various pathological types (NSCLC and small cell lung cancer) and treatment regimens (surgery, radiotherapy, chemotherapy). Given that surgery is the main curative treatment for lung cancer (1), it is important to reassess the prognostic impact of FHC in patients undergoing lung cancer surgery.

In this study, we found that FHC was an independent prognostic factor for survival of patients with LUSC in our study. Lee et al. enrolled 604 female never-smoking patients with LUAD after lung resection and found that the patients whose first-degree relatives had ever developing non-lung cancer would be exposed to higher risks of recurrence and death (10). However, the reason for detrimental effects of FHC on survival has not been elucidated clearly until now. We concluded four potential reasons: genetic differences, health-related behavior, shared environmental factors, and occurrence of second primary cancers. Firstly, given that in patients with NSCLC or other many cancers, an increasing number of significant germline mutations are identified in thoracic malignancy (23), prostate cancer (24), blood malignancy (25), and so forth. These germline mutations are more frequent in FHC group and might be associated with worse survival (26,27). Microsatellite instability and gene methylation level are also considered to be related to FHC and prognosis in colorectal cancer (28). However, few studies explore whether there is significant hereditary difference in lung cancer patients with FHC and if this is also associated with associated with long-term survival after surgery. Some studies analyzed the tumor genotype in lung cancer patients and found that epidermal growth factor receptor (EGFR) mutation (10,13) and anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1)/rearranged during transfection (RET) fusions (10) were significantly associated with FHC. A parametric genetic linkage analysis suggested that regions on chromosomes 12q, 7p, and 4q might increase the risk of occurrence of familial clustered lung cancers (29). Another worth noting concern is the clonal hematopoiesis mutations. It has been recently reported that FH-LC is a strong risk factor of clonal hematopoiesis mutations, and clonal hematopoiesis mutations may affect the immune response of the body to tumor (30). Secondly, patients with FHC might keep the same harmful living habits as their relatives with cancer. In this study, we found more smokers in the patients with FHC. Still as we discussed earlier, the change of living habits, for better or worse, would not uniform in the certain group of patients with FHC. Thirdly, Renkonen et al. (31) found that siblings and spouses of head and neck cancers patients were at a higher risk of developing head and neck cancers, denoting the significant role of shared environmental factors. Cluster onset of cancer might partly indicate common exposure to significant adverse factors, and might be associated with worse survival to some extent (31). Furthermore, recent publications are taking an interest in the association between FHC and second primary cancer. FHC has been reported to be significantly associated with occurrence of second primary cancers in patients with Hodgkin lymphoma (32), ovarian cancer (33), breast cancer (34), prostate cancer (35), and squamous cell skin cancer (36), and second primary cancers have deleterious effect on survival (37).

The impact of FHC on survival was different in the patients with LUAD and LUSC. We should note that there were more males in LUSC and more females in LUAD in our cohort. Furthermore, more early stage was in LUAD compared with that in LUSC. Female and early stage are regarded as good prognostic factors in lung cancer after surgery. In recent years, numerous studies have highlighted the distinct biological mechanisms underlying LUSC and LUAD are different, leading to diverse clinical prognosis (38,39). Chen et al. (38) identified a higher prevalence of TP53 mutations in LUSC patients. Meanwhile, a previous study demonstrated a significantly higher rate of TP53 mutations in patients with FHC compared to those without FHC (40). Hence, we speculate that the differential overlapping genes between LUAD/LUSC and the gene sets related to FHC might contribute to the disparate prognostic impact of FHC. In addition, smoking has been proved to be an independent risk factor for the onset of various cancers (41). Clinical evidence shows that compared with LUAD, the prognosis of LUSC are more closely related to smoking (42). Therefore, FHC may be more closely related to the prognosis of LUSC patients through its association with smoking environment. Nevertheless, there is currently a paucity of studies investigating the mechanism underlying the varied prognostic effects of FHC, necessitating further exploration. Moreover, we should be cautious when drawing conclusions regarding LUSC due to the limited sample size in our study.

Our findings might add to a growing body of evidence that suggests FHC plays a negative role in survival, not only in OS, but also in LCSS and PFS in LUSC patients after surgery. Clinicians need to pay more attention on family history of patients. Cancer screening for other family members is recommended in case of suspected familial aggregation (6). In addition, for patients with FHC, we should pay more attention to postoperative monitoring and timely treatment during follow-up. Lastly, our study revealed that FHC is an independent prognostic factor in LUSC, prompting the question of whether individuals with FHC, who are suitable for sublobar resection, might experience greater benefits from undergoing lobectomy instead. Moreover, there is a need for further investigation into the clinical significance of incorporating perioperative treatments for high-risk NSCLC patients, particularly those with FHC.

There are some inevitable limitations needed to be clarified. Firstly, this is a retrospective study, leading to some ineluctable bias. Secondly, sample size was limited when analyzing the impact of FHC on LUSC patients. Further, we could not thoroughly discuss the association between genetic changes and FHC and how family history affects survival. Lastly, the role of postoperative treatment, especially immunotherapy and targeted therapy, in this scenario should be further explored. Further experiment study is needed to explore the mechanisms behind the survival impact of FHC and confirm the hereditary effect of FHC.

Conclusions

In LUSC patients after surgery, FHC could detrimentally affect OS, LCSS and PFS. No significant impact was observed in LUAD patients after surgery. It is significant to intensify the follow-up for patients with FHC. More large cohort studies and experimental studies are required to further explore the role of FHC and its mechanism in cancer onset and progression.

Acknowledgments

Funding: This work was supported by National Natural Science Foundation of China (No. 82102968 to J.Z., No. 82302624 to M.L.).

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-349/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-349/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-349/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-349/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was approved by the Ethics Committee of West China Hospital of Sichuan University (No. 2022-641). The requirement for informed consent was waived due to the retrospective nature of this study. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. National Comprehensive Cancer Network. Non-small Cell Lung Cancer (Version 4.2024). Accessed April 15, 2024. Available online: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf
2. Cannon-Albright LA, Carr SR, Akerley W. Population-Based Relative Risks for Lung Cancer Based on Complete Family History of Lung Cancer. J Thorac Oncol 2019;14:1184-91. [Crossref] [PubMed]
3. Lin H, Huang YS, Yan HH, et al. A family history of cancer and lung cancer risk in never-smokers: A clinic-based case-control study. Lung Cancer 2015;89:94-8. [Crossref] [PubMed]
4. Toumazis I, Bastani M, Han SS, et al. Risk-Based lung cancer screening: A systematic review. Lung Cancer 2020;147:154-86. [Crossref] [PubMed]
5. Lin H, Zhang G, Zhang XC, et al. Germline variation networks in the PI3K/AKT pathway corresponding to familial high-incidence lung cancer pedigrees. BMC Cancer 2020;20:1209. [Crossref] [PubMed]
6. Chang GC, Chiu CH, Yu CJ, et al. Low-dose CT screening among never-smokers with or without a family history of lung cancer in Taiwan: a prospective cohort study. Lancet Respir Med 2024;12:141-52. [Crossref] [PubMed]
7. Zhang Y, Wang QL, Zeng E, et al. Analysis of Breast Cancer Family History, Estrogen Receptor Status, and Breast Cancer Outcomes in Sweden. JAMA Netw Open 2023;6:e2318053. [Crossref] [PubMed]
8. Pesola F, Eloranta S, Martling A, et al. Family history of colorectal cancer and survival: a Swedish population-based study. J Intern Med 2020;287:723-33. [Crossref] [PubMed]
9. Brook MN, Ní Raghallaigh H, Govindasami K, et al. Family History of Prostate Cancer and Survival Outcomes in the UK Genetic Prostate Cancer Study. Eur Urol 2023;83:257-66. [Crossref] [PubMed]
10. Lee Y, Jeon JH, Goh SH, et al. The clinical impact of family history of cancer in female never-smoker lung adenocarcinoma. Lung Cancer 2019;136:15-22. [Crossref] [PubMed]
11. Haraguchi S, Koizumi K, Mikami I, et al. Clinicopathological characteristics and prognosis of non-small cell lung cancer patients associated with a family history of lung cancer. Int J Med Sci 2012;9:68-73. [Crossref] [PubMed]
12. Ganti AK, Loberiza FR Jr, Kessinger A. Association of positive family history with survival of patients with lung cancer. Lung Cancer 2009;63:136-9. [Crossref] [PubMed]
13. Gaughan EM, Cryer SK, Yeap BY, et al. Family history of lung cancer in never smokers with non-small-cell lung cancer and its association with tumors harboring EGFR mutations. Lung Cancer 2013;79:193-7. [Crossref] [PubMed]
14. Nitadori J, Inoue M, Iwasaki M, et al. Association between lung cancer incidence and family history of lung cancer: data from a large-scale population-based cohort study, the JPHC study. Chest 2006;130:968-75. [Crossref] [PubMed]
15. Lissowska J, Foretova L, Dabek J, et al. Family history and lung cancer risk: international multicentre case-control study in Eastern and Central Europe and meta-analyses. Cancer Causes Control 2010;21:1091-104. [Crossref] [PubMed]
16. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007;370:1453-7. [Crossref] [PubMed]
17. Liu L, Che G, Pu Q, et al. A new concept of endoscopic lung cancer resection: Single-direction thoracoscopic lobectomy. Surg Oncol 2010;19:e71-7. [Crossref] [PubMed]
18. Li N, Shao K, Chen Z, et al. The impact of positive cancer family history on the clinical features and outcome of patients with non-small cell lung cancer. Fam Cancer 2011;10:331-6. [Crossref] [PubMed]
19. Isla D, Felip E, Viñolas N, et al. Lung Cancer in Women with a Family History of Cancer: The Spanish Female-specific Database WORLD07. Anticancer Res 2016;36:6647-53. [Crossref] [PubMed]
20. Ang M, Borg M, O'Callaghan ME, et al. Survival outcomes in men with a positive family history of prostate cancer: a registry based study. BMC Cancer 2020;20:894. [Crossref] [PubMed]
21. Lee M, Reilly M, Lindström LS, et al. Differences in survival for patients with familial and sporadic cancer. Int J Cancer 2017;140:581-90. [Crossref] [PubMed]
22. Jannot AS, Usel M, Bouchardy C, et al. Breast cancer family history leads to early breast cancer detection and optimal management. Cancer Causes Control 2017;28:921-8. [Crossref] [PubMed]
23. Farinea G, Crespi V, Listì A, et al. The Role of Germline Mutations in Thoracic Malignancies: Between Myth and Reality. J Thorac Oncol 2023;18:1146-64. [Crossref] [PubMed]
24. Cheng HH, Sokolova AO, Schaeffer EM, et al. Germline and Somatic Mutations in Prostate Cancer for the Clinician. J Natl Compr Canc Netw 2019;17:515-21. [Crossref] [PubMed]
25. Klco JM, Mullighan CG. Advances in germline predisposition to acute leukaemias and myeloid neoplasms. Nat Rev Cancer 2021;21:122-37. [Crossref] [PubMed]
26. Fan Z, Hu L, Ouyang T, et al. Germline mutation in DNA-repair genes is associated with poor survival in BRCA1/2-negative breast cancer patients. Cancer Sci 2019;110:3368-74. [Crossref] [PubMed]
27. Abe T, Blackford AL, Tamura K, et al. Deleterious Germline Mutations Are a Risk Factor for Neoplastic Progression Among High-Risk Individuals Undergoing Pancreatic Surveillance. J Clin Oncol 2019;37:1070-80. [Crossref] [PubMed]
28. Inamura K, Yamauchi M, Nishihara R, et al. Tumor LINE-1 methylation level and microsatellite instability in relation to colorectal cancer prognosis. J Natl Cancer Inst 2014;106:dju195. [Crossref] [PubMed]
29. Musolf AM, Moiz BA, Sun H, et al. Whole Exome Sequencing of Highly Aggregated Lung Cancer Families Reveals Linked Loci for Increased Cancer Risk on Chromosomes 12q, 7p, and 4q. Cancer Epidemiol Biomarkers Prev 2020;29:434-42. [Crossref] [PubMed]
30. Hong W, Li A, Liu Y, et al. Clonal Hematopoiesis Mutations in Patients with Lung Cancer Are Associated with Lung Cancer Risk Factors. Cancer Res 2022;82:199-209. [Crossref] [PubMed]
31. Renkonen S, Lee M, Mäkitie A, et al. Site-specific familial risk and survival of familial and sporadic head and neck cancer. Int J Cancer 2017;141:497-502. [Crossref] [PubMed]
32. Sud A, Thomsen H, Sundquist K, et al. Risk of Second Cancer in Hodgkin Lymphoma Survivors and Influence of Family History. J Clin Oncol 2017;35:1584-90. [Crossref] [PubMed]
33. Zheng G, Chattopadhyay S, Försti A, et al. Familial risks of second primary cancers and mortality in ovarian cancer patients. Clin Epidemiol 2018;10:1457-66. [Crossref] [PubMed]
34. Zheng G, Hemminki A, Försti A, et al. Second primary cancer after female breast cancer: Familial risks and cause of death. Cancer Med 2019;8:400-7. [Crossref] [PubMed]
35. Chattopadhyay S, Hemminki O, Försti A, et al. Impact of family history of cancer on risk and mortality of second cancers in patients with prostate cancer. Prostate Cancer Prostatic Dis 2019;22:143-9. [Crossref] [PubMed]
36. Chattopadhyay S, Zheng G, Hemminki A, et al. Influence of family history on risk of second primary cancers and survival in patients with squamous cell skin cancer. Br J Dermatol 2020;183:488-94. [Crossref] [PubMed]
37. Chattopadhyay S, Zheng G, Sud A, et al. Second primary cancers in non-Hodgkin lymphoma: Family history and survival. Int J Cancer 2020;146:970-6. [Crossref] [PubMed]
38. Chen JW, Dhahbi J. Lung adenocarcinoma and lung squamous cell carcinoma cancer classification, biomarker identification, and gene expression analysis using overlapping feature selection methods. Sci Rep 2021;11:13323. [Crossref] [PubMed]
39. Adib E, Nassar AH, Abou Alaiwi S, et al. Variation in targetable genomic alterations in non-small cell lung cancer by genetic ancestry, sex, smoking history, and histology. Genome Med 2022;14:39. [Crossref] [PubMed]
40. Sheng S, Xu Y, Guo Y, et al. Prevalence and clinical impact of TP53 germline mutations in Chinese women with breast cancer. Int J Cancer 2020;146:487-95. [Crossref] [PubMed]
41. Dai X, Gil GF, Reitsma MB, et al. Health effects associated with smoking: a Burden of Proof study. Nat Med 2022;28:2045-55. [Crossref] [PubMed]
42. Kawase A, Yoshida J, Ishii G, et al. Differences between squamous cell carcinoma and adenocarcinoma of the lung: are adenocarcinoma and squamous cell carcinoma prognostically equal? Jpn J Clin Oncol 2012;42:189-95. [Crossref] [PubMed]